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316 HIV Neutralizing Antibodies in Seronegative Volunteers in a Phase I/II Prime-Boost Vaccine Trial in Thailand
V. Polonis*1, J. Kim1, S. Nittayaphan2, P. Pittisuttithum3, R. El Habib4, W. Heyward5, A. Brown2, J. McNeil1, D. Birx1, and the TAVEG6
1The US Military HIV Res. Prgm., Rockville, MD, USA; 2Armed Forces Res. Inst. of Med. Sci., Bangkok, Thailand; 3Vaccine Trial Ctr., Bangkok, Thailand; 4Aventis-Pasteur, Paris, France; 5VaxGen, Inc., Brisbane, CA; and 6Thai AIDS Vaccine Evaluation Grp., Thailand, USA, and France
Background: Measurement of HIV neutralizing antibody (NAb) is considered an important parameter of immunogenicity in evaluating candidate vaccines. The purpose of this study was to assess vaccine-induced NAb to subtypes B and CRF01_A/E (E) in an ongoing Phase I/II prime-boost trial comparing boost doses in Thailand.
Methods: HIV seronegative Thais in groups 1, 2, and 3 received ALVAC vCP1521 at weeks 0, 4, 12, and 24, while group 2 received low (200 mug) and group 3 standard (600 mug) boosts of AIDSVAX rgp120 B/E (VaxGen, Inc.) at weeks 12 and 24. There were 25% placebos in groups 2 and 3; the data remain blinded. Sera from 120 volunteers (at weeks 0 and 26(28) and 20 HIV-positive Thais were tested for HIV-1 NAb. A T-cell line (A3/R5-6) engineered to express the CCR5 coreceptor was used for adapted nonsyncytium inducing primary isolates. The reduction of p24 production by pre- and post-vaccination sera was compared in a standardized, acute infection neutralization assay.
Results: None of 5 Phase I open-label volunteers who received ALVAC alone (group 1) had NAb to 3 viruses tested. In group 2, 41 of 56 (73%) volunteers tested were NAb positive for HIV-1MN and 43 of 59 (73%) group 3 volunteers had NAb to HIV-1MN. NAb titers for patient sera ranged from <1:10 to >1:10,000. Using A3/R5-6 cells, NAb against the subtype E vaccine homologous virus, CM244, was measured. Whereas the MN NAb-negative volunteers (tested to date) were negative for subtype E Nab, a subset of MN positives show NAb to the CM244 and/or NP03 subtype E viruses. Preliminary data suggest increased responses to subtype E in group 3.
Conclusions: ALVAC (vCP1521) alone did not induce measurable NAb, whereas 73% of volunteers (vaccine and placebo recipients) in the groups receiving rgp120 boosts developed NAb to at least 1 virus. Broadly neutralizing antibody to subtype B and E adapted viruses was elicited only in rgp120 boosted subjects.
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