Testing The True Potential of CD8 T cells to Protect against Immunodefinciency Virus Infection via Novel Vaccination
Immunological memory protexts the vertebrate host from re-infection from microbial pathogens. Vaccines attempt to elicit protective memory while avoiding the potentially deleterious effects of natural infection. Most vaccines only stimulate the humoral arm (referring to B cells that produce antibody) of the adaptive immune system, although this is often sufficient to afford protection against natural infection. Difficulties generating effective neutralizing antibodies, and evidence that cellular immunity (referring to CD8 T cells that contribute to the control of many naturally acquired viral infections) is critical for resistance against immunodeficiency viruses, have provided a sensible rationale for shifting HIV vaccine development towards generating 'goog' CD8 T cell immunity. The best vaccination strategies generate only 100-1000 specific memory CD8 T cells per million lymphocytes in blood. These strategies have failed to protect the host against HIV in human clinical trials. We have developed a novel vaccination strategy in mic that results in the largest levels of CD8 T cell memory ever visualized in the mammalian organism. For comparison, these levels of CD8 T cell memory are almost 1000 - fold greater than that elicited by current vaccines. We will test two hypotheses. Firstly, that the principals we have established in mice will translate to non-human primates, and a similar vaccination strategy will result in 100 - 1000 fold higher frequencies of SIV-Gag specific CD8 T cell memory in Rhesus macaques than achieved by other vaccination protocols in current use. Secondly, if SIV-Gag specific memory CD8 T cells are present at these frequencies, we will determine whether they will protect against SIV. If successful, thhis proposal will demonstrate if a CD8 T cell vaccine against HIV/SIV is possible.
Arnold O. Beckman exemplifies the meaning of the word humanitarian. Combined with his unwavering enthusiasm for life, his keen sense of humor and his strong moral and ethical principles, he is a national icon.