AEGiS-13IAC: Induction of gag and env specific CTL activity among recipients of X4 HIV vaccines correlates with development of In vitro resistance to R5 HIV-1BaL.

13th International AIDS Conference

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

Induction of gag and env specific CTL activity among recipients of X4 HIV vaccines correlates with development of In vitro resistance to R5 HIV-1BaL.

Int Conf AIDS 2000 Jul 9-14; 13:(abstract no. MoOrA220)

Schwartz D, Weinhold K, Castillo R, John R, Arango-Jaramillo S
D. Schwartz, Johns Hopkins University, Dept. of MMI, 615 N. Wolfe St., Baltimore, MD 21205, United States, Tel.: +1410 955 3175, Fax: +1410 955 0105, E-mail: dschwart@jhsph.edu

BACKGROUND: We have developed an assay in which PBMC resistance to CCR5 tropic (R5) HIV-1BaL challenge correlates with naturally acquired resistance in vivo. This assay has been validated in long term non progressors, exposed uninfected, and HIV-2 infected individuals. We have now extended this assay to all volunteers in AVEG vaccine protocols 022 and 022A.

METHODS: Participants in protocols 022 (n = 20) and 022A (n = 77) received 2-6 vaccinations with ALVAC vCP205 canarypox vector vaccine (Pasteur Merieux Connaught, France) containing env (MN/LAI), gag (LAI), and pol (LAI). In addition, vaccinees received 0-2 SF2 rgp120 boosts (Chiron, California). Vaccinees were assayed at month 10 of the study. Odds ratios, 95% confidence intervals, and p-values were determined using logistic regression analysis.

RESULTS: Contemporaneous CTL activity was associated with a 2.3 fold increase in the likelihood of resistance (95% C.I.:1.6,3.5; p > 0.001). Two contemporaneous CTL specificities, env and gag, were each independently associated with a 2.1 (95% C.I.:1.2,3.5; p > 0.01) and 1.8 (95% C.I.:1.0,3.1; p > 0.05) fold increased likelihood of resistance, respectively. Surprisingly, pol specific CTL activity did not significantly associate with in vitro resistance.

CONCLUSIONS: These data indicate that a previously validated in vitro correlate of naturally acquired resistance to HIV was also induced by vaccination with a multigene ALVAC vector. The fact that resistance to an R5 virus, typical of transmitted primary isolates, was generated by vaccine products derived from X4 strains has encouraging implications for vaccine development. Current studies focus on mechanism and specificity of the protective response. For example, it will be important to confirm in larger samples the lack of pol associated resistance. Such detailed information could guide vaccine design.

Keywords: AEGIS, AIDS Vaccines, HIV, HIV Infections, HIV Envelope Protein gp120, HIV Antibodies, HIV Envelope Protein gp160, HIV Seropositivity, HIV Antigens, HIV Core Protein p24, HIV-2, California, France, In Vitro, immunology
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