Journal articles: 'Antibody response to HIV'

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Kim, H. N., R. D. Harrington, H. M. Crane, S. Dhanireddy, T. H. Dellit, and D. H. Spach. "Hepatitis B vaccination in HIV-infected adults: current evidence, recommendations and practical considerations." International Journal of STD & AIDS 20, no. 9 (September 2009): 595–600. http://dx.doi.org/10.1258/ijsa.2009.009126.

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Immunization with hepatitis B (HBV) vaccine is recommended for all HIV-infected individuals without immunity to HBV. This patient population, however, has relatively poor HBV vaccine responses. Factors associated with this impaired HBV vaccine response in HIV-infected individuals may include older age, uncontrolled HIV replication, and low nadir CD4 cell count. Postvaccination testing for HBV surface antibody is recommended and vaccine non-responders should undergo repeat immunization with a full series. The benefit of double dosage, the appropriate strategy for HIV-infected patients with isolated HBV core antibody and the timing and number of vaccinations in persons with advanced immunosuppression on highly active antiretroviral therapy remain controversial areas.

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Overbaugh, J., and L. Morris. "The Antibody Response against HIV-1." Cold Spring Harbor Perspectives in Medicine 2, no. 1 (November 1, 2011): a007039. http://dx.doi.org/10.1101/cshperspect.a007039.

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BORMAN, STU. "HIV vaccine produces broad antibody response." Chemical & Engineering News 77, no. 3 (January 18, 1999): 15. http://dx.doi.org/10.1021/cen-v077n003.p015.

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Ye, Ling, Zhiyuan Wen, Ke Dong, Lei Pan, Zhigao Bu, Richard W. Compans, Huizhong Zhang, and Chinglai Yang. "Immunization with a Mixture of HIV Env DNA and VLP Vaccines Augments Induction of CD8 T Cell Responses." Journal of Biomedicine and Biotechnology 2010 (2010): 1–11. http://dx.doi.org/10.1155/2010/497219.

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The immune response induced by immunization with HIV Env DNA and virus-like particle (VLP) vaccines was investigated. Immunization with the HIV Env DNA vaccine induced a strong CD8 T cell response but relatively weak antibody response against the HIV Env whereas immunization with VLPs induced higher levels of antibody responses but little CD8 T cell response. Interestingly, immunization with a mixture the HIV Env DNA and VLP vaccines induced enhanced CD8 T cell and antibody responses. Further, it was observed that the mixing of DNA and VLP vaccines during immunization is necessary for augmenting induction of CD8 T cell responses and such augmentation of CD8 T cell responses was also observed by mixing the HIV Env DNA vaccine with control VLPs. These results show that immunization with a mixture of DNA and VLP vaccines combines advantages of both vaccine platforms for eliciting high levels of both antibody and CD8 T cell responses.

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Kadelka, Claus, Thomas Liechti, Hanna Ebner, Merle Schanz, Peter Rusert, Nikolas Friedrich, Emanuel Stiegeler, et al. "Distinct, IgG1-driven antibody response landscapes demarcate individuals with broadly HIV-1 neutralizing activity." Journal of Experimental Medicine 215, no. 6 (May 24, 2018): 1589–608. http://dx.doi.org/10.1084/jem.20180246.

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Understanding pathways that promote HIV-1 broadly neutralizing antibody (bnAb) induction is crucial to advance bnAb-based vaccines. We recently demarcated host, viral, and disease parameters associated with bnAb development in a large HIV-1 cohort screen. By establishing comprehensive antibody signatures based on IgG1, IgG2, and IgG3 activity to 13 HIV-1 antigens in 4,281 individuals in the same cohort, we now show that the same four parameters that are significantly linked with neutralization breadth, namely viral load, infection length, viral diversity, and ethnicity, also strongly influence HIV-1–binding antibody responses. However, the effects proved selective, shaping binding antibody responses in an antigen and IgG subclass–dependent manner. IgG response landscapes in bnAb inducers indicated a differentially regulated, IgG1-driven HIV-1 antigen response, and IgG1 binding of the BG505 SOSIP trimer proved the best predictor of HIV-1 neutralization breadth in plasma. Our findings emphasize the need to unravel immune modulators that underlie the differentially regulated IgG response in bnAb inducers to guide vaccine development.

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Stratov, Ivan, Amy Chung, and Stephen J. Kent. "Robust NK Cell-Mediated Human Immunodeficiency Virus (HIV)-Specific Antibody-Dependent Responses in HIV-Infected Subjects." Journal of Virology 82, no. 11 (March 19, 2008): 5450–59. http://dx.doi.org/10.1128/jvi.01952-07.

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ABSTRACT Antibody-dependent cellular cytotoxicity (ADCC) is a potentially effective adaptive immune response to human immunodeficiency virus (HIV) infection. The study of ADCC responses has been hampered by the lack of simple methods to quantify these responses and map effective epitopes. We serendipitously observed that standard intracellular cytokine assays on fresh whole blood from a cohort of 26 HIV-infected subjects identified non-T lymphocytes expressing gamma interferon (IFN-γ) in response to overlapping linear peptides spanning HIV-1 proteins. The effector cells were CD3− CD4− CD8− CD14− CD2+ CD56+/− NK lymphocytes and degranulated granzyme B and perforin in response to antigen stimulation. Serum transfer assays demonstrated that the specific response was mediated by immunoglobulin G. Fresh blood samples from half of the HIV-infected cohort demonstrated robust HIV peptide-specific IFN-γ expression by NK cells, predominately to Env, Pol, and Vpu HIV-1 proteins. Responses were readily mapped to define minimal epitopes utilizing this assay. Antibody-dependent, HIV-specific NK cell recognition, involving components of both innate and adaptive immune systems, represents a potentially effective immune response to induce by vaccination.

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Zhou, Yinggao, Kuan Yang, Kai Zhou, and Chunling Wang. "Optimal Treatment Strategies for HIV with Antibody Response." Journal of Applied Mathematics 2014 (2014): 1–13. http://dx.doi.org/10.1155/2014/685289.

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Numerical analysis and optimization tools are used to suggest improved therapies to try and cure HIV infection. An HIV model of ordinary differential equation, which includes immune response, neutralizing antibodies, and multidrug effects, is improved. For a fixed time, single-drug and two-drug treatment strategies are explored based on Pontryagin’s maximum principle. Using different combinations of weight factor pairs combining with special upper-bound pairs for controls, nine types of treatment policies are determined and different therapy effects are numerically simulated with a gradient projection method. Some strategies are effective, but some strategies are not particularly helpful for the therapy of HIV/AIDS. Comparing the effective treatment strategies, we find a more appropriate strategy with maximizing the number of uninfected CD4+T-cells and minimizing the number of active virus.

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Crothers, Kristina, Kieran R. Daly, David Rimland, Matthew Bidwell Goetz, Cynthia L. Gibert, Adeel A. Butt, Amy C. Justice, Kpandja Djawe, Linda Levin, and Peter D. Walzer. "Decreased Serum Antibody Responses to RecombinantPneumocystisAntigens in HIV-Infected and Uninfected Current Smokers." Clinical and Vaccine Immunology 18, no. 3 (December 29, 2010): 380–86. http://dx.doi.org/10.1128/cvi.00421-10.

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ABSTRACTSerologic studies can provide important insights into the epidemiology and transmission ofPneumocystis jirovecii. Exposure toP. jiroveciican be assessed by serum antibody responses to recombinant antigens from the major surface glycoprotein (MsgC), although factors that influence the magnitude of the antibody response are incompletely understood. We determined the magnitudes of antibody responses toP. jiroveciiin comparison to adenovirus and respiratory syncytial virus (RSV) in HIV-infected and uninfected patients and identified predictors associated with the magnitude of the response. We performed a cross-sectional analysis using serum samples and data from 153 HIV-positive and 92 HIV-negative subjects enrolled in a feasibility study of the Veterans Aging Cohort 5 Site Study (VACS 5). Antibodies were measured using an enzyme-linked immunosorbent assay (ELISA). Independent predictors of antibody responses were determined using multivariate Tobit regression models. The results showed that serum antibody responses toP. jiroveciiMsgC fragments were significantly and independently decreased in current smokers. Antibodies toP. jiroveciialso tended to be lower with chronic obstructive pulmonary disease (COPD), hazardous alcohol use, injection drug use, and HIV infection, although these results were not statistically significant. These results were specific toP. jiroveciiand did not correlate with adenovirus. Antibody responses to RSV were in the inverse direction. Thus, current smoking was independently associated with decreasedP. jiroveciiantibody responses. Whether smoking exerts an immunosuppressive effect that affects theP. jiroveciiantibody response, colonization, or subsequent risk for disease is unclear; prospective, longitudinal studies are needed to evaluate these findings further.

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Tannig, Pierre, Antonia Sophia Peter, Dennis Lapuente, Stephan Klessing, Dominik Damm, Matthias Tenbusch, Klaus Überla, and Vladimir Temchura. "Modulation of Vaccine-Induced HIV-1-Specific Immune Responses by Co-Electroporation of PD-L1 Encoding DNA." Vaccines 8, no. 1 (January 14, 2020): 27. http://dx.doi.org/10.3390/vaccines8010027.

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The importance of a balanced TH1/TH2 humoral immune response against the HIV-1 envelope protein (Env) for antibody-mediated HIV-1 control is increasingly recognized. However, there is no defined vaccination strategy to raise it. Since immune checkpoints are involved in the induction of adoptive immunity and their inhibitors (monoclonal antibodies) are licensed for cancer therapy, we investigated the effect of checkpoint blockade after HIV-1 genetic vaccination on enhancement and modulation of antiviral antibody responses. By intraperitoneal administration of checkpoint antibodies in mice we observed an induction of anti-drug antibodies which may interfere with immunomodulation by checkpoint inhibitors. Therefore, we blocked immune checkpoints locally by co-electroporation of DNA vaccines encoding the active soluble ectodomains of programmed cell death protein-1 (PD-1) or its ligand (PD-L1), respectively. Plasmid-encoded immune checkpoints did not elicit a detectable antibody response, suggesting no interference with their immunomodulatory effects. Co-electroporation of a HIV-1 DNA vaccine formulation with soluble PD-L1 ectodomain increased HIV-1 Env-specific TH1 CD4 T cell and IgG2a antibody responses. The overall antibody response was hereby shifted towards a more TH1/TH2 balanced subtype pattern. These findings indicate that co-electroporation of soluble checkpoint ectodomains together with DNA-based vaccines has modulatory effects on vaccine-induced immune responses that could improve vaccine efficacies.

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Mascola, John. "Defining the Protective Antibody Response for HIV-1." Current Molecular Medicine 3, no. 3 (May 1, 2003): 209–16. http://dx.doi.org/10.2174/1566524033479799.

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Cohen, J. "Novel Antibody Response May Explain HIV Vaccine Success." Science 333, no. 6049 (September 15, 2011): 1560. http://dx.doi.org/10.1126/science.333.6049.1560.

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Richardson, Simone I., and Penny L. Moore. "The antibody response in HIV-1-infected donors." Current Opinion in HIV and AIDS 14, no. 4 (July 2019): 233–39. http://dx.doi.org/10.1097/coh.0000000000000559.

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Gowda, Charitha, Noah McKittrick, Deborah Kim, Rosemarie A. Kappes, Vincent Lo Re, and Pablo Tebas. "Obesity Is Not Associated with Impaired Immune Response to Influenza Vaccination in HIV-Infected Persons." AIDS Research and Treatment 2015 (2015): 1–7. http://dx.doi.org/10.1155/2015/653840.

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Introduction. HIV-infected individuals demonstrate lower immunogenicity to the influenza vaccine, despite immunologic and virologic control of HIV infection. Obesity has been previously shown to be associated with diminished antibody responses to other vaccines in HIV-uninfected persons. However, no studies have examined if obesity is associated with diminished protective immune response to influenza vaccination among HIV-infected persons on antiretroviral therapy (ART).Methods. We performed a retrospective analysis of immunogenicity data from a clinical trial of inactivated, trivalent influenza vaccine. The primary endpoint was the proportion of participants with seroconversion, defined as >4-fold increase in anti-hemagglutinin antibody titers after vaccination. Secondary endpoints were the proportion of participants with seroprotection (defined as antibody titers of ≥1 : 40) and geometric mean hemagglutination inhibition antibody titers.Results. Overall, 48 (27%) participants were obese (body mass index ≥ 30 kg/m2). Seroconversion rates were comparable between obese and nonobese subjects for all three vaccine strains. Further, postvaccination geometric mean titers did not differ by body mass index category.Conclusion. Obesity was not associated with diminished antibody response to influenza vaccination in a sample of healthy HIV-infected persons.

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Touloumi, Giota, Argiro Karakosta, Vana Sypsa, Ioanna Petraki, Olga Anagnostou, Agis Terzidis, Niki Maria Voudouri, et al. "Design and Development of a Viral Hepatitis and HIV Infection Screening Program (Hprolipsis) for the General, Greek Roma, and Migrant Populations of Greece: Protocol for Three Cross-Sectional Health Examination Surveys." JMIR Research Protocols 9, no. 1 (January 31, 2020): e13578. http://dx.doi.org/10.2196/13578.

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Background Although infectious diseases are globally on the decline, they remain a major global public health problem. Among them, the hepatitis B virus (HBV) or hepatitis C virus (HCV) and HIV infection are of primary interest. Valid prevalence data on these infections are sparse in Greece, especially for vulnerable populations. Objective This study aimed to present the design and methods of Hprolipsis, an integrated viral hepatitis and HIV screening program administered to adults (≥18 years) from the general, Greek Roma, and migrant populations. Its aims were to estimate the prevalence of HBV, HCV, and HIV; assess infectious disease knowledge level; design, implement, and assess population-specific awareness actions; and offer individual counseling and referral when indicated and HBV vaccination to susceptible Roma and migrants. Methods Multistage, stratified, random sampling based on the 2011 Census was applied to select the general population sample, and nonprobability multistage quota sampling was used for Roma and migrant sample selection. Trained personnel made home (general population) or community (Roma and migrants) visits. Collected blood samples were tested for Hepatitis B surface Antigen, Hepatitis B core Antibody, Hepatitis B surface Antibody, Hepatitis C Antibody, and HIV 1,2 Antibody. The surveys were conducted during May 2013 and June 2016. To estimate an HCV prevalence of 1.5% with 0.3 precision, the required general population sample size was estimated to be 6000. As migrants constitute 10% of the whole Greek population, the migrant sample size was set to 600. A feasible sample size of 500 Greek Roma was set. Results In total, 6006 individuals from the general population (response rate 72%), 534 Greek Roma, and 612 migrants were recruited. Blood test results are available for 4245 individuals from the general population, 523 Roma, and 537 migrants. Conclusions Hprolipsis is the first nationwide survey on HBV, HCV, and HIV. Its results will enhance our understanding of the health needs and disease burden of these diseases in the 3 studied populations. Its implementation provided useful recommendations for future studies, particularly in vulnerable populations. International Registered Report Identifier (IRRID) DERR1-10.2196/13578

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Mdluli, Thembi, Ningbo Jian, Bonnie Slike, Dominic Paquin-Proulx, Gina Donofrio, Aljawharah Alrubayyi, Syna Gift, et al. "RV144 HIV-1 vaccination impacts post-infection antibody responses." PLOS Pathogens 16, no. 12 (December 8, 2020): e1009101. http://dx.doi.org/10.1371/journal.ppat.1009101.

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The RV144 vaccine efficacy clinical trial showed a reduction in HIV-1 infections by 31%. Vaccine efficacy was associated with stronger binding antibody responses to the HIV Envelope (Env) V1V2 region, with decreased efficacy as responses wane. High levels of Ab-dependent cellular cytotoxicity (ADCC) together with low plasma levels of Env-specific IgA also correlated with decreased infection risk. We investigated whether B cell priming from RV144 vaccination impacted functional antibody responses to HIV-1 following infection. Antibody responses were assessed in 37 vaccine and 63 placebo recipients at 6, 12, and 36 months following HIV diagnosis. The magnitude, specificity, dynamics, subclass recognition and distribution of the binding antibody response following infection were different in RV144 vaccine recipients compared to placebo recipients. Vaccine recipients demonstrated increased IgG1 binding specifically to V1V2, as well as increased IgG2 and IgG4 but decreased IgG3 to HIV-1 Env. No difference in IgA binding to HIV-1 Env was detected between the vaccine and placebo recipients following infection. RV144 vaccination limited the development of broadly neutralizing antibodies post-infection, but enhanced Fc-mediated effector functions indicating B cell priming by RV144 vaccination impacted downstream antibody function. However, these functional responses were not associated with clinical markers of disease progression. These data reveal that RV144 vaccination primed B cells towards specific binding and functional antibody responses following HIV-1 infection.

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Bhalara, Rohit Vasantbhai, Payal Shah, Ravi Kiritkumar Kothari, and Gauravi Dhruva. "Screening of Donated Blood for Transfusion Transmitted Infections by Serology and Response Rate to Notification of Reactive Results: A Tertiary Care Institutional Experience." Annals of Pathology and Laboratory Medicine 8, no. 2 (February 28, 2021): A63–68. http://dx.doi.org/10.21276/apalm.2969.

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Background: Safety for blood Transfusion begins with healthy donors. A basic part of preventing transfusion transmitted infections (TTIs) is to notify and counsel reactive donors. This study analysed trends in the prevalence of transfusion-transmissible infectious pathogens among blood donors and notify them as well as to assess response rate among them. Donor notification and counselling protect the health of the donor and stop secondary transmission of infectious diseases. Methods: 38707 blood donations were screened for TTIs, namely, HIV, HBV, HCV, and syphilis, Malarial Parasite by serology. ELISA testing for anti-HIV antibody, anti-HCV antibody and HBsAg and RPR test for syphilis, Rapid card test for Malarial Parasite. All reactive donors were retested in duplicate and notified of their status by communicating through telephone. Result: We evaluated 341 (0.88%) cases with reactive screening test results (0.617% HBV, 0.016% HCV, 0.134% HIV, 0.08% syphilis, 0.031% Malaria ). Only 179 donors (52.5%) responded to notification. The response among voluntary donors was better as compared to the replacement donors (54.1 % versus 40.7 %). Only 101 (57.22%) responsive donors followed their first attendance at referral clinic. Conclusion: Our study provides prevalence rate of TTIs among blood donors and importance of proper donor counselling and notification of TTI status to all reactive donors who opt to receive this information.

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Chen, Lin-Chi, David L. Goldman, Tamara L. Doering, Liise-anne Pirofski, and Arturo Casadevall. "Antibody Response to Cryptococcus neoformans Proteins in Rodents and Humans." Infection and Immunity 67, no. 5 (May 1, 1999): 2218–24. http://dx.doi.org/10.1128/iai.67.5.2218-2224.1999.

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ABSTRACT The prevalence and specificity of serum antibodies toCryptococcus neoformans proteins was studied in mice and rats with experimental infection, in individuals with or without a history of potential laboratory exposure to C. neoformans, human immunodeficiency virus (HIV)-positive individuals who developed cryptococcosis, in matched samples from HIV-positive individuals who did not develop cryptococcosis, and in HIV-negative individuals. Rodents had little or no serum antibody reactive with C. neoformans proteins prior to infection. The intensity and specificity of the rodent antibody response were dependent on the species, the mouse strain, and the viability of the inoculum. All humans had serum antibodies reactive with C. neoformans proteins regardless of the potential exposure, the HIV infection status, or the subsequent development of cryptococcosis. Our results indicate (i) a high prevalence of antibodies reactive with C. neoformansproteins in the sera of rodents after cryptococcal infection and in humans with or without HIV infection; (ii) qualitative and quantitative differences in the antibody profiles of HIV-positive individuals; and (iii) similarities and differences between humans, mice, and rats with respect to the specificity of the antibodies reactive with C. neoformans proteins. The results are consistent with the view that C. neoformans infections are common in human populations, and the results have implications for the development of vaccination strategies against cryptococcosis.

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Schroeder, Kristin M. S., Amanda Agazio, Pamela J. Strauch, Sean T. Jones, Scott B. Thompson, Michael S. Harper, Roberta Pelanda, Mario L. Santiago, and Raul M. Torres. "Breaching peripheral tolerance promotes the production of HIV-1–neutralizing antibodies." Journal of Experimental Medicine 214, no. 8 (July 11, 2017): 2283–302. http://dx.doi.org/10.1084/jem.20161190.

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A subset of characterized HIV-1 broadly neutralizing antibodies (bnAbs) are polyreactive with additional specificities for self-antigens and it has been proposed immunological tolerance may present a barrier to their participation in protective humoral immunity. We address this hypothesis by immunizing autoimmune-prone mice with HIV-1 Envelope (Env) and characterizing the primary antibody response for HIV-1 neutralization. We find autoimmune mice generate neutralizing antibody responses to tier 2 HIV-1 strains with alum treatment alone in the absence of Env. Importantly, experimentally breaching immunological tolerance in wild-type mice also leads to the production of tier 2 HIV-1–neutralizing antibodies, which increase in breadth and potency following Env immunization. In both genetically prone and experimentally induced mouse models of autoimmunity, increased serum levels of IgM anti-histone H2A autoantibodies significantly correlated with tier 2 HIV-1 neutralization, and anti-H2A antibody clones were found to neutralize HIV-1. These data demonstrate that breaching peripheral tolerance permits a cross-reactive HIV-1 autoantibody response able to neutralize HIV-1.

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Mascola, John R., Anna Sambor, Kristin Beaudry, Sampa Santra, Brent Welcher, Mark K. Louder, Thomas C. VanCott, et al. "Neutralizing Antibodies Elicited by Immunization of Monkeys with DNA Plasmids and Recombinant Adenoviral Vectors Expressing Human Immunodeficiency Virus Type 1 Proteins." Journal of Virology 79, no. 2 (January 15, 2005): 771–79. http://dx.doi.org/10.1128/jvi.79.2.771-779.2005.

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ABSTRACT Immunization with recombinant serotype 5 adenoviral (rAd5) vectors or a combination of DNA plasmid priming and rAd5 boosting is known to elicit potent immune responses. However, little data exist regarding these immunization strategies and the development of anti-human immunodeficiency virus type 1 (HIV-1) neutralizing antibodies. We used DNA plasmids and rAd5 vectors encoding the HIV-1 89.6P or chimeric HxB2/BaL envelope glycoprotein to immunize macaque monkeys. A single rAd5 immunization elicited anti-Env antibody responses, but there was little boosting with subsequent rAd5 immunizations. In contrast, rAd5 boosting of DNA-primed monkeys resulted in a rapid rise in antibody titers, including the development of anti-HIV-1 neutralizing antibodies. The potency and breadth of neutralization were evaluated by testing plasma against a panel of 14 clade B primary isolates. Moderate levels of plasma neutralizing activity were detected against about one-third of the viruses tested, and immunoglobulin G fractionation demonstrated that virus neutralization was antibody mediated. After a challenge with a chimeric simian-human immunodeficiency virus (SHIV89.6P), an anamnestic neutralizing antibody response was observed, although the breadth of the response was limited to the subset of viruses that were neutralized after the primary immunization. These data are the first detailed description of the anti-HIV-1 neutralizing antibody response in nonhuman primates elicited by DNA and rAd5 immunization. In addition to the well-established ability of DNA priming and rAd5 boosting to elicit potent anti-HIV-1 cellular immune responses, this immunization strategy elicits anti-HIV-1 neutralizing antibodies and therefore can be used to study novel Env immunogens designed to elicit more potent neutralizing antibodies.

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Forthal, Donald N., Gary Landucci, and Eric S. Daar. "Antibody from Patients with Acute Human Immunodeficiency Virus (HIV) Infection Inhibits Primary Strains of HIV Type 1 in the Presence of Natural-Killer Effector Cells." Journal of Virology 75, no. 15 (August 1, 2001): 6953–61. http://dx.doi.org/10.1128/jvi.75.15.6953-6961.2001.

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ABSTRACT The partial control of viremia during acute human immunodeficiency virus type 1 (HIV-1) infection is accompanied by an HIV-1-specific cytotoxic T-lymphocyte (CTL) response and an absent or infrequent neutralizing antibody response. The control of HIV-1 viremia has thus been attributed primarily, if not exclusively, to CTL activity. In this study, the role of antibody in controlling viremia was investigated by measuring the ability of plasma or immunoglobulin G from acutely infected patients to inhibit primary strains of HIV-1 in the presence of natural-killer (NK) effector cells. Antibody that inhibits virus when combined with effector cells was present in the majority of patients within days or weeks after onset of symptoms of acute infection. Furthermore, the magnitude of this effector cell-mediated antiviral antibody response was inversely associated with plasma viremia level, and both autologous and heterologous HIV-1 strains were inhibited. Finally, antibody from acutely infected patients likely reduced HIV-1 yield in vitro both by mediating effector cell lysis of target cells expressing HIV-1 glycoproteins and by augmenting the release of β-chemokines from NK cells. HIV-1-specific antibody may be an important contributor to the early control of HIV viremia.

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Burbelo, Peter D., Joseph A. Kovacs, Jason Wagner, Ahmad Bayat, Craig S. Rhodes, Yvonne De Souza, John S. Greenspan, and Michael J. Iadarola. "The Cancer-Associated Virus Landscape in HIV Patients with Oral Hairy Leukoplakia, Kaposi's Sarcoma, and Non-Hodgkin Lymphoma." AIDS Research and Treatment 2012 (2012): 1–10. http://dx.doi.org/10.1155/2012/634523.

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Although HIV-positive patients are at higher risk for developing a variety of infection-related cancers, the prevalence of infections with the seven known cancer-associated viruses has not been studied. Luciferase immunoprecipitation systems were used to evaluate antiviral antibodies in four 23-person groups: healthy blood donors and HIV-infected patients with oral hairy leukoplakia (OLP), Kaposi's sarcoma (KS), or non-Hodgkin lymphoma (NHL). Antibody profiling revealed that all HIV-positive individuals were strongly seropositive for anti-gp41 and antireverse transcriptase antibodies. However, anti-p24 HIV antibody levels were highly variable and some OLP and KS patients demonstrated weak or negative responses. Profiling two EBV antigens revealed no statistical difference in antibody levels among the three HIV-infected groups. A high frequency of KSHV infection was detected in HIV patients including 100% of KS, 78% of OLP, and 57% of NHL patients. Most HIV-infected subjects (84%) showed anti-HBV core antibodies, but only a few showed antibodies against HCV. MCV seropositivity was also common (94%) in the HIV-infected individuals and KS patients showed statistically higher antibody levels compared to the OLP and NHL patients. Overall, 68% of the HIV-infected patients showed seropositivity with at least four cancer-associated viruses. Antibody profiles against these and other infectious agents could be useful for enhancing the clinical management of HIV patients.

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Buxton, Jane A., and Jin Hee Kim. "Hepatitis A and Hepatitis B Vaccination Responses in Persons with Chronic Hepatitis C Infections: A Review of the Evidence and Current Recommendations." Canadian Journal of Infectious Diseases and Medical Microbiology 19, no. 2 (2008): 197–202. http://dx.doi.org/10.1155/2008/410362.

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In persons with chronic hepatitis C virus (HCV) infections, superinfection by hepatitis A virus (HAV) or hepatitis B virus (HBV) can cause serious complications, including fulminating hepatitis or increased severity of hepatitis. Therefore, it is important to adequately protect persons with chronic HCV infections by immunization. Suboptimal response to vaccines has been reported in patients with chronic liver disease. The present article reviews HAV and HBV vaccine responses reported in the literature when administered to individuals with chronic HCV infection, and reviews current national and international recommendations.RESULTS: Persons with chronic HCV respond well to HAV vaccine, but studies exploring HBV vaccine efficacy in this population have equivocal results. Vaccine schedules and participant characteristics differ among studies, and most do not adjust for confounders. Some studies found no difference in HBV vaccine response between patients with chronic HCV and controls. However, HBV vaccine response was generally reduced in those with cirrhosis and HCV genotype 1. Organizations recommend HAV and HBV vaccines for persons with chronic HCV, but do not suggest alterations in schedule or dose.RECOMMENDATIONS: Because HAV vaccine response is good and routine laboratory testing may not detect lower levels of vaccine-induced anti-HAV, the standard HAV vaccine schedule is recommended without postimmunization testing. HBV vaccine should be administered early in the course of chronic HCV infection because response may be lower in patients with cirrhosis. Reflex testing of anti-HCV reactive sera for anti-HAV and hepatitis B surface antibody can facilitate appropriate follow-up and timely immunization. Determination of postimmunization hepatitis B surface antibody, especially in patients with cirrhosis or genotype 1, will allow HBV vaccine boosters to be offered.

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Moore, Penny L. "The Neutralizing Antibody Response to the HIV-1 Env Protein." Current HIV Research 16, no. 1 (April 19, 2018): 21–28. http://dx.doi.org/10.2174/1570162x15666171124122044.

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Background: A vaccine able to elicit broadly neutralizing antibodies capable of blocking infection by global viruses has not been achieved, and remains a key public health challenge.Objective: During infection, a robust strain-specific neutralizing response develops in most people, but only a subset of infected people develop broadly neutralizing antibodies. Understanding how and why these broadly neutralizing antibodies develop has been a focus of the HIV-1 vaccine field for many years, and has generated extraordinary insights into the neutralizing response to HIV-1 infection.Results: This review describes the features, targets and developmental pathways of early strainspecific antibodies and later broadly neutralizing antibodies, and explores the reasons such broad antibodies are not more commonly elicited during infection.Conclusion: The insights from these studies have been harnessed for the development of pioneering new vaccine approaches that seek to drive B cell maturation towards breadth. Overall, this review describes how findings from infected donors have impacted on active and passive immunization approaches that seek to prevent HIV-1 infection.

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Thomson, Emma C., Eleni Nastouli, Janice Main, Peter Karayiannis, Joseph Eliahoo, David Muir, and Myra O. McClure. "Delayed anti-HCV antibody response in HIV-positive men acutely infected with HCV." AIDS 23, no. 1 (January 2009): 89–93. http://dx.doi.org/10.1097/qad.0b013e32831940a3.

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Heß, Rebecca, Michael Storcksdieck genannt Bonsmann, Dennis Lapuente, Andre Maaske, Carsten Kirschning, Jürgen Ruland, Bernd Lepenies, Drew Hannaman, Matthias Tenbusch, and Klaus Überla. "Glycosylation of HIV Env Impacts IgG Subtype Responses to Vaccination." Viruses 11, no. 2 (February 13, 2019): 153. http://dx.doi.org/10.3390/v11020153.

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The envelope protein (Env) is the only surface protein of the human immunodeficiency virus (HIV) and as such the exclusive target for protective antibody responses. Experimental evidences from mouse models suggest a modulating property of Env to steer antibody class switching towards the less effective antibody subclass IgG1 accompanied with strong TH2 helper responses. By simple physical linkage we were able to imprint this bias, exemplified by a low IgG2a/IgG1 ratio of antigen-specific antibodies, onto an unrelated antigen, namely the HIV capsid protein p24. Here, our results indicate the glycan moiety of Env as the responsible immune modulating activity. Firstly, in Card9−/− mice lacking specific C-Type lectin responsiveness, DNA immunization significantly increased the IgG2a/IgG1 ratio for the Env-specific antibodies while the antibody response against the F-protein of the respiratory syncytial virus (RSV) serving as control antigen remained unchanged. Secondly, sequential shortening of the Env encoding sequence revealed the C2V3 domain as responsible for the strong IgG1 responses and TH2 cytokine production. Removing all potential N-glycosylation sites from the C2V3 domain by site-specific mutagenesis reversed the vaccine-induced immune response towards a Th1-dominated T-cell response and a balanced IgG2a/IgG1 ratio. Accordingly, the stretch of oligomannose glycans in the C2V3 domain of Env might mediate a specific uptake and/or signaling modus in antigen presenting cells by involving interaction with an as yet unknown C-type lectin receptor. Our results contribute to a deeper understanding of the impact of Env glycosylation on HIV antigen-specific immune responses, which will further support HIV vaccine development.

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Redd, Andrew D., Nicole A. Doria-Rose, Joshua A. Weiner, Martha Nason, Matthew Seivers, Stephen D. Schmidt, Oliver Laeyendecker, et al. "Longitudinal Antibody Responses in People Who Inject Drugs Infected With Similar Human Immunodeficiency Virus Strains." Journal of Infectious Diseases 221, no. 5 (October 4, 2019): 756–65. http://dx.doi.org/10.1093/infdis/jiz503.

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Abstract Background Multiple factors influence the human immunodeficiency virus (HIV) antibody response produced during natural infection, leading to responses that can vary in specificity, strength, and breadth. Methods People who inject drugs identified as recently infected with HIV (n = 23) were analyzed for clustering of their viral sequences (genetic distance, <2%). Longitudinal antibody responses were identified for neutralizing antibody (Nab) potential, and differences in antibody subclass, specificity, and Fc receptor ligation using pseudovirus entry and multiplexed Fc array assays, respectively. Responses were analyzed for differences between subject groups, defined by similarity in the sequence of the infecting virus. Results Viral sequences from infected individuals were grouped into 3 distinct clusters with 7 unclustered individuals. Subjects in cluster 1 generally had lower antibody response magnitudes, except for antibodies targeting the V1/V2 region. Subjects in clusters 2 and 3 typically had higher antibody response magnitudes, with the Fv specificity of cluster 2 favoring gp140 recognition. NAb responses differed significantly between clusters for 3 of 18 pseudoviruses examined (P < .05), but there were no differences in overall NAb breadth (P = .62). Discussion These data demonstrate that individuals infected with similar viral strains can generate partially similar antibody responses, but these do not drastically differ from those in individuals infected with relatively unrelated strains.

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Papadopoulos, N. M., R. Costello, M. Ceroni, and H. M. Moutsopoulos. "Identification of HIV-specific oligoclonal immunoglobulins in serum of carriers of HIV antibody." Clinical Chemistry 34, no. 5 (May 1, 1988): 973–75. http://dx.doi.org/10.1093/clinchem/34.5.973.

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Abstract Zone electrophoresis on agarose gel was performed on serum samples from HIV-antibody carriers and negative controls. Nitrocellulose strips precoated with an HIV preparation were then placed on top of the gels and developed by an immunoblotting procedure. A positive reaction was demonstrated between the HIV antigens and the HIV-antibody-positive serum samples with hypergammaglobulinemia and oligoclonal IgG bands. A negative reaction was found between the HIV antigens and HIV-antibody-negative serum samples from a normal person and a patient with monoclonal gammopathy. The presence of oligoclonal IgG bands in the serum of HIV-antibody carriers, and their positive identification with HIV antigens, indicates a specific immune response of the host to the HIV infection and supports the use of oligoclonal IgG bands as markers to follow the course of HIV infection.

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Parren, Paul W. H. I., Paola Fisicaro, Carlos F. Barbas, Pascal Poignard, and Dennis R. Burton. "Characterization of the antibody response to HIV-1 envelope." Immunology Letters 56 (May 1997): 192. http://dx.doi.org/10.1016/s0165-2478(97)85770-7.

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Kliks, SrisakulC, and JayA Levy. "Maternal antibody response and maternal-infant HIV-1 transmission." Lancet 343, no. 8909 (May 1994): 1364. http://dx.doi.org/10.1016/s0140-6736(94)92501-1.

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Parren, P. "Characterization of the antibody response to HIV-1 envelope." Immunology Letters 56, no. 1-3 (May 1997): 192. http://dx.doi.org/10.1016/s0165-2478(97)87608-0.

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Juompan, Laure, Patrick Lambin, and Moncef Zouau. "Selective alterations of the antibody response to HIV-1." Applied Biochemistry and Biotechnology 75, no. 1 (October 1998): 139–50. http://dx.doi.org/10.1007/bf02787714.

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Ołdakowska, Agnieszka, Urszula Coupland, Sabina Dobosz, Jolanta Popielska, Małgorzata Szczepańska-Putz, and Magdalena Marczyńska. "Antibody response to VZV vaccination in HIV infected children." HIV & AIDS Review 14, no. 3 (2015): 76–79. http://dx.doi.org/10.1016/j.hivar.2015.03.004.

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Trinh, Gohain, Pham, Hamlin, Song, Sanders-Buell, Bose, et al. "Humoral Response to the HIV-1 Envelope V2 Region in a Thai Early Acute Infection Cohort." Cells 8, no. 4 (April 19, 2019): 365. http://dx.doi.org/10.3390/cells8040365.

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Reduced risk of HIV-1 infection correlated with antibody responses to the envelope variable 1 and 2 regions in the RV144 vaccine trial. To understand the relationship between antibody responses, V2 sequence, and structure, plasma samples (n = 16) from an early acute HIV-1 infection cohort from Thailand infected with CRF01_AE strain were analyzed for binding to V2 peptides by surface plasmon resonance. Five participants with a range of V2 binding responses at week 24 post-infection were further analyzed against a set of four overlapping V2 peptides that were designed based on envelope single-genome amplification. Antibody responses that were relatively consistent over the four segments of the V2 region or a focused response to the C-strand (residues 165–186) of the V2 region were observed. Viral escape in the V2 region resulted in significantly reduced antibody binding. Structural modeling indicated that the C-strand and the sites of viral variation were highly accessible in the open conformation of the HIV-1 Env trimer. V2 residues, 165–186 are preferentially targeted during acute infection. Residues 169–184 were also preferentially targeted by the protective immune response in the RV144 trial, thus emphasizing the importance of these residues for vaccine design.

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Kumar, Sanjeev, Himanshu Batra, Swarandeep Singh, Himanshi Chawla, Ravinder Singh, Sanket Katpara, Abdul Wahid Hussain, et al. "Effect of combination antiretroviral therapy on human immunodeficiency virus 1 specific antibody responses in subtype-C infected children." Journal of General Virology 101, no. 12 (December 1, 2020): 1289–99. http://dx.doi.org/10.1099/jgv.0.001480.

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Protective antibody responses to human immunodeficiency virus (HIV)-1 infection evolve only in a fraction of infected individuals by developing broadly neutralizing antibodies (bnAbs) and/or effector functions such as antibody-dependent cellular cytotoxicity (ADCC). HIV-1 chronically infected adults and children on combination antiretroviral therapy (cART) showed a reduction in ADCC activity and improvement in HIV-1 specific neutralizing antibody (nAb) responses. Early initiation of cART in infected adults is found to be beneficial in reducing the viral load and delaying disease progression. Herein, we longitudinally evaluated the effect of cART on HIV-1 specific plasma ADCC and nAb responses in a cohort of 20 perinatally HIV-1 subtype-C infected infants and children ≤2 years of age, pre-cART and up to 1 year post-cART initiation. Significant reductions in HIV-1 specific plasma ADCC responses to subtype-C and subtype-B viruses and improvement in HIV-1 neutralization were observed in HIV-1 infected children 1 year post-cART initiation. A positive correlation between reduction in viral load and the loss of ADCC response was observed. This study provides information aiding the understanding of the effects of early initiation of cART on antibody effector functions and viral neutralization in HIV-1 infected children, which needs to be further evaluated in large cohorts of HIV-1 infected children on cART to plan future intervention strategies.

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Delfraissy, Jean-François, Christine Wallon, François Boué, Cécile Goujard, Françoise Barré-Sinoussi, and Pierre Galanaud. "HIV-induced, HIV-specific in vitro antibody response by B-cells from HIV-seropositive individuals." AIDS 6, no. 1 (January 1992): 55–64. http://dx.doi.org/10.1097/00002030-199201000-00007.

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Zhang, Peng Fei, Xi Chen, Da Wei Fu, Joseph B. Margolick, and Gerald V. Quinnan. "Primary Virus Envelope Cross-Reactivity of the Broadening Neutralizing Antibody Response during Early Chronic Human Immunodeficiency Virus Type 1 Infection." Journal of Virology 73, no. 6 (June 1, 1999): 5225–30. http://dx.doi.org/10.1128/jvi.73.6.5225-5230.1999.

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ABSTRACT To test the hypothesis that changing neutralizing antibody responses against human immunodeficiency virus type 1 (HIV-1) during chronic infection were a response to emergence of neutralization escape mutants, we cloned expressed and characterized envelope clones from patients in the Multicenter AIDS Cohort Study (MACS). Pseudotyped HIV-1 envelope clones obtained from differing time points were assessed for sensitivity to neutralization by using sera from different times from the same and different patients. Clones from early and late time points during chronic infection had similar neutralization sensitivity, and neutralizing antibody responses cross-reacted with early, late, and heterologous envelopes. The potential for broadly effective HIV-1 immunization is supported.

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Deeks, Steven G., Becky Schweighardt, Terri Wrin, Justin Galovich, Rebecca Hoh, Elizabeth Sinclair, Peter Hunt, et al. "Neutralizing Antibody Responses against Autologous and Heterologous Viruses in Acute versus Chronic Human Immunodeficiency Virus (HIV) Infection: Evidence for a Constraint on the Ability of HIV To Completely Evade Neutralizing Antibody Responses." Journal of Virology 80, no. 12 (June 15, 2006): 6155–64. http://dx.doi.org/10.1128/jvi.00093-06.

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ABSTRACT Acute human immunodeficiency virus (HIV) infection is associated with the rapid development of neutralization escape mutations. The degree to which viral evolution persists in chronic infection has not been well characterized, nor is it clear if all patients develop high-level neutralization antibody escape. We therefore measured neutralizing antibody responses against autologous and heterologous viruses in a cohort of acutely and chronically infected subjects (n = 65). Neutralizing antibody responses against both autologous virus and heterologous viruses were lower among individuals with acute infection than among those with chronic infection. Among chronically infected individuals, there was a negative correlation between the level of neutralizing antibodies against autologous virus and the level of viremia. In contrast, there was a positive correlation between the level of neutralizing antibodies against a panel of heterologous viruses and the level of viremia. Viral evolution, as defined by the presence of higher neutralizing titers directed against earlier viruses than against contemporaneous viruses, was evident for subjects with recent infection but absent for those with chronic infection. In summary, neutralizing antibody responses against contemporaneous autologous viruses are absent in early HIV infection but can be detected at low levels in chronic infection, particularly among those controlling HIV in the absence of therapy. HIV replication either directly or indirectly drives the production of increasing levels of antibodies that cross-neutralize heterologous primary isolates. Collectively, these observations indicate that although HIV continuously drives the production of neutralizing antibodies, there may be limits to the capacity of the virus to evolve continuously in response to these antibodies. These observations also suggest that the neutralizing antibody response may contribute to the long-term control of HIV in some patients while protecting against HIV superinfection in most patients.

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Forsell, Mattias N. E., Yuxing Li, Maria Sundbäck, Krisha Svehla, Peter Liljeström, John R. Mascola, Richard Wyatt, and Gunilla B. Karlsson Hedestam. "Biochemical and Immunogenic Characterization of Soluble Human Immunodeficiency Virus Type 1 Envelope Glycoprotein Trimers Expressed by Semliki Forest Virus." Journal of Virology 79, no. 17 (September 1, 2005): 10902–14. http://dx.doi.org/10.1128/jvi.79.17.10902-10914.2005.

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ABSTRACT The current lack of envelope glycoprotein immunogens that elicit broadly neutralizing antibody responses remains a major challenge for human immunodeficiency virus type 1 (HIV-1) vaccine development. However, the recent design and construction of stable soluble gp140 trimers have shown that some neutralization breadth can be achieved by using immunogens that better mimic the functional viral spike complex. The use of genetic delivery systems to drive the in vivo expression of such immunogens for the stimulation of neutralizing antibodies against HIV-1 may offer advantages by maintaining the quaternary structure of the trimeric envelope glycoproteins. Here, we describe the biochemical and immunogenic properties of soluble HIV-1 envelope glycoprotein trimers expressed by recombinant Semliki Forest virus (rSFV). The results presented here demonstrate that rSFV supports the expression of stable soluble gp140 trimers that retain recognition by conformationally sensitive antibodies. Further, we show that rSFV particle immunizations efficiently primed immune responses as measured after a single boost with purified trimeric gp140 protein, resulting in a Th1-biased antibody response. This differed from the Th2-biased antibody response obtained after repeated immunizations with purified gp140 protein trimers. Despite this difference, both regimens stimulated neutralizing antibody responses of similar potency. This suggests that rSFV may be a useful component of a viral vector prime-protein boost regimen aimed at stimulating both cell-mediated immune responses and neutralizing antibodies against HIV-1.

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Joachim, Agricola, Frank Msafiri, Sayali Onkar, Patricia Munseri, Said Aboud, Eligius F. Lyamuya, Muhammad Bakari, et al. "Frequent and Durable Anti-HIV Envelope VIV2 IgG Responses Induced by HIV-1 DNA Priming and HIV-MVA Boosting in Healthy Tanzanian Volunteers." Vaccines 8, no. 4 (November 13, 2020): 681. http://dx.doi.org/10.3390/vaccines8040681.

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We evaluated antibody responses to the human immunodeficiency virus (HIV) envelope variable regions 1 and 2 (V1V2) in 29 vaccinees who had received three HIV-1 DNA immunizations and two HIV-modified vaccinia virus Ankara (MVA) boosts in the phase I/II HIVIS03 vaccine trial. Twenty vaccinees received a third HIV-MVA boost after three years in the HIVIS06 trial. IgG and IgG antibody subclasses to gp70V1V2 proteins of HIV-1 A244, CN54, Consensus C, and Case A2 were analysed using an enzyme-linked immunosorbent assay (ELISA). Cyclic V2 peptides of A244, Consensus C, and MN were used in a surface plasmon resonance (SPR) assay. Four weeks after the second HIV-MVA, anti-V1V2 IgG antibodies to A244 were detected in 97% of HIVIS03 vaccinees, in 75% three years later, and in 95% after the third HIV-MVA. Anti-CN54 V1V2 IgG was detectable in 48% four weeks after the second HIV-MVA. The SPR data supported the findings. The IgG response was predominantly IgG1. Four weeks after the second HIV-MVA, 85% of vaccinees had IgG1 antibodies to V1V2 A244, which persisted in 25% for three-years. IgG3 and IgG4 antibodies to V1V2 A244 were rare. In conclusion, the HIV-DNA/MVA vaccine regimen induced durable V1V2 IgG antibody responses in a high proportion of vaccinees.

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Lewis, Anne D., Ruju Chen, David C. Montefiori, Philip R. Johnson, and K. Reed Clark. "Generation of Neutralizing Activity against Human Immunodeficiency Virus Type 1 in Serum by Antibody Gene Transfer." Journal of Virology 76, no. 17 (September 1, 2002): 8769–75. http://dx.doi.org/10.1128/jvi.76.17.8769-8775.2002.

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ABSTRACT Although several human immunodeficiency virus (HIV) vaccine approaches have elicited meaningful antigen-specific T-cell responses in animal models, no single vaccine candidate has engendered antibodies that broadly neutralize primary isolates of HIV type 1 (HIV-1). Thus, there remains a significant gap in the design of HIV vaccines. To address this issue, we exploited the existence of rare human monoclonal antibodies that have been isolated from HIV-infected individuals. Such antibodies neutralize a wide array of HIV-1 field isolates and have been shown to be effective in vivo. However, practical considerations preclude the use of antibody preparations as a prophylactic passive immunization strategy in large populations. Our concept calls for an antibody gene of choice to be transferred to muscle where the antibody molecule is synthesized and distributed to the circulatory system. In these experiments, we used a recombinant adeno-associated virus (rAAV) vector to deliver the gene for the human antibody IgG1b12 to mouse muscle. Significant levels of HIV-neutralizing activity were found in the sera of mice for over 6 months after a single intramuscular administration of the rAAV vector. This approach allows for predetermination of antibody affinity and specificity prior to “immunization” and avoids the need for an active humoral immune response against the HIV envelope protein.

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Chaillon, Antoine, Gabriel A. Wagner, N. Lance Hepler, Susan J. Little, Sergei L. Kosakovsky Pond, Gemma Caballero, Mary E. Pacold, et al. "Dynamics of Viral Evolution and Neutralizing Antibody Response after HIV-1 Superinfection." Journal of Virology 87, no. 23 (September 18, 2013): 12737–44. http://dx.doi.org/10.1128/jvi.02260-13.

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Investigating the incidence and prevalence of HIV-1 superinfection is challenging due to the complex dynamics of two infecting strains. The superinfecting strain can replace the initial strain, be transiently expressed, or persist along with the initial strain in distinct or in recombined forms. Various selective pressures influence these alternative scenarios in different HIV-1 coding regions. We hypothesized that the potency of the neutralizing antibody (NAb) response to autologous viruses would modulate viral dynamics inenvfollowing superinfection in a limited set of superinfection cases. HIV-1envpyrosequencing data were generated from blood plasma collected from 7 individuals with evidence of superinfection. Viral variants within each patient were screened for recombination, and viral dynamics were evaluated using nucleotide diversity. NAb responses to autologous viruses were evaluated before and after superinfection. In 4 individuals, the superinfecting strain replaced the original strain. In 2 individuals, both initial and superinfecting strains continued to cocirculate. In the final individual, the surviving lineage was the product of interstrain recombination. NAb responses to autologous viruses that were detected within the first 2 years of HIV-1 infection were weak or absent for 6 of the 7 recently infected individuals at the time of and shortly following superinfection. These 6 individuals had detectable on-going viral replication of distinct superinfecting virus in theenvcoding region. In the remaining case, there was an early and strong autologous NAb response, which was associated with extensive recombination inenvbetween initial and superinfecting strains. This extensive recombination made superinfection more difficult to identify and may explain why the detection of superinfection has typically been associated with low autologous NAb titers.

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De La Rosa, Indhira, Iona M. Munjal, Maria Rodriguez-Barradas, Xiaoying Yu, Liise-anne Pirofski, and Daniel Mendoza. "Protease Inhibitors Do Not Affect Antibody Responses to Pneumococcal Vaccination." Clinical and Vaccine Immunology 23, no. 6 (April 13, 2016): 524–29. http://dx.doi.org/10.1128/cvi.00026-16.

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ABSTRACTHIV+subjects on optimal antiretroviral therapy have persistently impaired antibody responses to pneumococcal vaccination. We explored the possibility that this effect may be due to HIV protease inhibitors (PIs). We found that in humans and mice, PIs do not affect antibody production in response to pneumococcal vaccination.

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Gonçalves, Paloma, Francisco Martin, Patricia Borges, Maria Espirito Santo, Nuno Taveira, and José Marcelino. "PO 8597 NEUTRALISING AND NON-NEUTRALISING ANTIBODIES RESPONSE IN HIV-1-INFECTED INDIVIDUALS FROM MOZAMBIQUE." BMJ Global Health 4, Suppl 3 (April 2019): A61.2—A61. http://dx.doi.org/10.1136/bmjgh-2019-edc.161.

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BackgroundA vaccine that protects against the different HIV subtypes circulating around the world is essential to control and eliminate HIV infection. The immunogens are the key to develop an effective HIV vaccine. In this study, we characterised the antibody response against recombinant C2V3C3 polypeptides from several HIV-1 subtypes and evaluated the neutralising antibody response.MethodsPlasmas from HIV-1-infected individuals under treatment (n=39) and drugs-naïve individuals (n=8) were tested in an ELISA assay to determine the presence of antibodies against polypeptides from HIV-1 subtypes (CRF02_AG, B, C, G and H). The neutralising activity of plasma was evaluated with a panel of six HIV-1 viruses from a reference panel, [one tier 1 (NL4.3), and five tier 2 (PCH119_CRF07, PCE1176_C, TRO11_B, 246 F3_AC and CRF07_BJOX2000)] in a TZM-bl cells-based assay.ResultsOut of 48 plasmas, 44 (89.6%) reacted at least with one polypeptide and four (10.4%) did not react with any polypeptide. Interestingly, 56% of the plasmas recognise ≥3 peptides and 6 reacted with all polypeptides. The polypeptide from virus CRF02_AG was the most antigenic (77%) followed by the polypeptide C (58.3%), G (58.3%), H (50%) and B (35.4%). There was a positive correlation between polypeptides number recognised and binding antibody reactivity (r=0.4895, p=0.0111). All plasmas from drugs-naïve individuals neutralised at least one virus with neutralising activity between 39.3% and 95.7%. Four plasmas showed neutralising activity >50% against five viruses. The virus 249 F3 was the easiest to neutralise (median, 65.7%), whereas PCH119_CRF07 was the most difficult to neutralise (median, 43.6%). Neutralising activity of plasmas from patients under treatment are ongoing.ConclusionIn summary, these polypeptides could be useful in vaccine design once they are very antigenic and we observed a heterologous neutralising antibody response in naïve patients that expressed positive antibody-response anti-peptides.

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Moore, Penny L., Emma T. Crooks, Lauren Porter, Ping Zhu, Charmagne S. Cayanan, Henry Grise, Paul Corcoran, et al. "Nature of Nonfunctional Envelope Proteins on the Surface of Human Immunodeficiency Virus Type 1." Journal of Virology 80, no. 5 (March 1, 2006): 2515–28. http://dx.doi.org/10.1128/jvi.80.5.2515-2528.2006.

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ABSTRACT Human immunodeficiency virus type 1 (HIV-1) neutralizing antibodies are thought be distinguished from nonneutralizing antibodies by their ability to recognize functional gp120/gp41 envelope glycoprotein (Env) trimers. The antibody responses induced by natural HIV-1 infection or by vaccine candidates tested to date consist largely of nonneutralizing antibodies. One might have expected a more vigorous neutralizing response, particularly against virus particles that bear functional trimers. The recent surprising observation that nonneutralizing antibodies can specifically capture HIV-1 may provide a clue relating to this paradox. Specifically, it was suggested that forms of Env, to which nonneutralizing antibodies can bind, exist on virus surfaces. Here, we present evidence that HIV-1 particles bear nonfunctional gp120/gp41 monomers and gp120-depleted gp41 stumps. Using a native electrophoresis band shift assay, we show that antibody-trimer binding predicts neutralization and that the nonfunctional forms of Env may account for virus capture by nonneutralizing antibodies. We hypothesize that these nonfunctional forms of Env on particle surfaces serve to divert the antibody response, helping the virus to evade neutralization.

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Fouts, Timothy R., Kenneth Bagley, Ilia J. Prado, Kathryn L. Bobb, Jennifer A. Schwartz, Rong Xu, Robert J. Zagursky, et al. "Balance of cellular and humoral immunity determines the level of protection by HIV vaccines in rhesus macaque models of HIV infection." Proceedings of the National Academy of Sciences 112, no. 9 (February 13, 2015): E992—E999. http://dx.doi.org/10.1073/pnas.1423669112.

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A guiding principle for HIV vaccine design has been that cellular and humoral immunity work together to provide the strongest degree of efficacy. However, three efficacy trials of Ad5-vectored HIV vaccines showed no protection. Transmission was increased in two of the trials, suggesting that this vaccine strategy elicited CD4+ T-cell responses that provide more targets for infection, attenuating protection or increasing transmission. The degree to which this problem extends to other HIV vaccine candidates is not known. Here, we show that a gp120-CD4 chimeric subunit protein vaccine (full-length single chain) elicits heterologous protection against simian-human immunodeficiency virus (SHIV) or simian immunodeficiency virus (SIV) acquisition in three independent rhesus macaque repeated low-dose rectal challenge studies with SHIV162P3 or SIVmac251. Protection against acquisition was observed with multiple formulations and challenges. In each study, protection correlated with antibody-dependent cellular cytotoxicity specific for CD4-induced epitopes, provided that the concurrent antivaccine T-cell responses were minimal. Protection was lost in instances when T-cell responses were high or when the requisite antibody titers had declined. Our studies suggest that balance between a protective antibody response and antigen-specific T-cell activation is the critical element to vaccine-mediated protection against HIV. Achieving and sustaining such a balance, while enhancing antibody durability, is the major challenge for HIV vaccine development, regardless of the immunogen or vaccine formulation.

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van Schooten, Jelle, Marlies M. van Haaren, Hui Li, Laura E. McCoy, Colin Havenar-Daughton, Christopher A. Cottrell, Judith A. Burger, et al. "Antibody responses induced by SHIV infection are more focused than those induced by soluble native HIV-1 envelope trimers in non-human primates." PLOS Pathogens 17, no. 8 (August 25, 2021): e1009736. http://dx.doi.org/10.1371/journal.ppat.1009736.

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The development of an effective human immunodeficiency virus (HIV-1) vaccine is a high global health priority. Soluble native-like HIV-1 envelope glycoprotein trimers (Env), including those based on the SOSIP design, have shown promise as vaccine candidates by inducing neutralizing antibody responses against the autologous virus in animal models. However, to overcome HIV-1’s extreme diversity a vaccine needs to induce broadly neutralizing antibodies (bNAbs). Such bNAbs can protect non-human primates (NHPs) and humans from infection. The prototypic BG505 SOSIP.664 immunogen is based on the BG505 env sequence isolated from an HIV-1-infected infant from Kenya who developed a bNAb response. Studying bNAb development during natural HIV-1 infection can inform vaccine design, however, it is unclear to what extent vaccine-induced antibody responses to Env are comparable to those induced by natural infection. Here, we compared Env antibody responses in BG505 SOSIP-immunized NHPs with those in BG505 SHIV-infected NHPs, by analyzing monoclonal antibodies (mAbs). We observed three major differences between BG505 SOSIP immunization and BG505 SHIV infection. First, SHIV infection resulted in more clonal expansion and less antibody diversity compared to SOSIP immunization, likely because of higher and/or prolonged antigenic stimulation and increased antigen diversity during infection. Second, while we retrieved comparatively fewer neutralizing mAbs (NAbs) from SOSIP-immunized animals, these NAbs targeted more diverse epitopes compared to NAbs from SHIV-infected animals. However, none of the NAbs, either elicited by vaccination or infection, showed any breadth. Finally, SOSIP immunization elicited antibodies against the base of the trimer, while infection did not, consistent with the base being placed onto the virus membrane in the latter setting. Together these data provide new insights into the antibody response against BG505 Env during infection and immunization and limitations that need to be overcome to induce better responses after vaccination.

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Permar, Sallie R., Andrew B. Wilks, Elizabeth P. Ehlinger, Helen H. Kang, Tatenda Mahlokozera, Rory T. Coffey, Angela Carville, Norman L. Letvin, and Michael S. Seaman. "Limited Contribution of Mucosal IgA to Simian Immunodeficiency Virus (SIV)-Specific Neutralizing Antibody Response and Virus Envelope Evolution in Breast Milk of SIV-Infected, Lactating Rhesus Monkeys." Journal of Virology 84, no. 16 (June 2, 2010): 8209–18. http://dx.doi.org/10.1128/jvi.00656-10.

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ABSTRACT Breast milk transmission of human immunodeficiency virus (HIV) remains an important mode of infant HIV acquisition. Interestingly, the majority of infants remain uninfected during prolonged virus exposure via breastfeeding, raising the possibility that immune components in milk prevent mucosal virus transmission. HIV-specific antibody responses are detectable in the milk of HIV-infected women and simian immunodeficiency virus (SIV)-infected monkeys; however, the role of these humoral responses in virus neutralization and local virus quasispecies evolution has not been characterized. In this study, four lactating rhesus monkeys were inoculated with SIVmac251 and monitored for SIV envelope-specific humoral responses and virus evolution in milk and plasma throughout infection. While the kinetics and breadth of the SIV-specific IgG and IgA responses in milk were similar to those in plasma, the magnitude of the milk responses was considerably lower than that of the plasma responses. Furthermore, a neutralizing antibody response against the inoculation virus was not detected in milk samples at 1 year after infection, despite a measurable autologous neutralizing antibody response in plasma samples obtained from three of four monkeys. Interestingly, while IgA is the predominant immunoglobulin in milk, the milk SIV envelope-specific IgA response was lower in magnitude and demonstrated more limited neutralizing capacity against a T-cell line-adapted SIV compared to those of the milk IgG response. Finally, amino acid mutations in the envelope gene product of SIV variants in milk and plasma samples occurred in similar numbers and at similar positions, indicating that the humoral immune pressure in milk does not drive distinct virus evolution in the breast milk compartment.

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Aasa-Chapman, Marlén MI, Anna Hayman, Philippa Newton, David Cornforth, Ian Williams, Persephone Borrow, Peter Balfe, and Áine McKnight. "Development of the antibody response in acute HIV-1 infection." AIDS 18, no. 3 (February 2004): 371–81. http://dx.doi.org/10.1097/00002030-200402200-00002.

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VanBlargan, Laura A., Leslie Goo, and Theodore C. Pierson. "Deconstructing the Antiviral Neutralizing-Antibody Response: Implications for Vaccine Development and Immunity." Microbiology and Molecular Biology Reviews 80, no. 4 (October 26, 2016): 989–1010. http://dx.doi.org/10.1128/mmbr.00024-15.

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SUMMARYThe antibody response plays a key role in protection against viral infections. While antiviral antibodies may reduce the viral burden via several mechanisms, the ability to directly inhibit (neutralize) infection of cells has been extensively studied. Eliciting a neutralizing-antibody response is a goal of many vaccine development programs and commonly correlates with protection from disease. Considerable insights into the mechanisms of neutralization have been gained from studies of monoclonal antibodies, yet the individual contributions and dynamics of the repertoire of circulating antibody specificities elicited by infection and vaccination are poorly understood on the functional and molecular levels. Neutralizing antibodies with the most protective functionalities may be a rare component of a polyclonal, pathogen-specific antibody response, further complicating efforts to identify the elements of a protective immune response. This review discusses advances in deconstructing polyclonal antibody responses to flavivirus infection or vaccination. Our discussions draw comparisons to HIV-1, a virus with a distinct structure and replication cycle for which the antibody response has been extensively investigated. Progress toward deconstructing and understanding the components of polyclonal antibody responses identifies new targets and challenges for vaccination strategies.

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Alshaikh, M. A., N. H. AlShamrani, and A. M. Elaiw. "Stability of HIV/HTLV co-infection model with effective HIV-specific antibody immune response." Results in Physics 27 (August 2021): 104448. http://dx.doi.org/10.1016/j.rinp.2021.104448.

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Journal articles on the topic 'Antibody response to HIV'

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