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8th Conference on Retroviruses and Opportunistic Infections
Chicago, IL - February 4 - 8, 2001
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Induction of mucosal CTL and their role in resistance against viral transmission
Conf Retroviruses Opportunistic Infect 2001 Feb 4-8; 8:281 (abstract no. S5)
Belyakov IM, Hel Z, Kelsall B, Ahlers JD, Nacsa J, Watkins DI, Allen TM, Sette A, Altman J, Woodward R, Markham P, Clements JD, Kuznetsov VA, Earl P, Moss B, Franchini G, Strober W, Berzofsky JA; NCI, NIH, Bethesda, MD.
We have examined the role of CTL induced by mucosal vaccines in protection against mucosal transmission of viruses in a murine model and in an SHIV-macaque model. Mice immunized intrarectally with a peptide HIV vaccine containing helper and CTL epitopes produced CTL in the Peyer's patches and lamina propria of the intestine as well as the spleen and were resistant to mucosal transmission of a recombinant vaccinia virus expressing HIV-1 gp160. In contrast, mice immunized s.c. with the same peptide produced CTL in the spleen but not in the mucosal sites and were not resistant to mucosal transmission of the virus. The protection was dependent on CD8+ cells as shown by in vivo depletion studies. Thus, protection against mucosal transmission required CTL to be present at the mucosal site of transmission. To translate this to a retroviral challenge model in macaques, we immunized MamuA*01 Rhesus macaques with a similar peptide vaccine including 3 SIV gag and pol epitopes presented by MamuA*01. Intrarectally immunized animals made CTL in the colon and mesenteric lymph nodes which correlated with T-proliferative responses induced, suggesting a role for CD4 help in CTL induction. After intrarectal challenge with pathogenic SHIV- ku, the intrarectally immunized animals showed a more complete clearance of virus and a better preservation of CD4 cell numbers than animals immunized s.c. with the same peptide or adjuvant- only controls. Immunized animals also made stronger CTL responses after infection, indicating the induction of memory CTL. We conclude that in mice and primates, induction of mucosal CTL may be critical for a vaccine to prevent or ameliorate virus infection transmitted through a mucosal route.
Keywords: AEGIS, AIDS Vaccines, SIV, Vaccinia virus, HIV Envelope Protein gp160, Macaca mulatta, HIV, Macaca, Peyer's Patches, Animal, Mice, transmission, virology, AIDS
2001-02-04
S5
Copyright © 2001 - Foundation for Retrovirology and Human Health. Reproduction of this abstract (other than one copy for personal reference) must be cleared through the Foundation for Retrovirology and Human Health. Licensed (AIDSLINE) from National Library of Medicine.