What is the Vaccine?

Vaccines 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.

All Vaccinations Work by presenting a foreign antigen to the immune system in order to evoke an immune response, but there are several ways to do this. The three main types are as follows:
- An inactivated vaccine consists of virus particles which are grown in culture and then killed using a method such as heat or formaldehyde. The virus particles are destroyed and cannot replicate, but the virus capsid proteins are intact enough to be recognized by the immune system and evoke a response. When manufactured correctly, the vaccine is not infectious, but improper inactivation can result in intact and infectious particles. Since the properly produced vaccine does not reproduce, booster shots are required periodically to reinforce the immune response.
- In an attenuated vaccine, live virus particles with very low virulence are administered. They will reproduce, but very slowly. Since they do reproduce and continue to present antigen beyond the initial vaccination, boosters are required less often. These vaccines are produced by growing the virus in tissue cultures that will select for less virulent strains or by mutagenesis or targeted deletions in genes required for virulence. There is a small risk of reversion to virulence; this risk is smaller in vaccines with deletions. Attenuated vaccines also cannot be used by immunocompromised individuals.
- A subunit vaccine presents an antigen to the immune system without introducing viral particles, whole or otherwise. One method of production involves isolation of a specific protein from a virus and administering this by itself. A weakness of this technique is that isolated proteins can be denatured and will then bind to different antibodies than the proteins in the virus. A second method of subunit vaccine is the recombinant vaccine, which involves putting a protein gene from the targeted virus into another virus. The second virus will express the protein, but will not present a risk to the patient.
- 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 UK and South Asia.