are harmless agents, perceived as enemies. They are molecules, usually but not necessarily proteins, that elicit an immune response, thereby providing protective immunity against a potential pathogen. While the pathogen can be a bacterium or even a eukaryotic protozoan, most successful vaccines have been raised against viruses and here we shall deal mostly with anti-viral vaccines.
Immunity to a virus normally depends on the development of an immune response to antigens on the surface of a virally infected cell or on the surface of the virus particle itself. Immune responses to internal antigens usually play little role in immunity. Thus, in influenza pandemics, a novel surface glycoprotein acquired as a result of antigenic shift characterizes the new virus strain against which the population has little or no immunity. This new strain of influenza virus may, nevertheless, contain internal proteins that have been in previous influenza strains. Surface glycoproteins are often referred to as protective antigens. To make a successful vaccine against a virus, the nature of these surface antigens must be known unless the empirical approach of yesteryear is to be followed. It should be noted, however, that a virally-infected cell displays fragments of internal virus antigens on its surface and these can elicit a cytotoxic T cell response that acts against the infected cell.
There may be more than one surface glycoprotein on a virus and one of these may be more important in the protective immune response than the others; this antigen must be identified for a logical vaccine that blocks infectivity. For example, influenza virus has a neuraminidase and a hemagglutinin on the surface of the virus particle. It is the hemagglutinin that provokes neutralizing immunity because it is the protein that attaches the virus to a cell surface receptor and the neutralizing antibody interferes with virus binding to the cell.
In addition to blocking cell to virus attachment, other factors can be important in the neutralization of viruses; for example, complement can lyse enveloped virions after opsonization by anti-viral antibodies.
Major sites of viral infection
In order to develop a successful vaccine, certain characteristics of the viral infection must be known. One of these is the site at which the virus enters the body. Three major sites may be defined:
1) Infection via mucosal surfaces of the respiratory tract and gastro-intestinal tract.
Virus families in this group are: rhinoviruses; myxoviruses; coronaviruses; parainfluenzaviruses; respiratory syncytial viruses; rotaviruses
2) Infection via mucosal surfaces followed by spread systemically via the blood and/or neurones to target organs.
Virus families in this group are: picornaviruses; measles virus; mumps virus; herpes simplex virus; varicella virus; hepatitis A and B viruses
3) Infection via needles or insect bites, followed by spread to target organs:
Virus families in this group are hepatitis B virus; alphaviruses; flaviviruses; bunyaviruses
IgA-mediated local immunity is very important in types 1 and 2. There is little point in having a good neutralizing humoral antibody in the circulation when the virus replicates, for example, in the upper respiratory tract. Clearly, here secreted antibodies are important.
Thus, we need to know:
Viral antigen(s) that elicit neutralizing antibody
Cell surface antigen(s) that elicit neutralizing antibody
The site of replication of the virus
Types of vaccines
There are three basic types of in use today
Killed vaccines: These are preparations of the normal (wild type) infectious, pathogenic virus that has been rendered non-pathogenic, usually by chemical treatment such as with formalin that cross-links viral proteins.
Attenuated vaccines: These are live virus particles that grow in the vaccine recipient but do not cause disease because the vaccine virus has been altered (mutated) to a non-pathogenic form; for example, its tropism has been altered so that it no longer grows at a site that can cause disease.
Sub-unit vaccines: These are purified components of the virus, such as a surface antigen.
Problems in vaccine development
There are many problems inherent in developing a good protective anti-viral vaccine. Among these are:
Different types of virus may cause similar diseases--e.g. common cold. As a result, a single vaccine will not be possible against such a disease
Antigenic drift and shift -- This is especially true of RNA viruses and those with segmented genomes
Large animal reservoirs. If these occur, reinfection after elimination from the human population may occur
Integration of viral DNA. Vaccines will not work on latent virions unless they express antigens on cell surface. In addition, if the vaccine virus integrates into host cell chromosomes, it may cause problems (This is, for example, a problem with the possible use of anti-HIV vaccines based on attenuated virus strains- see later)
Transmission from cell to cell via syncytia - This is a problem for potential AIDS vaccines since the virus may spread from cell to cell without the virus entering the circulation.
Recombination and mutation of the vaccine virus in an attenuated vaccine.
Despite these problems, anti-viral vaccines have, in some cases, been spectacularly successful (figure 1) leading in one case (smallpox) to the elimination of the disease from the human population. The smallpox vaccine is an example of an attenuated vaccine, although not of the original pathogenic smallpox virus. Another successful vaccine is the polio vaccine which may lead to the elimination of this disease from the human population in a the next few years. This vaccine comes in two forms. The Salk vaccine is a killed vaccine while that developed by Sabin is a live attenuated vaccine. Polio is presently restricted to parts of Africa and south Asia.
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Content Reference:http://pathmicro.med.sc.edu/lecture/vaccines.htm
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