112 CTLs: All T Cells Are Not Created Equal M Juliana McElrath Fred Hutchinson Cancer Res Ctr and Univ of Washington, Seattle, USA

Vaccines that prevent HIV-1 infection will likely need to elicit both broadly neutralizing antibodies and T cells, particularly HIV-1-specific CD8+ cytotoxic T lymphocytes (CTL).  Functionally intact CTL are required for the successful control of HIV-1 infection, and rapid CTL effectors at the site of initial infection may ultimately provide the best benefit.  Numerous vaccine strategies are being tested in clinical trials to elicit HIV-1-specific CTL.  Immunization with replication-incompetent adenovirus vectors with or without recombinant DNA priming has successfully induced both CD4+ helper and CD8+ CTL responses in the majority of those immunized.  Thus far, this approach has outperformed poxvectors and other multimodality regimens in generating CTL in human trials.  Vaccine-induced CTL, similar to persons with acute infection, maintain proliferative capacity and secrete IFN-g and IL-2.  However, it is unclear if such responses will be sufficient to rapidly accumulate at sites of infection and suppress viral replication in early target cells.  Moreover, persons with previous immunity to adenovirus serotype 5 may limit the utility of repeated boosting with these vectors in diverse populations.  Another consideration in the design of CTL-based vaccines is their ability to induce CTL that may result in escape mutations that hold a fitness cost for the virus.  Nonetheless, novel strategies to elicit HIV-1-specific CTL in HIV-1 seronegative persons hold promise in lowering the viral burden upon subsequent infection.