E-Letter responses to:

editorial: David Baltimore Steering a Course to an AIDS Vaccine Science 2002; 296: 2297 [Summary] [PDF]

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Antibodies and T cells: the heart and soul of the immune system.

Julia L. Hurwitz, Karen S. Slobod   (29 July 2002)

Antibodies and T cells: the heart and soul of the immune system. 29 July 2002
Julia L. Hurwitz, Immunologist St. Jude Children's Research Hospital, Karen S. Slobod Respond to this E-Letter: Re: Antibodies and T cells: the heart and soul of the immune system.	Dr. Baltimore's comment ("Steering a Course to an AIDS Vaccine") clearly summarizes the ongoing struggle to prevent HIV infection. He highlights a current question in the vaccine field: Can B cells and T cells ever sufficiently protect humans from HIV? We would like to respond with a firm "yes." Antibody-mediated prevention of infection by HIV and other immunodeficiency viruses has been demonstrated in numerous publications (1-3), and, as Dr. Baltimore notes, CD8+ T cells can eliminate immunodeficiency virus-infected cells. To aid B and T cells to prevent HIV infection in humans, we suggest that two issues be considered: (i) HIV is diverse. Our defenses against HIV, our B and T lymphocytes, are also diverse. A B cell (and its antibody) specific for one HIV determinant will not necessarily bind or neutralize HIV bearing a different determinant (4-6). Similarly, a T cell that can recognize one HIV sequence will not necessarily recognize HIV with a different sequence (as described by Dr. Baltimore in his discussion of viral escape). Accordingly, thwarting virus escape requires a priori priming of a breadth of specific B and T cells, collectively responsive to diverse virus structures. The target structures on HIV are finite in number, as even this highly variable retrovirus must assume conformations constrained by function (e.g., HIV must retain structures necessary to bind host cell membrane molecules). (ii) The immune system must be activated prior to virus exposure. The immune response elicited by HIV infection has been shown to prevent infections from exogenous sources (1, 2) but has never successfully purged virus from privileged sites. To address these points, we are testing a multienvelope vaccine in preclinical and clinical studies at St. Jude Children's Research Hospital (7). The vaccine is designed to represent viral diversity and activate heterogeneous B and T cells, surely required for the effective prevention of HIV infection in humans. Julia L. Hurwitz, Ph.D., and Karen S. Slobod, M.D. References (1) R. Shibata et al., Nature Med. 5, 204 (1999). (2) A. M. Prince et al., AIDS Res. Hum. Retroviruses 7, 971 (1991). (3) P. Putkonen et al., Nature 352, 436 (1991). (4) S. D'Costa, K. S. Slobod, R. G. Webster, S. W. White, J. L. Hurwitz, AIDS Res. Hum. Retroviruses 17(12), 1205 (2001). (5) B. A. Watkins et al., J. Virol. 67, 7493 (1993). (6) T. E. Caver, T. D. Lockey, R. V. Srinivas, R. G. Webster, J. L. Hurwitz, Vaccine 17, 1567 (1999). (7) T. D. Lockey et al., Immunol Res. 21(1), 7 (2000).