Safety and immunogenicity of a replication-incompetent adenovirus type 5 HIV-1 clade B gag/pol/nef vaccine in healthy adults.
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 x 10(6) to 1 x 10(11) 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-gamma enzyme-linked immunosorbent spot response measured 4 weeks after administration of the last dose.


RESULTS
Of 259 randomized individuals, 257 (99%) received > or = 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 > or = 3 x 10(9) viral particles elicited positive enzyme-linked immunosorbent spot responses to > or = 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 x 10(10) 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.
Priddy
Frances H
FH
Department of Medicine, Emory University School of Medicine, Atlanta, Georgia, USA. fpriddy@emory.edu
Brown
Deborah
D
Kublin
James
J
Monahan
Kathleen
K
Wright
David P
DP
Lalezari
Jacob
J
Santiago
Steven
S
Marmor
Michael
M
Lally
Michelle
M
Novak
Richard M
RM
Brown
Stephen J
SJ
Kulkarni
Priya
P
Dubey
Sheri A
SA
Kierstead
Lisa S
LS
Casimiro
Danilo R
DR
Mogg
Robin
R
DiNubile
Mark J
MJ
Shiver
John W
JW
Leavitt
Randi Y
RY
Robertson
Michael N
MN
Mehrotra
Devan V
DV
Quirk
Erin
E
D016915:AIDS Vaccines / Q000008:administration & dosage / Q000009:adverse effects* / Q000276:immunology*; D000256:Adenoviridae; D000328:Adult; D005260:Female; D015685:Fusion Proteins, gag-pol / Q000276:immunology; D015750:Genes, gag; D015751:Genes, pol; D015483:HIV Antibodies / Q000096:biosynthesis; D015658:HIV Infections / Q000276:immunology / Q000517:prevention & control*; D015497:HIV-1 / Q000235:genetics / Q000276:immunology*; D006801:Humans; D008297:Male; D012449:Safety; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology
D016915:AIDS Vaccines; D015685:Fusion Proteins, gag-pol; D015483:HIV Antibodies; D019444:Vaccines, DNA