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Safety and immunogenicity of a CTL multiepitope peptide vaccine for HIV with or without GM-CSF in a phase I trial

2008; Elsevier BV; Volume: 27; Issue: 2 Linguagem: Inglês

10.1016/j.vaccine.2008.10.051

1873-2518

Paul Spearman, Spyros A. Kalams, Marnie Elizaga, Barbara Metch, Ya-Lin Chiu, Mary Allen, Kent J. Weinhold, Guido Ferrari, Scott Parker, M. Juliana McElrath, Sharon E. Frey, Jonathan D. Fuchs, Michael C. Keefer, Michael D. Lubeck, Michael A. Egan, Ralph P. Braun, John H. Eldridge, Barton F. Haynes, Lawrence Corey,

Immune Cell Function and Interaction

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.