Safety and Immunogenicity of a CTL Multiepitope Peptide Vaccine for HIV with or without GM-CSF in a Phase I Trial

• Authors: Paul Spearman, Emory University; Spyros Kalams, Vanderbilt University; Marnie Elizaga, Fred Hutchinson Cancer Research Center; Barbara Metch, Fred Hutchinson Cancer Research Center; Ya-Lin Chiu, Fred Hutchinson Cancer Research Center; Mary Allen, Division of AIDS, NIAID, NIH; Kent J. Weinhold, Duke University; Guido Ferrari, Duke University; Scott D. Parker, University of Alabama; M. Juliana McElrath, Fred Hutchinson Cancer Research Center; Sharon E. Frey, Saint Louis University; Jonathan D. Fuchs, San Francisco Department of Public Health; Michael C. Keefer, University of Rochester; Michael D. Lubeck, Wyeth Vaccines Research; Michael Egan, Wyeth Vaccines Research; Ralph Braun, Wyeth Vaccines Research; John H. Eldridge, Wyeth Vaccines Research; Barton F. Haynes, Duke University School of Medicine; Lawrence Corey, Fred Hutchinson Cancer Research Center
• Journal Title: Vaccine
• Volume: Volume 27, Number 2
• Publisher: Elsevier: 12 months | 2009-01-07, Pages 243-249
• Type of Work: Article | Post-print: After Peer Review
• Publisher DOI: http://doi.org/10.1016/j.vaccine.2008.10.051
• Subjects: Health Sciences, Public Health; Health Sciences, General
• Keywords: HIV vaccine; Multiepitope peptide; GM-CSF; CD8+ cytotoxic T cells; Anti-GM-CSF antibody

Abstract

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 multi-epitope peptide vaccine to elicit HIV-specific immunity. To enhance the immunogenicity of the peptide vaccine, half of the vaccine recipients received recombinant GM-CSF protein as a co-adjuvant. 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.