Asia (where most new strains of influenza arise) that put ducks, pigs, and farmers in close proximity may facilitate genetic shift in the virus (Scholtissek and Naylor, 1988; Langone, 1990; Morse, 1990). This theory is based on the idea that pigs have been infected by both an avian influenza virus and a human influenza virus. These viruses, while inside the pig, exchange genetic material, potentially resulting in a more virulent virus capable of initiating a pandemic if passed to humans.

To date, 14 distinct H and 9 distinct N influenza A antigens have been identified in birds and animals. Only three subtype combinations (representing three H and two N antigens) are known to cause disease in man: H1N1, H2N2, and H3N2. There have been two antigenic shifts in the influenza A virus since 1918: the first, in 1957, produced the H2N2 subtype; the second, in 1968, the H3N2 subtype. Antigenic drift and antigenic shift both challenge the immunity of human populations and require constant changes in the composition of influenza vaccine. Predicting the direction of these changes (based on worldwide surveillance data) is difficult.

Human Immunodeficiency Virus

A second example of RNA variability is HIV. HIV-1 and HIV-2, the two known HIV viruses, exhibit extensive genetic variability and exist in infected individuals as a complex mixture of closely related genomes, or quasispecies. These quasispecies undergo rapid genetic change such that the major viral form present in chronically infected persons differs over time. This continual change can result in alterations of those parts of the virus recognized by the human immune system; the effect of such alterations is to make the immune system less able to eliminate or suppress the virus.

It is likely that the extensive genetic variability of HIV-1 and HIV-2 will present major problems in the development of an effective vaccine. Because the differences between HIV-1 and HIV-2 are significant, a vaccine against one will probably not be effective against the other. More worrisome is the possibility that an HIV-1 or HIV-2 vaccine will not be effective against all quasispecies within that one subgroup. The quasispecies in any one person are closely related to each other but are different from those in someone else, raising the possibility that vaccines of different antigenic composition will be needed to prevent infection or disease in different individuals. Of additional concern is the fact that the majority of HIV isolates from other countries, such as Thailand and countries in Africa, differ substantially from strains found in the United States and Europe. It is highly probable that a widely effective HIV vaccine will need to be a composite of viral antigens from different regions of the globe or that multiple vaccines, targeted for specific regions, will need to be developed.



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