Safety and immunogenicity of a CTL multiepitope peptide vaccine for HIV with or without GM-CSF in a phase I trial.
There is an urgent need for a vaccine capable of preventing HIV infection or the development of HIV-related disease. A number of approaches designed to stimulate HIV-specific CD8+ cytotoxic T cell responses together with helper responses are presently under evaluation. In this phase 1, multi-center, placebo-controlled trial, we tested the ability of a novel multiepitope peptide vaccine to elicit HIV-specific immunity. To enhance the immunogenicity of the peptide vaccine, half of the vaccine recipients received recombinant granulocyte-macrophage colony stimulating factor (GM-CSF) protein as a coadjuvant. The vaccine was safe; tolerability was moderate, with a number of adverse events related to local injection site reactogenicity. Anti-GM-CSF antibody responses developed in the majority of GM-CSF recipients but were not associated with adverse hematologic events. The vaccine was only minimally immunogenic. Six of 80 volunteers who received vaccine developed HIV-specific responses as measured by interferon-gamma ELISPOT assay, and measurable responses were transient. This study failed to demonstrate that GM-CSF can substantially improve the overall weak immunogenicity of a multiepitope peptide-based HIV vaccine.
Spearman, P; Kalams, S; Elizaga, M; Metch, B; Chiu, Y-L; Allen, M; Weinhold, KJ; Ferrari, G; Parker, SD; McElrath, MJ; Frey, SE; Fuchs, JD; Keefer, MC; Lubeck, MD; Egan, M; Braun, R; Eldridge, JH; Haynes, BF; Corey, L; NIAID HIV Vaccine Trials Network,
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