A phase 1/2 study of a multiclade HIV-1 DNA plasmid prime and recombinant adenovirus serotype 5 boost vaccine in HIV-Uninfected East Africans (RV 172).
BACKGROUND
Human immunodeficiency virus (HIV) vaccine development remains a global priority. We describe the safety and immunogenicity of a multiclade DNA vaccine prime with a replication-defective recombinant adenovirus serotype 5 (rAd5) boost.


METHODS
The vaccine is a 6-plasmid mixture encoding HIV envelope (env) subtypes A, B, and C and subtype B gag, pol, and nef, and an rAd5 expressing identical genes, with the exception of nef. Three hundred and twenty-four participants were randomized to receive placebo (n=138), a single dose of rAd5 at 10(10) (n = 24) or 10(11) particle units (n = 24), or DNA at 0, 1, and 2 months, followed by rAd5 at either 10(10) (n= 114) or 10(11) particle units (n = 24) boosting at 6 months. Participants were followed up for 24 weeks after the final vaccination.


RESULTS
The vaccine was safe and well tolerated. HIV-specific T cell responses were detected in 63% of vaccinees. Titers of preexisting Ad5 neutralizing antibody did not affect the frequency and magnitude of T cell responses in prime-boost recipients but did affect the response rates in participants that received rAd5 alone (P = .037).


CONCLUSIONS
The DNA/rAd5 vaccination regimen was safe and induced HIV type 1 multi-clade T cell responses, which were not significantly affected by titers of preexisting rAd5 neutralizing antibody. Trial Registration. ClinicalTrials.gov identifier: NCT00123968 .
Kibuuka
Hannah
H
Makerere University Walter Reed Project, Kampala, Uganda.
Kimutai
Robert
R
Maboko
Leonard
L
Sawe
Fred
F
Schunk
Mirjam S
MS
Kroidl
Arne
A
Shaffer
Douglas
D
Eller
Leigh Anne
LA
Kibaya
Rukia
R
Eller
Michael A
MA
Schindler
Karin B
KB
Schuetz
Alexandra
A
Millard
Monica
M
Kroll
Jason
J
Dally
Len
L
Hoelscher
Michael
M
Bailer
Robert
R
Cox
Josephine H
JH
Marovich
Mary
M
Birx
Deborah L
DL
Graham
Barney S
BS
Michael
Nelson L
NL
de Souza
Mark S
MS
Robb
Merlin L
ML
D016915:AIDS Vaccines / Q000008:administration & dosage* / Q000009:adverse effects / Q000235:genetics / Q000276:immunology; D000256:Adenoviridae / Q000235:genetics / Q000276:immunology*; D000293:Adolescent; D000328:Adult; D000351:Africa, Eastern; D057134:Antibodies, Neutralizing / Q000097:blood / Q000276:immunology; D000914:Antibodies, Viral / Q000097:blood / Q000276:immunology; D000956:Antigens, Viral / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002478:Cells, Cultured; D004279:DNA, Viral / Q000235:genetics / Q000276:immunology*; D004311:Double-Blind Method; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D015658:HIV Infections / Q000276:immunology / Q000517:prevention & control*; D015497:HIV-1 / Q000235:genetics / Q000276:immunology*; D054298:Human Immunodeficiency Virus Proteins / Q000235:genetics / Q000276:immunology; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008297:Male; D008875:Middle Aged; D010957:Plasmids / Q000235:genetics / Q000276:immunology*; D019444:Vaccines, DNA / Q000008:administration & dosage* / Q000009:adverse effects / Q000235:genetics / Q000276:immunology; D055815:Young Adult
D016915:AIDS Vaccines; D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D000956:Antigens, Viral; D004279:DNA, Viral; D054298:Human Immunodeficiency Virus Proteins; D019444:Vaccines, DNA; D007371:Interferon-gamma