AEGiS-13IAC: Systemic and mucosal immunity in HIV-1 vaccine recipients.

13th International AIDS Conference

Durban, South Africa - July 9-July 14, 2000

Systemic and mucosal immunity in HIV-1 vaccine recipients.

Int Conf AIDS 2000 Jul 9-14; 13:(abstract no. WeOrC554)

Musey LK, Ha R, Galloway C, Tabet S, Ding Y, Belshe R, Celum C, McElrath MJ
L. K. Musey, University of Washington /FHCRC, Program in Infectious Diseases, 1100 Fairview Avenue North D3-100, Seattle, WA 98109, United States, Tel.: +1 206 667 67 39, Fax: +1 206 667 44 11, E-mail: luwy@u.washington.edu

BACKGROUND: HIV-specific T cells have been shown to play a critical role in control of viral replication. These effector cells may be important to elicit with immunization, both systemically and locally at sites where transmission most often occurs.Thus far, mucosal T cell responses have not been examined in HIV-uninfected vaccinees. We undertook a study to examine a subset of volunteers enrolled in a phase II trial in which both immunogens, canarypox vector and subunit gp120, were administered systemically.

METHODS: Twelve HIV-uninfected volunteers were immunized at days 0, 28, 84 and 168 with a live canarypox recombinant ALVAC-HIV (vCP205) containing HIV-env, and gag-prot genes (7 subjects)with or without HIV-SF2 rgp120 or the control pareparation (5 subjects). We prospectively evaluated T cell responses in blood, rectum and cervix at 3, 6 and 9 months after the last immunization. HIV-specific CTL were measured by conventional 51Cr release assay and/or IFN-g ELISPOT.

RESULTS: No HIV-specific CTL were detected in blood or mucosal tissues from 5 of 5 volunteers receiving the control regimen. Among subjects receiving vaccine, HIV-1 Env- and/or Gag-specific CTL were detected at one or more time points in PBMC and mucosal tissues from 5/7(71%) and 4/7(57%), respectively. The effectors were predominantly CD8+ T cells, although CD4+ T cell responses were observed. Responses were confirmed by IFN-g ELISpot in selected subjects. CTL clones were established from both compartments, and similar MHC restriction patterns and epitope recognition were found. In one individual, HIV-specific CTL responses persisted in the blood and mucosa up to 6 months after the last immunization.

CONCLUSION: Our results provide the first demonstration that HIV vaccine regimens delivered systemically can induce mucosal HIV-specific CTL. The presence of these effector cells in the rectal and cervical tissue, the major site of HIV entry, may be critical for viral control in these mucosal sites. Their role in preventing HIV-1 transmission through mucosal routes remains to be established.

Keywords: AEGIS, AIDS Vaccines, Immunity, Mucosal, HIV-1, HIV Infections, CD8-Positive T-Lymphocytes, T-Lymphocytes, Antigens, CD4, HIV Seropositivity, Vaccination, Female, immunology
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