Adenovirus vector-induced immune responses in nonhuman primates: responses to prime boost regimens.
In the phase IIb STEP trial an HIV-1 vaccine based on adenovirus (Ad) vectors of the human serotype 5 (AdHu5) not only failed to induce protection but also increased susceptibility to HIV-1 infection in individuals with preexisting neutralizing Abs against AdHu5. The mechanisms underlying the increased HIV-1 acquisition rates have not yet been elucidated. Furthermore, it remains unclear if the lack of the vaccine's efficacy reflects a failure of the concept of T cell-mediated protection against HIV-1 or a product failure of the vaccine. Here, we compared two vaccine regimens based on sequential use of AdHu5 vectors or two different chimpanzee-derived Ad vectors in rhesus macaques that were AdHu5 seropositive or seronegative at the onset of vaccination. Our results show that heterologous booster immunizations with the chimpanzee-derived Ad vectors induced higher T and B cell responses than did repeated immunizations with the AdHu5 vector, especially in AdHu5-preexposed macaques.
The Wistar Institute, Philadelphia, PA 19104, USA.
Nia
N
Tatsis
Marcio O
MO
Lasaro
Shih-Wen
SW
Lin
Larissa H
LH
Haut
Zhi Q
ZQ
Xiang
Dongming
D
Zhou
Lauren
L
Dimenna
Hua
H
Li
Ang
A
Bian
Sarah
S
Abdulla
Yan
Y
Li
Wynetta
W
Giles-Davis
Jessica
J
Engram
Sarah J
SJ
Ratcliffe
Guido
G
Silvestri
Hildegund C
HC
Ertl
Michael R
MR
Betts
D016915:AIDS Vaccines / Q000276:immunology*; D000256:Adenoviridae / Q000235:genetics / Q000276:immunology*; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D005822:Genetic Vectors / Q000235:genetics / Q000276:immunology*; D054298:Human Immunodeficiency Virus Proteins / Q000235:genetics / Q000276:immunology*; D007117:Immunization, Secondary / Q000379:methods; D007371:Interferon-gamma / Q000096:biosynthesis; D007376:Interleukin-2 / Q000096:biosynthesis; D008213:Lymphocyte Activation / Q000276:immunology; D008253:Macaca mulatta; D002679:Pan troglodytes; D016133:Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000276:immunology
D016915:AIDS Vaccines; D000914:Antibodies, Viral; D054298:Human Immunodeficiency Virus Proteins; D007376:Interleukin-2; D007371:Interferon-gamma