AEGiS-14IAC: Cytotoxic T lymphocyte responses in participants enrolled in a phase I/II canarypox (ALVAC)/ gp120 B/E prime-boost HIV vaccine trial in Thailand.

14th International AIDS Conference

Barcelona, Spain - July 7-12, 2002

Cytotoxic T lymphocyte responses in participants enrolled in a phase I/II canarypox (ALVAC)/ gp120 B/E prime-boost HIV vaccine trial in Thailand.

Int Conf AIDS 2002 Jul 7-12; 14:(abstract no. LbOr14)

de Souza M, Karnasuta C, Cox J, Nitayaphan S, Pittisituttithum P, Brown A, Gurunathan S, Heyward W, McNeil J, Birx D
AFRIMS, Bangkok, Thailand

BACKGROUND: The frequency of cytotoxic T lymphocyte (CTL) responses was determined in HIV-seronegative recipients of canarypox (ALVAC-vCP1521) expressing HIV subtype E Env and B Gag/Pro and HIV recombinant bivalent gp120 (AIDSVAX é « B/E) as a boost.

METHODS: The injection regimen was 0, 1, 3 and 6 months. Five subjects were initially enrolled in an open-label study to assess the safety of ALVAC-vCP1521 (Aventis Pasteur, Lyon, France). Volunteers in phase II were randomly assigned into 3 groups. Group I (N=30) received placebo; Groups II (N=45) and III (N=45) received ALVAC-vCP1521. Groups II and III received a boost of 200 é g and 600 é g of AIDSVAX é « B/E (VaxGen, Inc., Brisbane, USA), respectively. CTL assays using chromium release were conducted from baseline through 6 months following completion of immunisations. Freshly isolated PBMC were stimulated in vitro with clade E and B antigens and used as effectors with autologous B cells infected with recombinant vaccinia viruses expressing clade E Env and clade B Gag/Pol antigens as targets. CD8 specificity of a positive CTL response was assessed.

RESULTS: CTL responses conducted at baseline on 121 volunteers were uniformly negative. The cumulative prevalence of HIV-specific CD8+ CTL activity in the ALVAC group was 24% (22/93). No placebo recipients demonstrated CTL activity. Initial positive CTL responses were observed as early as two weeks following the second injection (3%), and as late as 6 months following the fourth-injection. The time-point with the greatest CTL activity was 6 months following the last injection (11%). CTL responses were observed to both Env and Gag/Pol antigens. Cross-clade CTL responses to subtype E Gag antigen were observed in 3/8 subjects tested.

CONCLUSION: ALVAC-vCP1521 is capable of inducing intra- and inter-clade CTL activity, thus supporting its use as a phase III vaccine candidate in Thailand where two HIV subtypes are circulating.

Keywords: AEGIS, AIDS Vaccines, T-Lymphocytes, Cytotoxic, HIV Antigens, HIV Infections, Gene Products, gag, HIV Envelope Protein gp120, HIV, HIV Envelope Protein gp160, HIV Antibodies, Vaccinia virus, HIV Seronegativity, Thailand, HIV Seropositivity, France, AIDSVAX, In Vitro, immunology

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