Journal Article

Safety and Immunogenicity of a Replication-Incompetent Adenovirus Type 5 HIV-1 Clade B <i>gag/pol/nef</i> Vaccine in Healthy Adults

Frances H. Priddy, Deborah Brown, James Kublin, Kathleen Monahan, David P. Wright, Jacob Lalezari, Steven Santiago, Michael Marmor, Michelle Lally, Richard M. Novak, Stephen J. Brown, Priya Kulkarni, Sheri A. Dubey, Lisa S. Kierstead, Danilo R. Casimiro, Robin Mogg, Mark J. DiNubile, John W. Shiver, Randi Y. Leavitt, Michael N. Robertson, Devan V. Mehrotra and Erin Quirk

in Clinical Infectious Diseases

Published on behalf of Infectious Diseases Society of America

Volume 46, issue 11, pages 1769-1781
Published in print June 2008 | ISSN: 1058-4838
Published online June 2008 | e-ISSN: 1537-6591 | DOI: https://dx.doi.org/10.1086/587993
Safety and Immunogenicity of a Replication-Incompetent Adenovirus Type 5 HIV-1 Clade B gag/pol/nef Vaccine in Healthy Adults

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Background. The safety and immunogenicity of the MRK adenovirus type 5 human immunodeficiency virus type 1 clade B gag/pol/nef vaccine, a replication-incompetent adenovirus type 5—vectored vaccine designed to elicit cell-mediated immunity against conserved human immunodeficiency virus proteins, was assessed in a phase 1 trial.

Methods. Healthy adults not infected with human immunodeficiency virus were enrolled in a multicenter, dose-escalating, blind, placebo-controlled study to evaluate a 3-dose homologous prime-boost regimen of the trivalent MRK adenovirus type 5 human immunodeficiency virus type 1 vaccine containing from 3×106 to 1×1011 viral particles per 1-mL dose administered on day 1, during week 4 and during week 26. Adverse events were recorded for 29 days after each intradeltoid injection. The primary immunogenicity end point was the proportion of study participants with a positive unfractionated Gag-, Pol-, or Nef-specific interferon-γ enzyme-linked immunosorbent spot response measured 4 weeks after administration of the last dose.

Results. Of 259 randomized individuals, 257 (99%) received ⩾1 dose of vaccine or placebo and were included in the safety analyses. Enzyme-linked immunosorbent spot results were available for 217 study participants (84%) at week 30. No serious vaccine-related adverse events occurred. No study participant discontinued participation because of vaccine-related adverse events. The frequency of injection-site reactions was dose dependent. Vaccine doses of ⩾3×109 viral particles elicited positive enzyme-linked immunosorbent spot responses to ⩾1 vaccine component in >60% of recipients. High baseline antibody titers against adenovirus type 5 diminished enzyme-linked immunosorbent spot responses at all doses except the 3×1010 viral particle dose.

Conclusions. The vaccine was generally well tolerated and induced cell-mediated immune responses against human immunodeficiency virus type 1 peptides in most healthy adults. Despite these findings, vaccination in a proof-of-concept trial with use of this vaccine was discontinued because of lack of efficacy.

Journal Article.  6550 words.  Illustrated.

Subjects: Infectious Diseases ; Immunology ; Public Health and Epidemiology ; Microbiology

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