Academic literature on the topic 'Rabies virus vectors'

The recombinant vaccinia–rabies vaccine, now known as Raboral®, has been widely used in Europe and North America to control/eliminate rabies in the principal wildlife vectors, and thus prevent human transmission. The origins of this vaccine are sometimes forgotten, although the formulation has not changed substantially in almost four decades. This groundbreaking vaccine was assembled by a team at a very young (at that time) genetic engineering company, Transgène, in Strasbourg, France. The joint leaders of the rabies vaccine team reflect, 36 years later, on the trials and tribulations that went hand in hand with the construction of the vaccine.

The Rhabdoviridae are a large family of RNA viruses, two genera of which infect animals: the genus Lyssavirus contains rabies and rabies-related viruses that cause at least 55,000 deaths annually in Asia and Africa. The risks and problems posed by rabies and other lyssaviruses vary across the world. Viruses can penetrate broken skin and intact mucosae. Humans are usually infected when virus-laden saliva is inoculated through the skin by the bite of a rabid animal, usually a dog. Although the greatest threat to man is the persistent cycle of infection in stray dogs, several other terrestrial mammal species are reservoirs of infection. In the Americas, bat viruses and also classic type 1 rabies and insectivorous bats have become the principal vectors of infection to humans in the United States of America. Elsewhere in the world, there is increasing evidence of widespread rabies-related lyssavirus infection of bats.

The term zoonosis comes from the Greek: ζῷον (zoon) ‘animal’ and νόσος (nosos) ‘sickness’, and means an infection transmissible from animals to humans. Infected animals can be symptomatic or asymptomatic, and humans usually become accidental hosts through close contact with the reservoir animal. Six out of ten infections in humans globally are spread from animals, and 75% of emerging infections are zoonotic. Some occur worldwide e.g. E. coli O157:H7, whereas some are more restricted geographically, e.g. Ebola virus. The highest burden is in developing countries. There are various classifications of zoonoses. ● Causative pathogen: bacterial (anthrax, non-typhoidal Salmonelloses); viral (rabies, Yellow Fever, hantaviruses); parasitic (hookworm, Giardia, toxoplasmosis); fungal (dermatophytes, histoplasmosis); or prion (new-variant Creutzfeldt-Jakob disease). ● Mode of transmission (see Section 35.3 and Table 35.1 below) ● Distribution: endemic zoonoses are continually present in a population (e.g. leptospirosis, brucellosis); epidemic zoonoses occur intermittently (e.g. anthrax, Rift Valley Fever); emerging zoonoses are new infections, or existing infections that are increasing in incidence or geographical range (e.g. Nipah virus, Middle East Respiratory Syndrome coronavirus). ● Direct contact: infectious particles are present on an infected animal, in its body fluids, and in its excreta. Q fever, caused by Coxiella burnetii, and brucellosis may be acquired by direct contact with infected animals, particularly during parturition; cat-scratch disease caused by Bartonella henselae, and Pasteurella spp. may be acquired by bites or scratches from cats, and rabies from canine bites. Many zoonoses are also transmitted via indirect animal contact through exposure to soil or water contaminated by infectious material, e.g. leptospirosis may be acquired when water contaminated with infected rats’ urine comes into contact with broken skin or mucous membranes. ● Ingestion: infection occurs by ingesting contaminated food or water, e.g. unpasteurized milk, poorly processed or undercooked meat, or by eating/ drinking after handling animals without handwashing. Listeria, bovine tuberculosis, and brucellosis may be transmitted by unpasteurized milk and dairy produce; Hepatitis E through processed pork, and Ebola and Marburg through bushmeat. ● Vector-borne: infection is transmitted through a biting arthropod vector. Examples include West Nile Virus and Japanese encephalitis from mosquitoes, Lyme disease, tick-borne encephalitis, and Rocky Mountain Spotted Fever from ticks, and Rickettsia typhi from rat fleas.

Vaccines can be classified according to their nature into the following types: ● Inactivated vaccines: ■ Whole organism; ■ Acellular extracts. ● Live attenuated vaccines. ● Toxoid vaccines. ● Subunit vaccines. ● Conjugate vaccines. ● DNA vaccines. ● Recombinant vector vaccines. Inactivation of the whole organism is the most basic form of vaccine produced by killing the micro-organism causing the disease using heat, chemical or radiation and presents all the antigens in the inactivated organism as a vaccine to induce immunity in the recipient. Other methods to produce an inactivated vaccine is by extracting acellular components of the organism through filtration. Examples of inactivated bacterial vaccines currently in use include: ● Anthrax—sterile filtrate from cultures of the Sterne strain of B. anthracis. ● Cholera—oral inactivated vaccine with 1mg of recombinant cholera toxin B (rCTB) in a liquid suspension of four strains of killed V. cholerae O1, representing subtypes Inaba and Ogawa and biotypes El Tor and classical. ● Pertussis—acellular vaccine has replaced previously used whole cell vaccine. ● Typhoid—purified Vi capsular polysaccharide from S. typhi; NB: the injectable, killed, whole-cell typhoid vaccine which contains heat-inactivated, phenol-preserved S. typhi organisms is no longer in use in the UK. Examples of inactivated viral vaccines currently in use in the UK include: ● Hepatitis A virus. ● Hepatitis E virus. ● Influenza A and B viruses. ● Japanese encephalitis virus. ● Polio viruses 1, 2, and 3 (IPV). ● Rabies virus. ● Tick-borne encephalitis virus. ● Bacterial vaccines: Bacillus Calmette-Guerin (BCG) vaccine is a live attenuated vaccine against tuberculosis derived from a Mycobacterium bovis strain. The oral typhoid vaccine contains a live attenuated strain of S. typhi (Ty21a) in an enteric-coated capsule. ● Viral vaccines: The measles, mumps, and rubella (MMR) vaccine contain live attenuated strains of measles, mumps, and rubella viruses, which are cultured separately and mixed before being lyophilized. Oral polio vaccine (OPV) against polio viruses 1, 2, and 3—OPV contains live attenuated strains of poliomyelitis virus types 1, 2, and 3 grown in cell cultures.