Safety and immunogenicity of a replication-defective adenovirus type 5 HIV vaccine in Ad5-seronegative persons: a randomized clinical trial (HVTN 054).
BACKGROUND
Individuals without prior immunity to a vaccine vector may be more sensitive to reactions following injection, but may also show optimal immune responses to vaccine antigens. To assess safety and maximal tolerated dose of an adenoviral vaccine vector in volunteers without prior immunity, we evaluated a recombinant replication-defective adenovirus type 5 (rAd5) vaccine expressing HIV-1 Gag, Pol, and multiclade Env proteins, VRC-HIVADV014-00-VP, in a randomized, double-blind, dose-escalation, multicenter trial (HVTN study 054) in HIV-1-seronegative participants without detectable neutralizing antibodies (nAb) to the vector. As secondary outcomes, we also assessed T-cell and antibody responses.


RESULTS
Volunteers received one dose of vaccine at either 10(10) or 10(11) adenovector particle units, or placebo. T-cell responses were measured against pools of global potential T-cell epitope peptides. HIV-1 binding and neutralizing antibodies were assessed. Systemic reactogenicity was greater at the higher dose, but the vaccine was well tolerated at both doses. Although no HIV infections occurred, commercial diagnostic assays were positive in 87% of vaccinees one year after vaccination. More than 85% of vaccinees developed HIV-1-specific T-cell responses detected by IFN-γ ELISpot and ICS assays at day 28. T-cell responses were: CD8-biased; evenly distributed across the three HIV-1 antigens; not substantially increased at the higher dose; and detected at similar frequencies one year following injection. The vaccine induced binding antibodies against at least one HIV-1 Env antigen in all recipients.


CONCLUSIONS
This vaccine appeared safe and was highly immunogenic following a single dose in human volunteers without prior nAb against the vector.


BACKGROUND
ClinicalTrials.gov NCT00119873.
University of California San Francisco, San Francisco, California, United States of America.
Laurence
L
Peiperl
Cecilia
C
Morgan
Zoe
Z
Moodie
Hongli
H
Li
Nina
N
Russell
Barney S
BS
Graham
Georgia D
GD
Tomaras
Stephen C
SC
De Rosa
M Juliana
MJ
McElrath
D016915:AIDS Vaccines / Q000009:adverse effects*; D000256:Adenoviridae / Q000276:immunology*; D000328:Adult; D057134:Antibodies, Neutralizing / Q000276:immunology; D003673:Defective Viruses / Q000276:immunology*; D004311:Double-Blind Method; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D008297:Male; D010919:Placebos; D013601:T-Lymphocytes / Q000276:immunology
D016915:AIDS Vaccines; D057134:Antibodies, Neutralizing; D010919:Placebos