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

Clin Vaccine Immunol. 2014 Nov;21(11):1589-99. doi: 10.1128/CVI.00450-14. Epub 2014 Sep 24.

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.

Publication types

  • Clinical Trial, Phase I
  • Clinical Trial, Phase II
  • Comparative Study
  • 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.

MeSH terms

  • AIDS Vaccines / administration & dosage
  • AIDS Vaccines / adverse effects*
  • AIDS Vaccines / immunology*
  • Acquired Immunodeficiency Syndrome / prevention & control*
  • Adolescent
  • Adult
  • Drug-Related Side Effects and Adverse Reactions / epidemiology
  • Drug-Related Side Effects and Adverse Reactions / 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*
  • Vaccination / methods*
  • Young Adult

Substances

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

Associated data

  • ClinicalTrials.gov/NCT00076063

Grants and funding