Safety and immunogenicity study of Multiclade HIV-1 adenoviral vector vaccine alone or as boost following a multiclade HIV-1 DNA vaccine in Africa.
BACKGROUND
We conducted a double-blind, randomized, placebo-controlled Phase I study of a recombinant replication-defective adenovirus type 5 (rAd5) vector expressing HIV-1 Gag and Pol from subtype B and Env from subtypes A, B and C, given alone or as boost following a DNA plasmid vaccine expressing the same HIV-1 proteins plus Nef, in 114 healthy HIV-uninfected African adults.


RESULTS
Volunteers were randomized to 4 groups receiving the rAd5 vaccine intramuscularly at dosage levels of 1×10(10) or 1×10(11) particle units (PU) either alone or as boost following 3 injections of the DNA vaccine given at 4 mg/dose intramuscularly by needle-free injection using Biojector® 2000. Safety and immunogenicity were evaluated for 12 months. Both vaccines were well-tolerated. Overall, 62% and 86% of vaccine recipients in the rAd5 alone and DNA prime - rAd5 boost groups, respectively, responded to the HIV-1 proteins by an interferon-gamma (IFN-γ) ELISPOT. The frequency of immune responses was independent of rAd5 dosage levels. The highest frequency of responses after rAd5 alone was detected at 6 weeks; after DNA prime - rAd5 boost, at 6 months (end of study). At baseline, neutralizing antibodies against Ad5 were present in 81% of volunteers; the distribution was similar across the 4 groups. Pre-existing immunity to Ad5 did not appear to have a significant impact on reactogenicity or immune response rates to HIV antigens by IFN-γ ELISPOT. Binding antibodies against Env were detected in up to 100% recipients of DNA prime - rAd5 boost. One volunteer acquired HIV infection after the study ended, two years after receipt of rAd5 alone.


CONCLUSIONS
The HIV-1 rAd5 vaccine, either alone or as a boost following HIV-1 DNA vaccine, was well-tolerated and immunogenic in African adults. DNA priming increased the frequency and magnitude of cellular and humoral immune responses, but there was no effect of rAd5 dosage on immunogenicity endpoints.


BACKGROUND
ClinicalTrials.gov NCT00124007.
Jaoko
Walter
W
Kenya AIDS Vaccine Initiative (KAVI), Nairobi, Kenya.
Karita
Etienne
E
Kayitenkore
Kayitesi
K
Omosa-Manyonyi
Gloria
G
Allen
Susan
S
Than
Soe
S
Adams
Elizabeth M
EM
Graham
Barney S
BS
Koup
Richard A
RA
Bailer
Robert T
RT
Smith
Carol
C
Dally
Len
L
Farah
Bashir
B
Anzala
Omu
O
Muvunyi
Claude M
CM
Bizimana
Jean
J
Tarragona-Fiol
Tony
T
Bergin
Philip J
PJ
Hayes
Peter
P
Ho
Martin
M
Loughran
Kelley
K
Komaroff
Wendy
W
Stevens
Gwynneth
G
Thomson
Helen
H
Boaz
Mark J
MJ
Cox
Josephine H
JH
Schmidt
Claudia
C
Gilmour
Jill
J
Nabel
Gary J
GJ
Fast
Patricia
P
Bwayo
Job
J
D016915:AIDS Vaccines / Q000009:adverse effects* / Q000276:immunology*; D000256:Adenoviridae / Q000235:genetics / Q000276:immunology*; D000293:Adolescent; D000328:Adult; D000914:Antibodies, Viral / Q000276:immunology; D004311:Double-Blind Method; D064420:Drug-Related Side Effects and Adverse Reactions; D005822:Genetic Vectors / Q000009:adverse effects / Q000235:genetics / Q000276:immunology*; D015658:HIV Infections / Q000276:immunology* / Q000517:prevention & control / Q000821:virology; D015497:HIV-1 / Q000145:classification / Q000235:genetics / Q000276:immunology; D006801:Humans; D007117:Immunization, Secondary; D008297:Male; D008875:Middle Aged; D019444:Vaccines, DNA / Q000009:adverse effects / Q000276:immunology*; D055815:Young Adult; D054301:gag Gene Products, Human Immunodeficiency Virus / Q000009:adverse effects / Q000235:genetics / Q000276:immunology; D054302:pol Gene Products, Human Immunodeficiency Virus / Q000009:adverse effects / Q000235:genetics / Q000276:immunology
D016915:AIDS Vaccines; D000914:Antibodies, Viral; D019444:Vaccines, DNA; D054301:gag Gene Products, Human Immunodeficiency Virus; D054302:pol Gene Products, Human Immunodeficiency Virus