Grouppe Kurosawa: HIV - Conclusion (print)

Conclusion

Although it appears counter intuitive, we believe the only immune response that should be mounted against the HIV membrane protein gp160/gp120 is one of immunological tolerance. This protein should be cloned into an appropriate plant and fed to people at greatest risk. Oral tolerance to gp160/gp120 would go a long way toward diminishing many of the immunological disorders associated with HIV infections. This disorders fall into two categories.

1. Autoimmune crossreactivity, as previously discussed.
2. Anti-gp160/gp120 antibody immune complexes that bind complement receptors on macrophages and dendritic cells. These immune complexes inappropriately crosslink CD4 on normal T and B cells thereby inducing apoptosis, especially in the lymph nodes.

The humoral immune response against the gp160/gp120 membrane protein of HIV is fundamental to the development of the clinical syndrome we call AIDS. It doesn't make any difference if the virus is infectious or not. Granted, immunosuppressive proteins such as TAT, NEF and VPR substantially contribute to the overall state of immune dysfunction associated with AIDS, but it is the humoral immune response to gp160/gp120 that can deplete the CD4 T cell population the fastest. As an example, in mice transgenic for the human CD4 molecule, immunization with purified gp120 depletes the CD4 T cell population 7 fold, and the B cell population 3 fold in 6 days. These mice have never been exposed to the HIV virus. The CD4 T cell depletion is strictly mediated by anti-gp120 antibodies (Kang, Y., et al. An ongoing immune response to HIV envelope gp120 in human CD4-transgenic mice contributes to T cell decline upon intravenous administration of gp120. Eur. J. Immunol. 28:2253, 1998). Clearly, the HIV vaccines in development that target the gp160/gp120 protein will not only fail to protect against a subsequent viral infection, they will actually promote the depletion of normal CD4 T cells. This is not an exaggerated statement. In 1996, a study was published in PNAS (McElrath, M. Juliana, et al. Human immunodeficiency virus type 1 infection despite prior immunization with a recombinant envelope vaccine regimen. Proc. Natl. Acad. Sci. 93:3972, 1996) that carefully chronicled the immunization and anti-HIV immune responses of a volunteer that had been immunized with an experimental HIV vaccine. The subject was immunized over a period of four years-three times with a live recombinant vaccinia virus containing gp160 sequences, and three times with recombinant gp160 protein. Ten weeks after the last vaccinia virus booster immunization, the subject had unprotected sex with a new partner and became infected with the HIV virus. The subject had previously demonstrated the presence of both neutralizing antibody and strong T cell responses against the virus in in vitro assays. He became infected anyway. The most significant aspect of this study is the rapidity by which this subject became gravely ill. Within two years of infection, the subject's CD4 T cell count fell to 250. This is an extremely rapid disease progression, and we believe it is entirely due to immunization with the gp160 protein. There is no such thing as a true neutralizing immune response against the HIV membrane protein gp160/gp120. It is a contradiction in terms. In vitro studies of viral neutralization are meaningless predictors of vaccine efficacy. Any attempt to induce a vaccine-mediated humoral immune response to gp160/gp120 will invariably prove fatal to the recipient. Studies in chimpanzees that purport to demonstrate the efficacy of anti-gp160/gp120 protein vaccines are all fatally flawed in design. The challenge stocks of virus used in these studies are almost always prepared with human cell lines. The chimpanzees respond vigorously to the human histocompatibility antigens on the membranes of the virus particles-not the presence of viral associated gp160. For further information on this topic, read the essay Why Current HIV Vaccines Will Fail.

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