Phase I/II randomized trial of safety and immunogenicity of LIPO-5 alone, ALVAC-HIV (vCP1452) alone, and ALVAC-HIV (vCP1452) prime/LIPO-5 boost in healthy, HIV-1-uninfected adult participants.

Abstract

Finding an effective human immunodeficiency virus type 1 (HIV-1) vaccine remains a major global health priority. In a phase I/II, placebo-controlled trial, healthy, HIV-1-negative adults were randomized to receive one of 5 vaccine regimens: LIPO-5 (combination of 5 lipopeptides) alone (250 μg), ALVAC-HIV (vCP1452) alone, or 3 groups of ALVAC-HIV (vCP1452) followed by ALVAC-HIV (vCP1452) plus LIPO-5 (250, 750, and 2,500 μg). Only 73/174 participants (42%) received all four vaccinations due to a study halt related to myelitis. There were no significant differences in systemic reactions between groups or in local reactogenicity between groups receiving ALVAC-HIV (vCP1452). Significant differences in local reactogenicity occurred between groups receiving LIPO-5 (P ≤ 0.05). Gag and Env antibodies were undetectable by ELISA 2 weeks after the fourth vaccination for all but one recipient. Antibodies to Gag and Env were present in 32% and 24% of recipients of ALVAC-HIV (vCP1452) alone and in 47% and 35% of ALVAC-HIV (vCP1452)+LIPO recipients, respectively. Coadministration of LIPO-5 did not significantly increase the response rate compared to ALVAC-HIV (vCP1452) alone, nor was there a significant relationship between dose and antibody responses among ALVAC-HIV (vCP1452)+LIPO groups. Over 90% of study participants had no positive gamma interferon (IFN-γ) enzyme-linked immunosorbent spot assay (ELISpot) responses to any peptide pool at any time point. The study was halted due to a case of myelitis possibly related to the LIPO-5 vaccine; this case of myelitis remains an isolated event. In general, there was no appreciable cell-mediated immunity detected in response to the vaccines used in this study, and antibody responses were limited. The clinical trial is registered on ClinicalTrials.gov with registry number NCT00076063.

• Authors: Sharon E Frey, Laurence Peiperl, M Juliana McElrath, Spyros Kalams, Paul A Goepfert, Michael C Keefer, Lindsey R Baden, Michelle A Lally, Kenneth Mayer, William A Blattner, Clayton D Harro, Scott M Hammer, Geoffrey J Gorse, John Hural, Georgia D Tomaras, Yves Levy, Peter Gilbert, Allan deCamp, Nina D Russell, Marnie Elizaga, Mary Allen, Lawrence Corey
• Journal: Clinical and vaccine immunology : CVI (Clin Vaccine Immunol) Vol. 21 Issue 11 Pg. 1589-99 (Nov 2014) ISSN: 1556-679X [Electronic] United States
• PMID: 25253665 (Publication Type: Clinical Trial, Phase I, Clinical Trial, Phase II, Comparative Study, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
• Copyright: Copyright © 2014, American Society for Microbiology. All Rights Reserved.

Chemical References

• AIDS Vaccines
• HIV Antibodies
• Placebos
• Interferon-gamma

Topics

• AIDS Vaccines (administration & dosage, adverse effects, immunology)
• Acquired Immunodeficiency Syndrome (prevention & control)
• Adolescent
• Adult
• Drug-Related Side Effects and Adverse Reactions (epidemiology, pathology)
• Enzyme-Linked Immunosorbent Assay
• Enzyme-Linked Immunospot Assay
• Female
• HIV Antibodies (blood)
• HIV-1 (immunology)
• Humans
• Interferon-gamma (metabolism)
• Male
• Middle Aged
• Placebos (administration & dosage)
• Treatment Outcome
• Vaccination (adverse effects, methods)
• Young Adult