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.

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Frey, SE; Peiperl, L; McElrath, MJ; Kalams, S; Goepfert, PA; Keefer, MC; Baden, LR; Lally, MA; Mayer, K; Blattner, WA; Harro, CD; Hammer, SM; Gorse, GJ; Hural, J; Tomaras, GD; Levy, Y; Gilbert, P; deCamp, A; Russell, ND; Elizaga, M; Allen, M; Corey, L

Published Date

  • November 2014

Published In

Volume / Issue

  • 21 / 11

Start / End Page

  • 1589 - 1599

PubMed ID

  • 25253665

Pubmed Central ID

  • 25253665

Electronic International Standard Serial Number (EISSN)

  • 1556-679X

Digital Object Identifier (DOI)

  • 10.1128/CVI.00450-14

Language

  • eng

Conference Location

  • United States