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Khansari, Nemat. "The Future Direction of Cancer Vaccines: An Editorial." Vaccination Research – Open Journal 6, no. 1 (December 30, 2022): e1-e2. http://dx.doi.org/10.17140/vroj-6-e007.
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In the past, vaccines were defined as prophylactic entities. Today, there are two types of vaccines: prophylactic for prevention, and therapeutic for the treatment of infections or cancers. Therapeutic cancer vaccine, in fact, represents an option for active immunotherapy for the treatment of late-stage and/or prevention of recurrent diseases.1
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Bősze, Péter. "The first vaccine against cancer: the human papillomavirus vaccine." Orvosi Hetilap 154, no. 16 (April 2013): 603–18. http://dx.doi.org/10.1556/oh.2013.29593.
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The last 20 years is one of the most remarkable periods in the fight against cancer, with the realization that some human papillomaviruses are causally related to cancer and with the development of the vaccine against human papillomavirus infections. This is a historical event in medicine and the prophylactic human papillomavirus vaccines have provided powerful tools for primary prevention of cervical cancer and other human papillomavirus-associated diseases. This is very important as human papillomavirus infection is probably the most common sexually transmitted infection worldwide, and over one million women develop associated cancer yearly, which is about 5% of all female cancers, and half of them die of their disease. Cancers associated with oncogenic human papillomaviruses, mostly HPV16 and 18, include cervical cancer (100%), anal cancer (95%), vulvar cancer (40%), vaginal cancer (60%), penile cancer (40%), and oro-pharingeal cancers (65%). In addition, pre-cancers such as genital warts and the rare recurrent respiratory papillomatosis are also preventable by vaccination. Currently, the human papillomavirus vaccines have the potential to significantly reduce the burden of human papillomavirus associated conditions, including prevention of up to 70% of cervical cancers. Two prophylactic human papillomavirus vaccines are currently available worldwide: a bivalent vaccine (types 16 and 18), and a quadrivalent vaccine (types 6, 11, 16, and 18). Randomized controlled trials conducted on several continents during the last 10 years have demonstrated that these vaccines are safe without serious side effects; they are highly immunogenic and efficacious in preventing incident and persistent vaccine-type human papillomavirus infections, high grade cervical, vulvar and vaginal intraepithelial neoplasia and so on. In addition, the quadrivalent vaccine has been shown to prevent genital warts in women and men. The vaccine is most effective when given to human papillomavirus naive girls. The human papillomavirus vaccines have been incorporated into national immunization programs in 22 European countries. Routine vaccination is recommended for girls aged between 9 and 13 years and catch-up vaccination for females between 13 and 25 years of age. There is no excuse not to incorporate the vaccines into the Hungarian national immunization program. Albeit vaccination is expensive, it is cost-effective in the long run definitely. Anyway, vaccination is a matter of the specialty and the national health program, but not of business. We all are obliged to prevent human suffering. Orv. Hetil., 2013, 154, 603–618.
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Toft, Lars, Martin Tolstrup, Merete Storgaard, Lars Østergaard, and Ole S. Søgaard. "Vaccination against oncogenic human papillomavirus infection in HIV-infected populations: review of current status and future perspectives." Sexual Health 11, no. 6 (2014): 511. http://dx.doi.org/10.1071/sh14015.
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Background Men and women with HIV infection are at increased risk of developing cancers associated with human papillomavirus (HPV). The two licensed prophylactic HPV vaccines protect against de novo infection with HPV-16 and HPV-18, which cause the majority of HPV-associated cancers. Currently, no vaccine efficacy data are available for persons with HIV infection. Nevertheless, some countries have implemented specific HPV vaccination recommendations for HIV-positive populations. To specifically recommend prophylactic HPV vaccination in people with HIV, the vaccines must be safe and immunogenic in immunosuppressed people at a high risk of HPV infection. This review aims to summarise the current knowledge from published HPV vaccine trials in HIV-infected populations, to compile scheduled and ongoing HPV vaccine trials with HIV-positive study populations and to extrapolate the relevant knowledge about HPV vaccine efficacy in HIV-negative populations to an HIV context. Methods: The databases PubMed, Scopus and ClinicalTrials.gov were searched for peer-reviewed articles and scheduled or ongoing clinical HPV vaccine trials enrolling HIV-positive persons. Results: Current data indicate that prophylactic HPV vaccines are safe and immunogenic in different HIV-positive populations (children, female adolescents, adults). Increased immunogenicity has been reported in persons on antiretroviral therapy compared with antiretroviral-naïve persons, whereas no clear association has been found between CD4+ cell count at immunisation and vaccine response. Several scheduled and ongoing HPV vaccine trials aim to determine vaccine efficacy against disease endpoints in HIV-infected study populations. Conclusion: Prophylactic HPV vaccination appears safe, immunogenic and, by extrapolation, likely to reduce HPV-associated cancer development among persons with HIV infection.
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Lowy, Douglas R., and John T. Schiller. "Papillomaviruses: prophylactic vaccine prospects." Biochimica et Biophysica Acta (BBA) - Reviews on Cancer 1423, no. 1 (January 1999): M1—M8. http://dx.doi.org/10.1016/s0304-419x(98)00037-7.
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Dillner, Joakim, and Darron R. Brown. "Can genital-tract human papillomavirus infection and cervical cancer be prevented with a vaccine?" Expert Reviews in Molecular Medicine 6, no. 9 (April 19, 2004): 1–21. http://dx.doi.org/10.1017/s1462399404007653.
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Human papillomavirus (HPV) infection is the cause of squamous cell carcinoma of the uterine cervix. This causative relationship has provided the rationale and incentive for development of a prophylactic vaccine. Such a vaccine, if found to be effective, could reduce the need for cervical cancer screening and have a profound effect on the incidence of cervical and other anogenital cancers. This review begins by examining the basic biological and epidemiological principles relevant to the development of HPV preventative vaccines. It then summarises studies examining the use of vaccines to prevent HPV infection in animals and humans, and, finally, discusses some of the unanswered issues surrounding vaccine development against HPV infection and cervical cancer.
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Poole, I. Caroline Le, Hemamalini Bommiasamy, Maurizio Bocchetta, and W. Martin Kast. "Advances in prophylactic cancer vaccine research." Expert Review of Anticancer Therapy 3, no. 4 (August 2003): 537–45. http://dx.doi.org/10.1586/14737140.3.4.537.
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Sehnal, Borek, Daniel Driák, Monika Nipčová Džubáková, and Jiří Sláma. "Current data on the efficacy of prophylactic HPV vaccination in the primary prevention of cervical lesions." Česká gynekologie 87, no. 2 (April 26, 2022): 124–30. http://dx.doi.org/10.48095/cccg2022124.
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Objective: A review of current knowledge on the efficacy of HPV (human papillomavirus) HPV vaccination against pre-cancers and cervical cancer. Methods and results: HPV infection is probably the most common sexually transmitted disease and the cause of approximately 5% of all human cancers. Currently, three prophylactic vaccines against HPV infection are on the market: bivalent Cervarix, quadrivalent Gardasil (formerly Silgard) and nonavalent Gardasil9. The Czech Republic is one of the countries with a national vaccination program where HPV vaccination is covered by health insurance for girls and boys aged 13–14 years. Extensive scientific data on the efficacy of the vaccines clearly demonstrate significant efficacy against the development of cervical pre-cancers for all three vaccines. According to a high-certainty evidence of the Cochrane database, the efficacy of HPV vaccines against cervical intraepithelial neoplasia grade 2 or 3 associated with HPV 16, 18 compared with placebo in girls and women aged 15–26 is 99%. There is also moderate-certainty evidence that HPV vaccines reduce the risk of adenocarcinoma in situ for approximately 90% for the same population. Initial data also demonstrate a direct impact on reducing the incidence of invasive cervical cancer in vaccinated individuals. In addition, quadrivalent and nonavalent vaccines are highly effective in preventing genital warts. Conclusion: All three available prophylactic vaccines show high efficacy in preventing the development of cervical lesions. Effi cacy is highest against lesions caused by vaccine genotypes and the highest efficacy is achieved in the HPV naive population. Key words: human papillomavirus – HPV – vaccination – HPV vaccine – efficacy – cervical precancerous – cervical carcinoma
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Bencherif, Sidi, Dobrin Draganov, Sarah Lewin, Aileen Li, Roger Sands, Catia Verbeke, Glenn Dranoff, and David Mooney. "Immunologically active cryogels for breast cancer therapy (P4329)." Journal of Immunology 190, no. 1_Supplement (May 1, 2013): 126.1. http://dx.doi.org/10.4049/jimmunol.190.supp.126.1.
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Abstract Passive immunotherapy has become an effective adjunct for the treatment of HER2/neu-overexpressing breast cancers, as patients can respond well to monoclonal antibodies such as trastuzumab (anti-HER-2/neu antibody therapy). However, patients with late-stage disease, who often become immunosuppressed are unlikely to respond, motivating the development of new prophylactic vaccines. To this end, we have developed an injectable, polymer-based cryogel vaccine containing living, attenuated HER-2/neu-overexpressing breast cancer cells. The cryogel-based vaccine mimics key aspects of bacterial infection and directly controls immune-cell trafficking and activation in the body. This system provides a sustained release of GM-CSF to recruit host dendritic cells (DCs) to the porous material, and subsequently presents breast cancer antigens and TLR9 ligand CpG oligonucleotides to activate the resident DCs. Subcutaneous injection of the cryogel vaccines provide potent prophylactic protection against mammary cancer in mice, consistent with significantly higher titers of Her-2/neu-specific antibodies compared to the humoral responses induced by bolus injection of irradiated GM-CSF-secreting breast tumor cells. The cryogel-based vaccines induced a 70-fold increase in antibody production compared to untreated mice and 100% survival was achieved in vaccinated mice. The cryogel-based vaccines represent a promising tool for the development of novel active immunotherapeutic approaches to cancer.
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CASTLE, P. E., and M. MAZA. "Prophylactic HPV vaccination: past, present, and future." Epidemiology and Infection 144, no. 3 (October 2, 2015): 449–68. http://dx.doi.org/10.1017/s0950268815002198.
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SUMMARYHuman papillomavirus (HPV) is the necessary cause of cervical cancer, the fourth most common cancer and cause of cancer-related death in females worldwide. HPV also causes anal, vaginal, vulvar, penile, and oropharyngeal cancer. Prophylactic HPV vaccines based on recombinantly expressed virus-like particles have been developed. Two first-generation, U.S. Food and Drug Administration (FDA)-approved vaccines prevent infections and disease caused by HPV16 and HPV18, the two HPV genotypes that cause approximately 70% of cervical cancer, and one of these vaccines also prevents HPV6 and HPV11, the two HPV genotypes that cause 90% of genital warts. A next-generation vaccine, recently approved by the U.S. FDA, targets HPV16, HPV18, and five additional HPV genotypes that together causes approximately 90% of cervical cancer as well as HPV6 and HPV11. In clinical trials, these vaccines have shown high levels of efficacy against disease and infections caused by the targeted HPV genotypes in adolescent females and males and older females. Data indicate population effectiveness, and therefore cost effectiveness, is highest in HPV-naive young females prior to becoming sexually active. Countries that implemented HPV vaccination before 2010 have already experienced decreases in population prevalence of targeted HPV genotypes and related anogenital diseases in women and via herd protection in heterosexual men. Importantly, after more than 100 million doses given worldwide, HPV vaccination has demonstrated an excellent safety profile. With demonstrated efficacy, cost-effectiveness, and safety, universal HPV vaccination of all young, adolescent women, and with available resources at least high-risk groups of men, should be a global health priority. Failure to do so will result in millions of women dying from avertable cervical cancers, especially in low- and middle-income countries, and many thousands of women and men dying from other HPV-related cancers.
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Riolobos, Laura, Ekram Gad, Piper M. Treuting, Andrew Timms, and Mary Lenora Disis. "Development of a prophylactic vaccine for lung squamous cell carcinoma." Journal of Immunology 204, no. 1_Supplement (May 1, 2020): 169.9. http://dx.doi.org/10.4049/jimmunol.204.supp.169.9.
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Abstract High-grade bronchial dysplasia is a marker for high risk of lung squamous cell carcinoma (SCC). Cancer vaccines targeting dysplasia could prevent the progression to SCC and decrease lung cancer incidence in population at risk. In order to develop a vaccine to prevent lung SCC we need to identify antigens and epitopes within them able to elicit a potent Type I anti-tumor immune response. One caveat to develop a prophylactic vaccine targeting dysplasia is that driver mutations (neo-antigens) are not known. Many mutations appear late in lung cancer and are not shared between patients. However, upregulated non-mutated proteins are needed from the early stages of cancer to support the new proliferation requirements of the cells, are common between patients and are good candidates for a preventive vaccine. Type I CD4+ T cells (Th1) secreting interferon-gamma (IFN-g) are necessary for enhanced function of antigen presenting cells, epitope spreading and activation of cytotoxic CD8+ T cells. However, non-mutated tumor self-antigens frequently induce Type II CD4+ T cells (Th2), which secrete cytokines that inhibit the function of Th1 and CD8+ T cells. To develop a prophylactic lung cancer vaccine we have: (1) searched in public datasets genes that are upregulated in bronchial dysplasia and maintain upregulation in SCC; (2) used web based algorithms for class II epitope prediction followed by functional ELISPOT screening to identified epitopes eliciting IFN-g (Th1) and/or IL-10 (Th2) responses; (3) selected only the Th1 epitopes (excluding the Th2 epitopes) to evaluated efficacy of the vaccines in a chemically induced rodent model of SCC. Preliminary data shows that we can reduce dysplasia frequency in vaccinated mice treated with the carcinogen.
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Flemming, Alexandra. "Steps towards a prophylactic breast cancer vaccine." Nature Reviews Drug Discovery 9, no. 8 (August 2010): 594–95. http://dx.doi.org/10.1038/nrd3233.
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Zhao, Bao, Xin Li, Beinan Wang, Bin Gao, and Songdong Meng. "Prophylactic cancer vaccine, from concept to reality?" Chinese Science Bulletin 59, no. 10 (February 23, 2014): 944–49. http://dx.doi.org/10.1007/s11434-014-0176-y.
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Singh, Jagmohan, Wilbur B. Bowne, and Adam E. Snook. "Cancer Vaccines and Immunotherapy for Tumor Prevention and Treatment." Vaccines 9, no. 11 (November 9, 2021): 1298. http://dx.doi.org/10.3390/vaccines9111298.
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In this editorial, we highlight articles published in this Special Issue of Vaccines on “Cancer Vaccines and Immunotherapy for Tumor Prevention and Treatment”, recent developments in the field of cancer vaccines, and the potential for immunotherapeutic combinations in cancer care. This issue covers important developments and progress being made in the cancer vaccine field and possible future directions for exploring new technologies to produce optimal immune responses against cancer and expand the arena of prophylactic and therapeutic cancer vaccines for the treatment of this deadly disease.
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Campo, M. Saveria, and Richard B. S. Roden. "Papillomavirus Prophylactic Vaccines: Established Successes, New Approaches." Journal of Virology 84, no. 3 (November 11, 2009): 1214–20. http://dx.doi.org/10.1128/jvi.01927-09.
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ABSTRACT Vaccines against the human papillomaviruses (HPVs) most frequently associated with cancer of the cervix are now available. These prophylactic vaccines, based on virus-like particles (VLPs), are extremely effective, providing protection from infection in almost 100% of cases. However, the vaccines present some limitations: they are effective primarily against the HPV type present in the vaccine, are expensive to produce, and need a cold chain. Vaccines based on the minor capsid protein L2 have been very successful in animal models and have been shown to provide a good level of protection against different papillomavirus types. The potential of L2-based vaccines to protect against many types of HPVs is discussed.
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Liu, Margaret A. "Cancer vaccines." Philosophical Transactions of the Royal Society B: Biological Sciences 366, no. 1579 (October 12, 2011): 2823–26. http://dx.doi.org/10.1098/rstb.2011.0101.
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While vaccines are primarily thought of in terms of their use for prevention of infectious diseases, they can potentially be used to prevent or treat cancer. This manuscript explores the rationale for vaccines and immunotherapies for cancer from both the scientific and the global needs perspectives. Pathogens that are aetiologic agents of certain cancers provide perhaps the most obvious successful examples of the prophylactic utility of vaccines (such as the hepatitis B vaccine) to prevent not just the infectious disease (hepatitis), but the potential subsequent cancer (hepatocellular carcinoma). The use of monoclonal antibodies illustrates the effectiveness of the immune system for cancer therapy. In addition, the increased understanding of the role and mechanisms of the immune system in the processes of immune surveillance, as well as of its failure during immunosuppression, have yielded better insights into how to design cancer vaccines and immunotherapies. Examples of targets for cancer vaccines will be discussed, as will the challenges and few successes in this arena.
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Stump, Courtney T., Gregory Ho, Chenkai Mao, Frank A. Veliz, Veronique Beiss, Jennifer Fields, Nicole F. Steinmetz, and Steven Fiering. "Remission-Stage Ovarian Cancer Cell Vaccine with Cowpea Mosaic Virus Adjuvant Prevents Tumor Growth." Cancers 13, no. 4 (February 5, 2021): 627. http://dx.doi.org/10.3390/cancers13040627.
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Ovarian cancer is the deadliest gynecological malignancy. Though most patients enter remission following initial interventions, relapse is common and often fatal. Accordingly, there is a substantial need for ovarian cancer therapies that prevent relapse. Following remission generated by surgical debulking and chemotherapy, but prior to relapse, resected and inactivated tumor tissue could be used as a personalized vaccine antigen source. The patient’s own tumor contains relevant antigens and, when combined with the appropriate adjuvant, could generate systemic antitumor immunity to prevent relapse. Here, we model this process in mice to investigate the optimal tumor preparation and vaccine adjuvant. Cowpea mosaic virus (CPMV) has shown remarkable efficacy as an immunostimulatory cancer therapy in ovarian cancer mouse models, so we use CPMV as an adjuvant in a prophylactic vaccine against a murine ovarian cancer model. Compared to its codelivery with tumor antigens prepared in three other ways, we show that CPMV co-delivered with irradiated ovarian cancer cells constitutes an effective prophylactic vaccine against a syngeneic model of ovarian cancer in C57BL/6J mice. Following two vaccinations, 72% of vaccinated mice reject tumor challenges, and all those mice survived subsequent rechallenges, demonstrating immunologic memory formation. This study supports remission-stage vaccines using irradiated patient tumor tissue as a promising option for treating ovarian cancer, and validates CPMV as an antitumor vaccine adjuvant for that purpose.
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Liu, Margaret A. "DNA and mRNA Vaccines for Chronic Viral Infections and Cancer: Rationale, Mechanisms, and Progress." Cancers 14, no. 23 (November 29, 2022): 5874. http://dx.doi.org/10.3390/cancers14235874.
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Interest in the capabilities of nucleic acid vaccines, (DNA and mRNA vaccines) for both prophylactic and therapeutic uses have greatly increased following the successful deployment of two mRNA and, on a more limited scale, one DNA vaccine for COVID-19. In addition to targeting other pathogens for prophylactic vaccines, efforts are also being made towards using them for therapies for chronic infections and cancer. An examination of past and current successes for such therapies using other technologies with an emphasis on the immunological mechanisms will be provided followed by an assessment of the relevant characteristics of DNA and mRNA vaccines to predict their utility for therapies for chronic viral infections and cancer. Efforts and progress for these targets will be described.
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Chiriva, Maurizio, Yuefei Yu, Leonardo Mirandola, Marjorie Jenkins, Caroline Chapman, Martin Cannon, Everardo Cobos, and W. Martin Kast. "Effective prevention and therapy of ovarian cancer with sperm protein 17 vaccination (95.7)." Journal of Immunology 184, no. 1_Supplement (April 1, 2010): 95.7. http://dx.doi.org/10.4049/jimmunol.184.supp.95.7.
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Abstract Sperm protein (Sp17) is an attractive target for cancer vaccines because of its over-expression in primary and metastatic ovarian cancer (OC). Our studies suggest that a Sp17-based vaccine can induce an enduring defense against OC development in C57BL/6 mice with ID8 OC cells, following prophylactic and therapeutic treatments. Our results show that a SP17 protein based vaccine combined with CpG induced an effective CD8 mediated immune response against Sp17 protein. This is the first time that a mouse counterpart of a cancer testis antigen (Sp17) was shown to be expressed in an OC mouse model. and that vaccination against this antigen significantly controlled tumor growth . The CpG-adjuvanted vaccine are activating Th17 cells while inhibiting immunosuppressive T-reg cells, suggesting a reprogramming of active cellular-mediated response against Sp17-expressing tumor cells. Taken together, these results indicate that prophylactic and therapeutic vaccinations can induce long-standing protection against OC and delay tumor growth, suggesting that this strategy may provide additional treatments of human OC and the prevention of disease onset in women with a family history of OC.
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Donninger, Howard, Chi Li, John W. Eaton, and Kavitha Yaddanapudi. "Cancer Vaccines: Promising Therapeutics or an Unattainable Dream." Vaccines 9, no. 6 (June 18, 2021): 668. http://dx.doi.org/10.3390/vaccines9060668.
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The advent of cancer immunotherapy has revolutionized the field of cancer treatment and offers cancer patients new hope. Although this therapy has proved highly successful for some patients, its efficacy is not all encompassing and several cancer types do not respond. Cancer vaccines offer an alternate approach to promote anti-tumor immunity that differ in their mode of action from antibody-based therapies. Cancer vaccines serve to balance the equilibrium of the crosstalk between the tumor cells and the host immune system. Recent advances in understanding the nature of tumor-mediated tolerogenicity and antigen presentation has aided in the identification of tumor antigens that have the potential to enhance anti-tumor immunity. Cancer vaccines can either be prophylactic (preventative) or therapeutic (curative). An exciting option for therapeutic vaccines is the emergence of personalized vaccines, which are tailor-made and specific for tumor type and individual patient. This review summarizes the current standing of the most promising vaccine strategies with respect to their development and clinical efficacy. We also discuss prospects for future development of stem cell-based prophylactic vaccines.
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de Oliveira, Cristina Mendes, José Humberto T. G. Fregnani, and Luisa Lina Villa. "HPV Vaccine: Updates and Highlights." Acta Cytologica 63, no. 2 (2019): 159–68. http://dx.doi.org/10.1159/000497617.
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HPV is the most common sexually transmitted biological agent and is the cause of many conditions in men and women, including precancer lesions and cancer. Three prophylactic HPV vaccines targeting high-risk HPV types are available in many countries worldwide: 2-, 4- and 9-valent vaccines. All the 3 vaccines use recombinant DNA technology and are prepared from the purified L1 protein that self-assembles to form HPV type-specific empty shells. This non-systematic review aims to summarize the HPV epidemiology and the vaccine development to review the landmark trials of HPV vaccine, to present to most remarkable results from clinical trials and the real world, and to stress the challenges and the barriers for HPV vaccine implementation.
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Scholler, Nathalie, Khushboo Sharma, Catherine Yin, Kalika Kamat, Romaine Ingrid Fernando, Shizuko Sei, Robert H. Shoemaker, Paul L. Stein, and Lidia Sambucetti. "Development of a mesothelin-based prophylactic vaccine against ovarian cancer." Journal of Immunology 200, no. 1_Supplement (May 1, 2018): 181.23. http://dx.doi.org/10.4049/jimmunol.200.supp.181.23.
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Abstract Mesothelin is a tumor-associated antigen overexpressed in ovarian cancer and normally expressed by mesothelial linings. While mesothelin function remains to be fully elucidated, the lack of phenotype of mesothelin-knockout mice makes it plausible that mesothelin can safely serve as a vaccine target. We designed a new vaccination strategy based on mesothelin targeting with activation of type I IFN signaling via cyclic dinucleotides (CDN). Vaccines first combined human mesothelin protein with alum- vs. CDN-based adjuvants. C57Bl/6 mice received a priming immunization followed by 2 boosts; two weeks later, immunized mice were injected orthotopically with luciferase-transduced mouse ovarian cancer cells (Luc-ID8). More than 2/3 of the mesothelin/CDN-immunized mice were protected against invasive cancer and presented increased cytotoxic T cells (CTL) and plasmacytoid dendritic cells in spleens. Effector memory T cells were also increased and MDSC were profoundly decreased in peritoneal lavages after immunization with mesothelin +/− CDN compared with all the other groups. IFNγ ELISPOT assays performed with protected animal splenocytes stimulated with mesothelin peptides identified 2 immunogenic regions. We next tested a peptide-based subunit vaccine derived from mouse mesothelin sequence. Immunization and 2 boosts of 25-mer peptides with CDN were sufficient to mount an immune response against 2 overlapping mouse mesothelin peptides. Immunizations with peptide pools mapping in the immunogenic regions are currently assessed for protection against Luc-ID8 growth and progression. Peptide-based prophylactic vaccination against ovarian cancer may be possible in combination with adjuvants that trigger cellular immunity.
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Lunec, Anna. "Issues raised by prophylactic vaccine for cervical cancer." Lancet Oncology 6, no. 12 (December 2005): 923–24. http://dx.doi.org/10.1016/s1470-2045(05)70446-0.
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Richie, Jamaal, Numan Al-Rayyan, Robert Mitchell, John Eaton, and Kavitha Yaddanapudi. "Vaccination with Embryonic Stem Cells Protects against Lung Cancer." Journal of Immunology 196, no. 1_Supplement (May 1, 2016): 215.3. http://dx.doi.org/10.4049/jimmunol.196.supp.215.3.
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Abstract The antigenic similarity between tumors and embryos has been appreciated for many years and reflects the expression of embryonic gene products by cancer cells and/or cancer-initiating stem cells. Taking advantage of this similarity, we have tested a prophylactic lung cancer vaccine composed of allogeneic murine embryonic stem cells (ESC). Naïve C57BL/6 mice were vaccinated with ESC along with a source of granulocyte macrophage-colony stimulating factor (GM-CSF). Vaccinated mice were protected against subsequent challenge with implantable Lewis lung carcinoma (LLC). ESC-induced anti-tumor immunity was not due to a non-specific “allo-response” as vaccination with allogeneic murine embryonic fibroblasts did not protect against tumor outgrowth. Vaccine efficacy was associated with robust tumor-reactive primary and memory CD8+ T effector responses, Th1 cytokine response, higher intratumoral CD8+T effector/CD4+CD25+Foxp3+ T regulatory cell ratio, and reduced myeloid derived suppressor cells in the spleen. Prevention of tumorigenesis was found to require a CD8-mediated cytotoxic T lymphocyte (CTL) response because in vivo depletion of CD8+ T lymphocytes completely abrogated the protective effect of vaccination. To overcome the limitations of using whole ESC as a vaccine we modified our vaccination approach using exosomes derived from ESC. Our preliminary results thus far indicate that ESC-derived exosomes as a vaccine is effective against implantable lung tumors in mice. Further refinement of this novel vaccine strategy and identification of shared ESC/tumor antigens may lead to immunotherapeutic options for lung cancer patients and, potentially represent a step toward the development of prophylactic cancer vaccines.
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Paluch, Michał, Michał Tomkiewicz, Paweł Olko, Jakub Radulski, Piotr Sałata, Magda Żuchnik, Hugo Szczuraszek, Paulina Szczuraszek, Agnieszka Rybkowska, and Julia Tomkiewicz. "HPV virus as the main cause of cervical cancer, vaccination - literature review." Journal of Education, Health and Sport 13, no. 3 (February 12, 2023): 292–301. http://dx.doi.org/10.12775/jehs.2023.13.03.038.
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HPV infection is one of the most common viral infection of the female and male reproductive tract worldwide. Most of the human papillomavirus infections cause no symptoms and go away on their own. Some infections develop into persistent infection, which can lead to the development of cancer of the cervix, anogenital, oral cavity and pharynx.In this paper, we focused on cervical cancer, which is the second most common cancer in the world among women. More than 300,000 women died from this cancer in 2020. The invention and introduction of prophylactic HPV vaccines has played a significant role in reducing the number of viral infections, thus reducing the incidence of benign and malignant diseases caused by them and the mortality resulting from them. There are three vaccines on the pharmaceutical marketfor prevention of specific HPV infection. They are: a bivalent vaccine Cervarix, a tetravalent vaccine Gardasil and a nonavalent vaccine Gardasil 9. These vaccines are safe because they do not contain an attenuated virus particle, but their production is based on a virus-like particle of the main capsid protein L1-VLP. Gardasil 9 targets nine HPV types andcomparing to the other two vaccines it is the most effective at preventing the development of preinvasive cervical cancer. WHO recommends administering them to girls aged 9 to 14 in a two-dose schedule or from 15 years of age in a three-dose schedule. The side effects of the above-mentioned vaccines were mostly associated with a cutaneous reactions around the site of injection (pain, redness, swelling), and some people also experienced systemic symptoms such as a headache, a fever, vomiting, a dizziness, muscle pain and a diarrhea. The following article is an analysis of the current knowledge on the effectiveness and safety of prophylactic HPV vaccines based on publications available in the Pubmed and Google Scholar databases.
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Puri, Sonia, Naveen Krishan Goel, Veenal Chadha, and Praizy Bhandari. "Cancer vaccines: a newer front of immunotherapy." International Journal of Reproduction, Contraception, Obstetrics and Gynecology 7, no. 12 (November 26, 2018): 5214. http://dx.doi.org/10.18203/2320-1770.ijrcog20184998.
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Vaccines have been used as a promising instrument over the years to combat the dreadful communicable diseases. But now owing to epidemiological transition as the burden of non-communicable diseases has increased, efforts are now being made globally to use this weapon for non-communicable diseases like cancer. Cancer vaccines belong to a class of substances known as “biological response modifiers”. These work by stimulating or restoring the immune system’s ability to fight infections and disease. There are two broad types of cancer vaccines: Preventive (or prophylactic) vaccines and Treatment or therapeutic vaccines. Cancer treatment vaccines are made up of cancer cells, parts of cells or pure antigens. Sometimes a patient’s own immune cells are removed and exposed to these substances in the lab to create the vaccine. Cancer treatment vaccines differ from the vaccines that work against viruses. These vaccines try to get the immune system to mount an attack against cancer cells in the body. Instead of preventing disease, they are meant to get the immune system to attack a disease that already exists. Preventive vaccines are intended to prevent cancer from developing in healthy people. And in fact, many evidence-based studies have proven the decrease in morbidity and mortality in various cancers by usage of some of the vaccines like cervical cancer vaccine etc. The biggest challenges currently facing preventive anti-cancer vaccines are clinical, social, and economic in nature. This article is an effort to highlight the advances in various cancer vaccines, so done, to use them on preventive and therapeutic front.
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Truong, Hannah Hanh-Hong, Waleed M. Hussein, Tzu-Yu Liu, Zhongfan Jia, James W. Wells, Michael J. Monteiro, Mariusz Skwarczynski, and Mariusz Skwarczynski. "Self-Adjuvanting Peptide Vaccines Against Cervical Cancer." Vaccination Research – Open Journal 4, no. 1 (December 31, 2019): 21–29. http://dx.doi.org/10.17140/vroj-4-114.
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Background Cervical cancer is a common cause of cancer-related deaths in women worldwide, with a fatality rate second only to breast cancer. Human papillomaviruses (HPVs) are the main causative agents of cervical cancer, and are therefore obvious targets for vaccine development. Although two prophylactic HPV vaccines have been commercialized, therapeutic vaccines against HPVs have not been developed yet. Current vaccine technologies emphasize the power of small particles in targeting immune cells, and particles of 20-50 nm have been reported to induce optimal immune responses against a variety of pathogens and cancers. Methods We synthesized new nanoparticle-based vaccines against cervical cancer by using antigenic 8Qmin peptide epitope derived from HPV-16 E7 protein, a hydrophilic poly-(L-glutamic acid) (PGA) linker, and an 8-arm poly (tert-butyl acrylate) dendrimer-based delivery system (D8). Results Four different peptides containing 8Qmin and PGA of different lengths were successfully synthesized with high yield and purity. These were then conjugated to alkyne-functionalized D8 by copper-catalyzed alkyne-azide cycloaddition “click” reaction. The conjugates self-assembled into nanoparticles, with decreased particle size corresponding to a greater number of Glu units. The four vaccine candidates were tested in C57 black 6 (C57BL/6) mice bearing well-established (7-day-old) tumors to examine their therapeutic effects. Conclusion Interestingly, only one conjugate delayed tumor growth, and montanide adjuvanted antigen, used as a positive control, failed to demonstrate any therapeutic effect.
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Fardows, Jannatul, Naznin Nehar, Nurjahan Laskar, and Samsoon Nahar Joly. "Human Papilloma Virus Vaccine: Future of Cervical Cancer Prevention." Journal of Enam Medical College 6, no. 3 (October 20, 2016): 157–60. http://dx.doi.org/10.3329/jemc.v6i3.29683.
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Cervical cancer is a deadly cancer that clutches lives of the women in most of the cases due to lack of consciousness about the disease in the developing countries. It remains a threat which is second only to breast cancer in overall disease burden for women throughout the world. Cervical cancer is almost a preventable disease by prophylactic vaccine and routine screening. Both Cervarix and Gardasil vaccines have been effective in preventing persistent infection with targeted HPV types and in preventing cervical intraepithelial lesions. It is safe and nearly 100% effective if given before onset of sexual activity. This review article is aimed to explore different aspects of this vaccine as well as to develop awareness among health professionals of different disciplines.J Enam Med Col 2016; 6(3): 157-160
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Uche, Ifeanyi K., Brent Stanfield, Jared Rudd, Konstantin Kousoulas, and Paul J. Rider. "Abstract 3570: Prospects for personalized cancer vaccines: The oncolytic and immunotherapeutic HSV-1(VC2) virus expressing an ovalbumin (OVA) antigen elicits robust anti-OVA immune responses." Cancer Research 82, no. 12_Supplement (June 15, 2022): 3570. http://dx.doi.org/10.1158/1538-7445.am2022-3570.
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Abstract Cancers result from unique cellular transformation events resulting in the expression of cancer antigens that vary widely among different types of cancers. Ideally, a personalized cancer treatment approach needs to target specific cancer antigen. Efforts to induce specific immune responses against tumor associated antigens (TAAs) include the expression of TAAs through viral vectors capable of expressing multiple antigens. We have previously shown that the HSV-1(VC2) vaccine vector can induce potent antitumor immune responses utilizing the B16F10-derived syngeneic melanoma mouse model. To investigate whether heterologous antigens expressed by this vaccine vector could elicit potent immune responses, we generated the recombinant virus VC2-OVA that expresses the ovalbumin antigen (OVA) fused in-frame at the amino terminus of the viral VP26 protein. Western blot analysis of infected cells in cell culture showed efficient expression of the OVA-VP26 protein. The anti-tumor efficacy of the VC2-OVA virus was tested in the B16cOVA and E.G7-OVA mouse models that constitutively express the OVA antigen to test whether this vaccine can either prevent the formation of new tumors (prophylactic modality) or reduce tumor metastasis (therapeutic modality). In addition, we evaluated the differences between intradermal, subcutaneous, and intramuscular routes of vaccination with VC2-OVA. Treatment with VC2-OVA resulted in significant reduction of tumor formation and metastasis in both the prophylactic and therapeutic modalities. Importantly, the anti-tumor efficacy was dependent on the specific mouse tumor model. Further, we found that subcutaneous and intradermal was superior to intramuscular vaccination. The VC2 virus is available as a bacterial artificial chromosome allowing for the rapid isolation of recombinant VC2-derived virus expressing multiple tumor antigens. Therefore, these results demonstrate that the VC2 vaccine virus can be used to produce personalized cancer vaccines targeting specific TAAs. Citation Format: Ifeanyi K. Uche, Brent Stanfield, Jared Rudd, Konstantin Kousoulas, Paul J. Rider. Prospects for personalized cancer vaccines: The oncolytic and immunotherapeutic HSV-1(VC2) virus expressing an ovalbumin (OVA) antigen elicits robust anti-OVA immune responses [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 3570.
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Schreibelt, Gerty, Daniel Benitez-Ribas, Danita Schuurhuis, Annechien J. A. Lambeck, Maaike van Hout-Kuijer, Niels Schaft, Cornelis J. A. Punt, Carl G. Figdor, Gosse J. Adema, and I. Jolanda M. de Vries. "Commonly used prophylactic vaccines as an alternative for synthetically produced TLR ligands to mature monocyte-derived dendritic cells." Blood 116, no. 4 (July 29, 2010): 564–74. http://dx.doi.org/10.1182/blood-2009-11-251884.
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Abstract Currently dendritic cell (DC)–based vaccines are explored in clinical trials, predominantly in cancer patients. Murine studies showed that only maturation with Toll-like receptor (TLR) ligands generates mature DCs that produce interleukin-12 and promote optimal T-cell help. Unfortunately, the limited availability of clinical-grade TLR ligands significantly hampers the translation of these findings into DC-based vaccines. Therefore, we explored 15 commonly used preventive vaccines as a possible source of TLR ligands. We have identified a cocktail of the vaccines BCG-SSI, Influvac, and Typhim that contains TLR ligands and is capable of optimally maturing DCs. These DCs (vaccine DCs) showed high expression of CD80, CD86, and CD83 and secreted interleukin-12. Although vaccine DCs exhibited an impaired migratory capacity, this could be restored by addition of prostaglandin E2 (PGE2; vaccine PGE2 DCs). Vaccine PGE2 DCs are potent inducers of T-cell proliferation and induce Th1 polarization. In addition, vaccine PGE2 DCs are potent inducers of tumor antigen-specific CD8+ effector T cells. Finally, vaccine PGE2–induced DC maturation is compatible with different antigen-loading strategies, including RNA electroporation. These data thus identify a new clinical application for a mixture of commonly used preventive vaccines in the generation of Th1-inducing clinical-grade mature DCs.
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Hochnadel, Inga, Lisa Hoenicke, Nataliia Petriv, Lavinia Neubert, Elena Reinhard, Tatjana Hirsch, Juan Carlos Lopez Alfonso, et al. "Safety and efficacy of prophylactic and therapeutic vaccine based on live-attenuated Listeria monocytogenes in hepatobiliary cancers." Oncogene 41, no. 14 (February 16, 2022): 2039–53. http://dx.doi.org/10.1038/s41388-022-02222-z.
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AbstractPrimary liver cancer (PLC) comprising hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA) represents the third deadliest cancer worldwide with still insufficient treatment options. We have previously found that CD4 T helper 1 (Th1) response is indispensable for the protection against PLC. In the present research, we aimed to test the potent inducers of Th1 responses, live-attenuated Listeria monocytogenes ∆actA/∆inlB strain as preventive/therapeutic vaccine candidate in liver fibrosis, HCC, and CCA. Studies were performed using autochthonous models of HCC and CCA, highly reflecting human disease. L. monocytogenes ∆actA/∆inlB demonstrated strong safety/efficacy in premalignant and malignant liver diseases. The protective mechanism relied on the induction of strong tumor-specific immune responses that keep the development of hepatobiliary cancers under control. Combination therapy, comprising Listeria vaccination and a checkpoint inhibitor blockade significantly extended the survival of HCC-bearing mice even at the advanced stages of the disease. This is the first report on the safety and efficacy of Listeria-based vaccine in liver fibrosis, as well as the first proof of principle study on Listeria-based vaccines in CCA. Our study paves the way for the use of live-attenuated Listeria as safe and efficient vaccine and a potent inducer of protective immune responses in liver fibrosis and hepatobiliary malignancies.
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Qendro, Veneta, Mallika Ghosh, and Linda Shapiro. "Blocking CD13 in combination with a toll like receptor agonist increases the efficacy of cancer vaccine adjuvants." Journal of Immunology 198, no. 1_Supplement (May 1, 2017): 79.26. http://dx.doi.org/10.4049/jimmunol.198.supp.79.26.
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Abstract Vaccines have been an extraordinary tool in the fight against human disease. Recent cancer research has revealed promising results leading to approved cervical and prostate cancer vaccines. Despite the success, a major downfall of these vaccines remains poor immunogenicity. MPLA (monophosphorylated lipid A) is a synthetic analog of LPS that binds to TLR4 leading to activation of the adaptive immune response without triggering deleterious inflammatory consequences. As such, MPLA has recently been FDA approved as an adjuvant of the prophylactic vaccine against HPV-driven (Human Papilloma Virus) cervical cancer. However, this vaccine is limited to non-preexisting HPV cases while protecting against only two out of the dozen HPV strains that can potentially lead to cervical cancer. Pertinent to this subject, we have found that the absence of CD13 in antigen presenting cells (APCs), leads to increased TLR4 endocytosis and bias toward the same endocytic-signaling pathway triggered by MPLA. CD13 is a large, multifunctional cell surface peptidase constitutively expressed on all lineages of myeloid cells. We have previously shown that lack of CD13 increases tumor antigen uptake and presentation, resulting in enhanced activation of tumor-specific cytotoxic T cells. The combination of these facts has led to the intriguing possibility that blocking CD13 may amplify the efficacy of MPL as an adjuvant and ameliorate the efficacy of prophylactic and therapeutic cancer vaccines. Therefore, we hypothesize that CD13-blocking agents will act as dual-action adjuvants by enhancing MPL-TLR4 endocytosis, and as a delivery system through increased endocytic antigen uptake and subsequent cytotoxic T cell activation.
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Shen, Yingbin, Tianyao Hao, Shiyi Ou, Churan Hu, and Long Chen. "Applications and perspectives of nanomaterials in novel vaccine development." MedChemComm 9, no. 2 (2018): 226–38. http://dx.doi.org/10.1039/c7md00158d.
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Vo, Trinh Phuong, Gitika Panicker, Kimberly Braz-Gomes, Ashwin C. Parenky, Ira Rajbhandari, Mangalathu S. Rajeevan, Elizabeth R. Unger, Martin J. D’Souza, and Mohammad N. Uddin. "Enhanced Immunogenicity of Adjuvanted Microparticulate HPV16 Vaccines Administered via the Transdermal Route." Pharmaceuticals 15, no. 9 (September 9, 2022): 1128. http://dx.doi.org/10.3390/ph15091128.
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Human papillomavirus (HPV) causes cervical cancer among women and is associated with other anogenital cancers in men and women. Prophylactic particulate vaccines that are affordable, self-administered and efficacious could improve uptake of HPV vaccines world-wide. The goal of this research is to develop a microparticulate HPV16 vaccine for transdermal administration using AdminPatch® and assess its immunogenicity in a pre-clinical mouse model. HPV16 microparticles were prepared using a biocompatible polymer and characterized in terms of size, zeta potential, encapsulation efficiency and microparticle yield. Scanning and transmission electron microscopy were conducted to confirm particle image and to visualize the conformation of HPV16 vaccine particles released from microparticle formulation. In vivo studies performed to evaluate the potential of the microparticulate vaccine initiated a robust and sustained immune response. HPV16 IgG antibodies were significantly elevated in the microparticle group compared to antigen solutions administered by the transdermal route. Results show significant expansion of CD4+, CD45R, CD27 and CD62L cell populations in the vaccinated mice group, indicating the high efficacy of the microparticulate vaccine when administered via transdermal route. The findings of this study call attention to the use of minimally invasive, pain-free routes to deliver vaccine.
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Gonik, Bernard. "Strategies for Fostering HPV Vaccine Acceptance." Infectious Diseases in Obstetrics and Gynecology 2006 (2006): 1–4. http://dx.doi.org/10.1155/idog/2006/36797.
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Vaccines that protect against infection with the types of human papillomavirus (HPV) commonly associated with cervical cancer (HPV 16 and 18) and genital warts (HPV 6 and 11) are expected to become available in the near future. Because HPV vaccines are prophylactic, they must be administered prior to exposure to the virus, ideally during preadolescence or adolescence. The young age of the target vaccination population means that physicians, parents, and patients will all be involved in the decision-making process. Research has shown that parents and patients are more likely to accept a vaccine if it is efficacious, safe, reasonably priced, and recommended by a physician. Widespread education of physicians, patients, and parents about the risks and consequences of HPV infection and the benefits of vaccination will be instrumental for fostering vaccine acceptance.
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Medeiros, Rita, Susan Vaz, Teresa Rebelo, and Margarida Figueiredo-Dias. "Prevention of Human Papillomavirus Infection. Beyond Cervical Cancer: A Brief Review." Acta Médica Portuguesa 33, no. 3 (March 2, 2020): 198. http://dx.doi.org/10.20344/amp.12259.
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Introduction: Human papillomavirus is responsible for almost all cases of cervical cancer, an important portion of anogenital and oropharyngeal invasive and preinvasive lesions, as well as genital warts (condyloma acuminatum) and recurrent respiratory papillomatosis. Currently, three prophylactic vaccines against high-risk Human papillomavirus are commercialized in many countries worldwide. Methods: To this non-systematic review the authors searched in MEDLINE/PubMed for systematic reviews, meta-analysis and randomized controlled trials, published in the last six years, using the terms “HPV”, “non-cervical cancer” and “vaccine”. Non-cervical cancers caused by human papillomavirus are less common lesions. However, its incidence has been increasing, while cervical cancer has declined, due mainly to highly effective screening programs. There are no formal screening programs for non-cervical cancers, so universal vaccination could have an important impact. The preventive effect of the vaccine is mainly studied and established in relation to cervical cancer, although it has also been demonstrated in the development of vulvar and vaginal lesions. To date, the efficacy in preventing anal and oropharyngeal diseases related with human papillomavirus is uncertain due to scarce supporting data and low vaccination coverage in men. The prevalence of injuries and subsequent absolute benefit of vaccination is lower in men, but it provides an additional benefit to the herd immunity achieved with the vaccination of women.Conclusion: The total fraction of malignant and pre-malignant lesions attributed to Human papillomavirus genotypes contained in the nonavalent vaccine is significant in both women and men, which turns this vaccine into a great asset in terms of Public Health.
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Kraja, Shuajp. "Treating multiple cancers with the human anti-cancer heterologous bi-vaccine (TLNGIS)." Journal of Clinical Oncology 35, no. 15_suppl (May 20, 2017): e14633-e14633. http://dx.doi.org/10.1200/jco.2017.35.15_suppl.e14633.
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e14633 Background: Genomic segments of oncogenic viruses, when found inside healthy cell nuclei, can induce changes in the cell’s own genome during division, creating a transmittable change of genetic information. The new malignant cells thus created are recognized as foreign and destroyed by cellular immunity Thymuslymphocytes. Otherwise, unrecognised by the immune system and allowed to breed abnormally, such cells result in a malignant tumour mass, diagnosed as cancer. Based on this original theoretical explanation, we achieved the successful synthetization of a human heterologous anticancer Bi-Vaccine, further successfully confirming its prophylactic and curative abilities through the laboratory and clinic treatment of voluntary patients. Methods: Thymuslymphocytes, prepared though in indoor in vitro cultures and equipped with new and selective genetic information, acquire the ability to recognize cancerous cells as foreign cells, destroying them anywhere in the human body.The Bi-vaccine has been produced as the union of two vaccines: 1.the antitoxin, anti-tumour vaccine which destroys free toxins in the blood stream and in the pertinent cancerous cells; and 2.the thymus lymphocytic vaccine, equipped with new selective genetic information to destroy malignant tumour cells. Results: Thus the Bi-vaccine cures cancer until complete healing and protects subjects of all ages against the uncontrolled growth of malignant cells. The Bi-vaccine is produced in its live and dry state. Results: Over the years, there are treated and cured hundreds of voluntary patients with various forms of cancer. Successful healing in casses with advanced cancer (incurable casses). The Bi-vaccine is patented by European patents office-EP 1523991B1 as an anti-cancer vaccine "Human Heterologous Anti-Cancer Bi-Vaccine”. Conclusions: After more studies of several decades of all cases with different forms of cancer, treated with the “Bi-vaccine”has confirmed a complete success in various forms of cancer. The complementary (TLNGIS) cell to fight globally cancer. Prof. Dr. Shuajp Kraja, molecular biologist/Director of IIB Tirana, Albania Clinical trial information: EP523991 B1.
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Gillison, Maura L., Tatevik Broutian, Barry Graubard, Robert Pickard, Zhen-Yue Tong, Weihong Xiao, Lisa Kahle, and Anil Chaturvedi. "Impact of prophylactic human papillomavirus (HPV) vaccination on oral HPV infections among young adults in the U.S." Journal of Clinical Oncology 35, no. 15_suppl (May 20, 2017): 6003. http://dx.doi.org/10.1200/jco.2017.35.15_suppl.6003.
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6003 Background: The incidence of HPV-positive oropharyngeal cancers has risen in recent decades among US men. The potential impact of HPV vaccines on oral HPV infections has yet to be evaluated in efficacy-trials or surveillance studies. Methods: To evaluate the impact of prophylactic HPV vaccination on oral HPV infections in the US population, we conducted a cross-sectional study among men and women aged 18-33 years (n = 2,627) in the National Health and Nutrition Examination Survey, 2011-2014. We examined the effect of self-reported receipt of ≥1 vaccine dose on oral HPV infection (vaccine-types 16/18/6/11) prevalence among vaccinated vs. unvaccinated individuals. Additional outcomes included percent reduction in infection-prevalence among vaccinated individuals and population-level effectiveness of vaccination. Analyses accounted for the complex sampling design. Comparisons between vaccinated and unvaccinated individuals were conducted using binary logistic regression, with adjustment for age, gender, and race. Statistical significance was assessed using a quasi-score test. Results: During 2011-2014, 18.3% of the US population aged 18-33 years reported receipt of ≥1 HPV vaccine-dose prior to age 26 (29.2% in women and 6.9% in men; P< 0.001). The prevalence (population-weighted) of oral HPV16/18/6/11 infections was significantly reduced in vaccinated vs. unvaccinated individuals (0.11% vs. 1.61%; P= 0.008), corresponding to an estimated 88.2% (95%CI = 5.7%-98.5%) reduction in prevalence. Notably, oral HPV16/18/6/11 prevalence was significantly reduced in vaccinated vs. unvaccinated men (0.0% vs. 2.13%; P= 0.007). In contrast, prevalence for 33 non-vaccine HPV types was similar (3.98% vs. 4.74%; P= 0.24). Accounting for HPV vaccine-uptake, the population-level effectiveness of HPV vaccination on the burden of oral HPV16/18/6/11 infections was 17.0% overall, 25.0% in women and 6.9% in men. Conclusions: HPV vaccination substantially reduced vaccine-type oral HPV infection prevalence among young adults (ages 18-33 years) in the US population during 2011-2014. However, due to low vaccine uptake, population-level effectiveness was modest overall and particularly low in men.
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Fraillery, Dominique, David Baud, Susana Yuk-Ying Pang, John Schiller, Martine Bobst, Nathalie Zosso, Françoise Ponci, and Denise Nardelli-Haefliger. "Salmonella enterica Serovar Typhi Ty21a Expressing Human Papillomavirus Type 16 L1 as a Potential Live Vaccine against Cervical Cancer and Typhoid Fever." Clinical and Vaccine Immunology 14, no. 10 (August 8, 2007): 1285–95. http://dx.doi.org/10.1128/cvi.00164-07.
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ABSTRACT Human papillomavirus (HPV) vaccines based on L1 virus-like particles (VLPs) can prevent HPV-induced genital neoplasias, the precursors of cervical cancer. However, most cervical cancers occur in developing countries, where the implementation of expensive vaccines requiring multiple injections will be difficult. A live Salmonella-based vaccine could be a lower-cost alternative. We previously demonstrated that high HPV type 16 (HPV16)-neutralizing titers are induced after a single oral immunization of mice with attenuated Salmonella enterica serovar Typhimurium strains expressing a codon-optimized version of HPV16 L1 (L1S). To allow the testing of this type of vaccine in women, we constructed a new L1-expressing plasmid, kanL1S, and tested kanL1S recombinants of three Salmonella enterica serovar Typhi vaccine strains shown to be safe in humans, i.e., Ty21a, the actual licensed typhoid vaccine, and two highly immunogenic typhoid vaccine candidates, Ty800 and CVD908-htrA. In an intranasal mouse model of Salmonella serovar Typhi infection, Ty21a kanL1S was unique in inducing HPV16-neutralizing antibodies in serum and genital secretions, while anti-Salmonella responses were similar to those against the parental Ty21a vaccine. Electron microscopy examination of Ty21a kanL1S lysates showed that L1 assembled in capsomers and capsomer aggregates but not well-ordered VLPs. Comparison to the neutralizing antibody response induced by purified HPV16 L1 VLP immunizations in mice suggests that Ty21a kanL1S may be an effective prophylactic HPV vaccine. Ty21a has been widely used against typhoid fever in humans with a remarkable safety record. These finds encourage clinical testing of Ty21a kanL1S as a combined typhoid fever/cervical cancer vaccine with the potential for worldwide application.
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Firdaus, Farrhana Z., Stacey Bartlett, Waleed M. Hussein, Lantian Lu, Quentin Wright, Wenbin Huang, Ummey J. Nahar, et al. "Liposomal Formulations of a Polyleucine–Antigen Conjugate as Therapeutic Vaccines against Cervical Cancer." Pharmaceutics 15, no. 2 (February 10, 2023): 602. http://dx.doi.org/10.3390/pharmaceutics15020602.
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Human papilloma virus (HPV) is responsible for all cases of cervical cancer. While prophylactic vaccines are available, the development of peptide-based vaccines as a therapeutic strategy is still under investigation. In comparison with the traditional and currently used treatment strategies of chemotherapy and surgery, vaccination against HPV is a promising therapeutic option with fewer side effects. A peptide derived from the HPV-16 E7 protein, called 8Qm, in combination with adjuvants showed promise as a therapeutic vaccine. Here, the ability of polymerized natural amino acids to act as a self-adjuvating delivery system as a therapeutic vaccine was investigated for the first time. Thus, 8Qm was conjugated to polyleucine by standard solid-phase peptide synthesis and self-assembled into nanoparticles or incorporated in liposomes. The liposome bearing the 8Qm conjugate significantly increased mice survival and decreased tumor growth after a single immunization. Further, these liposomes eradicated seven-day-old well-established tumors in mice. Dendritic cell (DC)-targeting moieties were introduced to further enhance vaccine efficacy, and the newly designed liposomal vaccine was tested in mice bearing 11-day-old tumors. Interestingly, these DCs-targeting moieties did not significantly improve vaccine efficacy, whereas the simple liposomal formulation of 8Qm-polyleucine conjugate was still effective in tumor eradication. In summary, a peptide-based anticancer vaccine was developed that stimulated strong cellular immune responses without the help of a classical adjuvant.
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Wu, Di, Xiaoyu Yu, Jing Wang, Xu Hui, Yunxia Zhang, Yunlang Cai, Mulan Ren, Mei Guo, Fengshu Zhao, and Jun Dou. "Ovarian Cancer Stem Cells with High ROR1 Expression Serve as a New Prophylactic Vaccine for Ovarian Cancer." Journal of Immunology Research 2019 (March 17, 2019): 1–16. http://dx.doi.org/10.1155/2019/9394615.
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Tumor vaccines offer a number of advantages for cancer treatment. In the study, the vaccination with cancer stem cells (CSCs) with high expression of the type I receptor tyrosine kinase-like orphan receptor (ROR1) was evaluated in a murine model for the vaccine’s immunogenicity and protective efficacy against epithelial ovarian carcinoma (EOC). CD117+CD44+ CSCs were isolated from human EOC HO8910 cell line using a magnetic-activated cell sorting system; murine ID8 EOC suspension sphere cells, which are collectively known as cancer stem-like cells, were acquired from serum-free suspension sphere-forming culture. Mice were subcutaneously immunized with the repeat cycles of freezing and thawing whole HO8910 CD117+CD44+ CSCs and ID8 cancer stem-like cells, respectively, followed by a challenge with HO8910 or ID8 cells at one week after final vaccination. The results showed that the CSC vaccination significantly induced immunity against EOC growth and markedly prolonged the survival of EOC-bearing mice in the prophylactic setting compared with non-CSC vaccination. Flow cytometry showed significantly increased immunocyte cytotoxicities and remarkably reduced CSC counts in the CSC-vaccinated mice. Moreover, the protective efficacy against EOC was decreased when the ROR1 expression was downregulated by shRNA in CSC vaccines. The findings from the study suggest that CSC vaccines with high ROR1 expression were highly effective in triggering immunity against EOC in vaccinated mice and may serve as an effective vaccine for EOC immunoprophylaxis.
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Donkoh, Emmanuel T., Richard H. Asmah, Francis Agyemang-Yeboah, Ellis O. Dabo, and Edwin K. Wiredu. "Prevalence and Distribution of Vaccine-Preventable Genital Human Papillomavirus(HPV) Genotypes in Ghanaian Women Presenting for Screening." Cancer Control 29 (January 2022): 107327482210947. http://dx.doi.org/10.1177/10732748221094721.
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Background Cervical cancer is the most common gynaecologic cancer in Ghana where it is also the second most common cause of all female cancers. A number of vaccines are available to provide both individual and population-level protection against persistent infection with high-risk human papillomaviruses (HR-HPV) and reduce the burden of cervical cancer. Data on the epidemiology of vaccine-preventable papillomaviruses in Ghana is scant. Methods A cross-sectional observational study was implemented from May 2011 to November 2014 to understand the epidemiology of genital human papillomavirus (HPV) genotypes and cervical dysplasia in the Greater Kumasi area of Ghana. A nested multiplex polymerase chain reaction (NMPCR) assay incorporating degenerate E6/E7 consensus primers and type-specific primers was used for the detection and typing of eighteen (18) HPV genotypes among women who had never attended cervical screening prior to this study. Results The general prevalence of HPV infection in Kumasi was 37.2%. The age-standardized prevalence was 40.9% overall. The frequency of HR-HPV genotypes present in decreasing order were HPV-52, -56, -35, -18, -58, -68, -51, -39, -45, -16, -59, -33 and -31. Low-risk HPVs were also detected in the following order: HPV-42, -43, -66, -6/11 and -44. Conclusions The study shows that currently available prophylactic vaccines have the potential to be useful in the primary prevention of HPV infections in the country. This study strengthens the belief that prophylactic HPV vaccination could be a long-term strategy to reduce the burden of HPV infections and potentially reduce the burden of HPV-associated cancers and epithelial cell abnormalities among health-seeking women in Kumasi. Efforts to make vaccines available to young girls should be prioritized.
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Aleynick, Mark, Paul Peng, Linda Hammerich, Ranjan Upadhyay, Netonia Marshall, Judith Agudo, Michael Jay Yellin, et al. "Natural pattern-recognition-receptor agonists as adjuvants for in situ vaccination lymphoma immunotherapy." Journal of Clinical Oncology 36, no. 5_suppl (February 10, 2018): 123. http://dx.doi.org/10.1200/jco.2018.36.5_suppl.123.
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123 Background: In patients with low-grade lymphoma, in situ vaccination has yielded both partial and complete remissions in clinical trials. Though clinical responses have been observed with multiple pattern recognition receptor agonists (PRRa), the optimal immune stimulant is unknown. We hypothesize that natural PRRa, such as the attenuated pathogens or subunits found in common prophylactic vaccines, could target multiple PRR in a physiologically relevant context and lead to a more robust activation of dendritic cells (DCs) versus synthetic PRRa. Methods: 20 vaccines, including BCG, Typhim Vi, MMR-II, etc. were screened in vitro, where DC phenotype and function were evaluated by flow cytometry. Flt3L-mobilized DC ability to phagocytose, process, present, and cross-present soluble protein or tumor derived antigen, were assessed using CRISPR gene-edited, β2m(-/-) GFP-lymphoma cells and a novel GFP-specific (‘JEDI’) CD8 T cell system. Vaccine mechanism of immune activation was elucidated using a library of PRR-null macrophage cell lines. Potent vaccines were also evaluated in vivo in a Flt3L-primed in situ vaccination using the A20 murine lymphoma model. Results: Several vaccines induced robust DC activation and several showed significant increases in subsequent T cell activation, proliferation, and tumor killing, suggesting increased antigen processing and cross-presentation by DCs. Some vaccines, either as single agents or in combination, were significantly more effective than synthetic PRRa in activating DCs and inducing a T cell response. In vivo, vaccine combination therapies induced tumor regression in a majority of animals, suggesting synergistic immune activation. Conclusions: This data suggests prophylactic vaccines are effective clinical-grade DC activators and can be repurposed for use in the in situ vaccination maneuver, with immediate translation into the clinic. Additionally, by extensive in vitro evaluation in parallel with in vivo studies, this work aims to identify a predictive in vitro molecular immune signature that correlates closely with adjuvant efficacy in vivo.
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Heffernan, Margaret E., Suzanne M. Garland, and Mark A. Kane. "Global reduction of cervical cancer with human papillomavirus vaccines: insights from the hepatitis B virus vaccine experience." Sexual Health 7, no. 3 (2010): 383. http://dx.doi.org/10.1071/sh09134.
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Background: Worldwide, prophylactic vaccines against two major human cancers are now commercially available: hepatitis B virus (HBV) vaccines (first licensed in 1982) against primary hepatocellular carcinoma and human papillomavirus (HPV) vaccines (first licensed 2006) against cervical cancer. Initial implementation strategies for HBV vaccination were not successful in preventing disease in the community: it took 15 years for significant global reduction in the burden of this disease. Methods: We compare and contrast HBV vaccine experiences to challenges for successful global HPV vaccination strategies, and make recommendations accordingly. Results: Lessons from HBV immunisation for successful outcomes with HPV immunisation showed that several factors need to be met: (i) the engagement of key stakeholders in all aspects of planning and delivery of HPV vaccine strategies; (ii) understanding the specific characteristics of targeted population groups; (iii) global cooperation and support with WHO recommendations; (iv) Government supported mass immunization programs and cooperation between public and private entities; (v) affordable HPV vaccines for some regions; (vi) culturally appropriate and diverse public education programs in targeted health promotion strategies; (vii) pro-active health providers and parents in encouraging adolescents to undertake HPV vaccination; and (vii) eventual immunisation of infants. Conclusions: The key to success will be affordable, readily deliverable HPV vaccines to young girls as universal campaigns.
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Sellers, Rani S., Keith Nelson, Bindu Bennet, Jayanthi Wolf, Niraj Tripathi, Ronnie Chamanza, Marie-France Perron Lepage, Karissa Adkins, Sebastien Laurent, and Sean P. Troth. "Scientific and Regulatory Policy Committee Points to Consider*: Approaches to the Conduct and Interpretation of Vaccine Safety Studies for Clinical and Anatomic Pathologists." Toxicologic Pathology 48, no. 2 (October 8, 2019): 257–76. http://dx.doi.org/10.1177/0192623319875085.
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The design and execution of toxicology studies supporting vaccine development have some unique considerations relative to those supporting traditional small molecules and biologics. A working group of the Society of Toxicologic Pathology Scientific and Regulatory Policy Committee conducted a review of the scientific, technical, and regulatory considerations for veterinary pathologists and toxicologists related to the design and evaluation of regulatory toxicology studies supporting vaccine clinical trials. Much of the information in this document focuses on the development of prophylactic vaccines for infectious agents. Many of these considerations also apply to therapeutic vaccine development (such as vaccines directed against cancer epitopes); important differences will be identified in various sections as appropriate. The topics addressed in this Points to Consider article include regulatory guidelines for nonclinical vaccine studies, study design (including species selection), technical considerations in dosing and injection site collection, study end point evaluation, and data interpretation. The intent of this publication is to share learnings related to nonclinical studies to support vaccine development to help others as they move into this therapeutic area. [Box: see text]
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Sharma, Prashant, Na-Yoon Jang, Jae-Won Lee, Bum Chul Park, Young Keun Kim, and Nam-Hyuk Cho. "Application of ZnO-Based Nanocomposites for Vaccines and Cancer Immunotherapy." Pharmaceutics 11, no. 10 (September 26, 2019): 493. http://dx.doi.org/10.3390/pharmaceutics11100493.
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Engineering and application of nanomaterials have recently helped advance various biomedical fields. Zinc oxide (ZnO)-based nanocomposites have become one of the most promising candidates for biomedical applications due to their biocompatibility, unique physicochemical properties, and cost-effective mass production. In addition, recent advances in nano-engineering technologies enable the generation of ZnO nanocomposites with unique three-dimensional structures and surface characteristics that are optimally designed for in vivo applications. Here, we review recent advances in the application of diverse ZnO nanocomposites, with an especial focus on their development as vaccine adjuvant and cancer immunotherapeutics, as well as their intrinsic properties interacting with the immune system and potential toxic effect in vivo. Finally, we summarize promising proof-of-concept applications as prophylactic and therapeutic vaccines against infections and cancers. Understanding the nano-bio interfaces between ZnO-based nanocomposites and the immune system, together with bio-effective design of the nanomaterial using nano-architectonic technology, may open new avenues in expanding the biomedical application of ZnO nanocomposites as a novel vaccine platform.
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Mac, Michelle, and Cary A. Moody. "Epigenetic Regulation of the Human Papillomavirus Life Cycle." Pathogens 9, no. 6 (June 18, 2020): 483. http://dx.doi.org/10.3390/pathogens9060483.
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Persistent infection with certain types of human papillomaviruses (HPVs), termed high risk, presents a public health burden due to their association with multiple human cancers, including cervical cancer and an increasing number of head and neck cancers. Despite the development of prophylactic vaccines, the incidence of HPV-associated cancers remains high. In addition, no vaccine has yet been licensed for therapeutic use against pre-existing HPV infections and HPV-associated diseases. Although persistent HPV infection is the major risk factor for cancer development, additional genetic and epigenetic alterations are required for progression to the malignant phenotype. Unlike genetic mutations, the reversibility of epigenetic modifications makes epigenetic regulators ideal therapeutic targets for cancer therapy. This review article will highlight the recent advances in the understanding of epigenetic modifications associated with HPV infections, with a particular focus on the role of these epigenetic changes during different stages of the HPV life cycle that are closely associated with activation of DNA damage response pathways.
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Ni, Jing, Volker Schirrmacher, and Philippe Fournier. "Improvement of Anti-Tumor DNA Vaccination by Co-Immunization at a Distant Site with a Plasmid Encoding the Hemagglutinin-Neuraminidase Protein of Newcastle Disease Virus." Open Cancer Immunology Journal 3, no. 1 (November 11, 2010): 15–21. http://dx.doi.org/10.2174/1876401001003010015.
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DNA vaccine encoding tumor associated antigens (TAAs) is an attractive strategy for tumor vaccine development. But its efficacy to induce efficient anti-tumor immunity needs to be improved. In this study, we combined immunization with such a plasmid at the ear pinna site (i.e.) with co-immunization with another plasmid (pHN) encoding the Hemaglutinin-Neuraminidase (HN) protein of the NDV virus at a subcutaneous site. We first tested a prophylactic immunization protocol followed by subcutaneous challenge with the ESb-lacZ lymphoma expressing the -galactosidase protein as a surrogate tumor antigen. While i.e. vaccination with the placZ plasmid reduced tumor growth, the additional s.c. immunization with the pHN plasmid further improved this effect. We next tested a therapeutic tumor model based on the mammary carcinoma DA3-hEpCAM expressing the human EpCAM molecule. Efficient reduction of tumor growth was achieved by immunization of tumor-bearing mice with DNA plasmids encoding the human EpCAM gene only when it was combined with s.c. application of the pHN plasmid. A significantly better cross-protection against a second challenge with the parental DA3 tumor cells was only observed when mice were initially co-immunized with both plasmids. These results demonstrate that co-immunization of a plasmid encoding the HN protein of NDV and a DNA vaccine encoding a tumor antigen significantly reduced tumor growth in mouse tumor models employing both prophylactic and therapeutic vaccination strategies. These observations point towards the HN protein of NDV as a powerful molecular adjuvant for DNA vaccines.
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Morrow, Zachary, and John-Demian Sauer. "779 Inhibiting type-I interferon signaling promotes memory T-cell formation following immunization with Listeria anti-cancer vaccines." Journal for ImmunoTherapy of Cancer 9, Suppl 2 (November 2021): A814. http://dx.doi.org/10.1136/jitc-2021-sitc2021.779.
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BackgroundThe aspiration of cancer immunotherapy is to generate large numbers of highly functional anti-tumor CD8+ T-cells. We and others have optimized Listeria monocytogenes as a powerful anti-cancer vaccine platform to drive such T-cell responses. Early clinical trial data suggest the number of T-cells generated correlates with efficacy, demanding an understanding of the factors that dictate vaccine-induced T-cell responses. The CD8+ T-cell response is intimately linked to magnitude and quality of the innate immune response triggered by vaccines. Listeria-based vaccines activate numerous innate pathways and can be engineered to hyper- or hypo-induce these pathways. We sought to understand how modulating innate immunity would impact vaccine efficacy.MethodsTo dissect the impact of type I interferon signaling and the inflammasomes on L. monocytogenes induced T-cell responses, we immunized IFNAR-/-, Caspase1/11-/-, and novel IFNAR-/-Caspase1/11-/- double knockouts mice we generated for this study. CD8+ T-cell responses were assessed at the peak T-cell response, after contraction and memory formation, and after rechallenge. The phenotype and magnitude of CD8+ T-cells was assessed at each stage, and functional outcomes were assessed by measuring protection from reinfection by wild-type Listeria.ResultsIFNAR-/- mice developed the largest number of CD8+ T-cells during the peak primary response contradicting the dogma that Type-I Interferon promotes robust CD8+ T-cell responses. Caspase1/11-/- mice were not significantly different from wild-type mice. The frequency of short-lived effector cells (assessed by expression of CD127 and KLRG1) was no different between wild-type and IFNAR-/- mice, however we observed more than twice as many memory precursor cells at the peak CD8+ T-cell response. These findings extend to the memory and recall stage with more antigen-specific T-cells observed after contraction and upon rechallenge. Finally, IFNAR-/- mice are remarkably more protected from wild-type Listeria rechallenge than their counterparts after immunization demonstrating the efficacy of the increased memory T-cell pool. Data are representative of at least two independent replicates with at least 5 mice per group and significance was assessed by one-way ANOVA with *p<0.05.ConclusionsWe demonstrated that type-I interferon signaling deficiency leads to enhanced prophylactic vaccine efficacy through increased memory T-cell formation. Ultimately, for patients with slow growing tumors or with high-risk mutations, prophylactic tumor vaccines could elicit life-long protection from disease. Importantly, increased memory precursor T-cell abundance did not come at the expense of short-lived effectors leaving open the possibility that blocking Type-I IFN could potentiate lasting immunological memory in both the therapeutic and prophylactic setting.
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Natunen, Kari, Johannes Lehtinen, Proscovia Namujju, John Sellors, and Matti Lehtinen. "Aspects of Prophylactic Vaccination against Cervical Cancer and Other Human Papillomavirus-Related Cancers in Developing Countries." Infectious Diseases in Obstetrics and Gynecology 2011 (2011): 1–10. http://dx.doi.org/10.1155/2011/675858.
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Cervical cancer and other human papillomavirus- (HPV-) related cancers are preventable, but preventive measures implemented in developing countries and especially in low-income rural regions have not been effective. Cervical cancer burden derived from sexually transmitted HPV infections is the heaviest in developing countries, and a dramatic increase in the number of cervical cancer cases is predicted, if no intervention is implemented in the near future. HPV vaccines offer an efficient way to prevent related cancers. Recently implemented school-based HPV vaccination demonstration programmes can help tackle the challenges linked with vaccine coverage, and access to vaccination and health services, but prevention strategies need to be modified according to regional characteristics. In urban regions WHO-recommended vaccination strategies might be enough to significantly reduce HPV-related disease burden, but in the rural regions additional vaccination strategies, vaccinating both sexes rather than only females when school attendance is the highest and applying a two-dose regime, need to be considered. From the point of view of both public health and ethics identification of the most effective prevention strategies is pivotal, especially when access to health services is limited. Considering cost-effectiveness versus justice further research on optional vaccination strategies is warranted.
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Vieira, Jéssica Ferreira, Eddie Fernando Candido Murta, and Márcia Antoniazi Michelin. "Prophylactic dendritic cell vaccination in antitumor immune response and tumor growth in a breast cancer mouse model." Research, Society and Development 10, no. 13 (October 5, 2021): e100101320905. http://dx.doi.org/10.33448/rsd-v10i13.20905.
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Dendritic cell vaccines have demonstrated promising results for poorly immunogenic tumors, which may promote the generation of better immune responses in the tumor microenvironment. However, the vaccine has little been evaluated as a prophylactic option. Therefore, this study evaluates the influence of prophylactic dendritic cell vaccination on the antitumor immune response in the tumor microenvironment and on tumor growth, in an experimental model with breast cancer induced by 4T1. Therefore, Balb/c mice were separated into a vaccinated group and an unvaccinated group. Dendritic cell vaccine was differentiated and matured ex vivo from bone marrow. During the experimental period, the tumor volumes were checked periodically. The tumors were evaluated for immune cells (helper T lymphocytes and cytotoxic T lymphocytes), helper T cells (Th1, Th2, Th17, and Treg), TNF-α, and IFN-γ synthesis by Th1 and cytotoxic T lymphocytes. The vaccinated group had decreased tumor volume (14.0, 0-131.7) compared to the unvaccinated group (89.59, 0.1250-459.6) (p=0.0421). The Th1, Th2, Th17, Treg, cytotoxic T subtypes, including TNF-α and IFN-γ produced by Th1 and T cytotoxic, showed a significant increase in the vaccinated group, as did the balance of Th1/Th2 and Th1/Treg. The results showed that prophylactic vaccination with dendritic cells showed a considerable antitumor effect in the studied model by promoting an increase in the activation of important cells in the immune response and a reduction in tumor volume. The data provide evidence for timely activation of immune surveillance in the absence of tumor burden.