Escape of pathogens from the host immune response by mutations and mimicry. Possible means to improve vaccine performance.

The ability of certain pathogens, such as human immunodeficiency, hepatitis C, herpes simplex, influenza viruses, Plasmodium falciparum, etc., to escape from host immune response is generally ascribed to high mutation rate of their genome. We challenge this assumption and propose that molecular mimicry of host antigens by these pathogens could also participate to this resistance. Several studies show that there is no correlation between the mutation rate value of a pathogen and the possibility to develop an effective vaccine. On the other hand, pathogens which do not respond to vaccine are usually reported to display host protein mimicry. We propose to suppress in the thymus the epitopes of the self which are in common with the pathogen. This could be achieved by intrathymic injection of antibodies against this microorganism. These antibodies would be obtained by vaccination of a foreign animal species. It is expected that the negative selection of the CD4(+) and CD8(+) T lymphocytes specific for these epitopes would be prevented, that the number of epitopes recognized as foreign to the host would be increased and that the immune response diversity would be enhanced.