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

FH Priddy, D Brown, J Kublin… - Clinical infectious …, 2008 - academic.oup.com
FH Priddy, D Brown, J Kublin, K Monahan, DP Wright, J Lalezari, S Santiago, M Marmor
Clinical infectious diseases, 2008academic.oup.com
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 …
Abstract
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.
Oxford University Press