Immunity, immunopathology and vaccines against HIV?

Immunity and immunopathology of HIV infections leading to AIDS are reviewed from an evolutionary point of view. Accordingly infectious agents and host defences have co-evolved to reach balanced states where virus and host survive. While HIV has not quite yet reached an optimal balance, tuberculosis (TB), leprosy, HBV, HCV in humans or lymphocytic choriomeningitis virus (LCMV) in mice have successfully established persistence. These non- or poorly-cytopathic infections infect the next host usually before or at birth while hosts are immunoincompetent. They also infect immunocompetent hosts to persist at low levels concomitant with an ongoing T and B cell immune response that is repeatedly triggered by latent or persistent infection of extralymphatic or lymphatic host cells. This infectious or infection-immunity is the basis for cellular immunoprotection by antigen activated T cells. Because we cannot imitate this infection-immunity long-term and cannot build polyspecific vaccine combinations covering all possible neutralising variants yet, vaccines against TB, leprosy, HCV and HIV only protect transiently and incompletely.

Expression of the B-cell and T-cell epitopes of the rabies virus nucleoprotein in Mycobacterium bovis BCG and induction of an humoral response in mice.

Expression vectors containing rabies virus nucleoprotein B-cell and T-cell epitopes in Mycobacterium bovis BCG were constructed. The epitopes were subcloned into the M. leprae 18-kDa gene to ensure correct presentation to the host immune system. Expression of the 18-kDa::B+T epitope fusion protein was driven by either the hsp60 promoter, which is constitutively activated at a high level in M. bovis BCG, or the 18-kDa promoter, which is strongly induced in vivo. Mice were immunised intra-peritoneally with the recombinant BCG cultures and compared to a control group vaccinated with the commercial rabies vaccine Rai-SAD. Both of the expression vectors elicited a higher antibody titre than that of the rabies vaccine, with the highest response shown by M. bovis BCG (pUP203), expression controlled by the 18-kDa promoter. Immunisation with M. bovis BCG (pUP202), expression controlled by the hsp60 promoter, resulted in a continuously increasing antibody titre up to 60 days post immunisation. The mice antibodies were also capable of recognising the whole rabies virus and not only the synthetic peptide epitopes.