Replication-defective adenovirus serotype 5 vectors elicit durable cellular and humoral immune responses in nonhuman primates.
The magnitude and durability of immune responses induced by replication-defective adenovirus serotype 5 (ADV5) vector-based vaccines were evaluated in the simian-human immunodeficiency virus/rhesus monkey model. A single inoculation of recombinant ADV5 vector constructs induced cellular and humoral immunity, but the rapid generation of neutralizing anti-Ad5 antibodies limited the immunity induced by repeated vector administration. The magnitude and durability of the immune responses elicited by these vaccines were greater when they were delivered as boosting immunogens in plasmid DNA-primed monkeys than when they were used as single-modality immunogens. Therefore, administration of ADV5-based vectors in DNA-primed subjects may be a preferred use of this vaccine modality for generating long-term immune protection.
Santra
Sampa
S
Division of Viral Pathogenesis, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, RE113, P. O. Box 15732, Boston, MA 02215, USA.
Seaman
Michael S
MS
Xu
Ling
L
Barouch
Dan H
DH
Lord
Carol I
CI
Lifton
Michelle A
MA
Gorgone
Darci A
DA
Beaudry
Kristin R
KR
Svehla
Krisha
K
Welcher
Brent
B
Chakrabarti
Bimal K
BK
Huang
Yue
Y
Yang
Zhi-Yong
ZY
Mascola
John R
JR
Nabel
Gary J
GJ
Letvin
Norman L
NL
D016915:AIDS Vaccines / Q000008:administration & dosage / Q000276:immunology; D017498:Adenovirus E1 Proteins / Q000235:genetics; D017503:Adenovirus E3 Proteins / Q000235:genetics; D000260:Adenoviruses, Human / Q000235:genetics / Q000276:immunology*; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood*; D004353:Drug Evaluation, Preclinical; D017353:Gene Deletion; D005822:Genetic Vectors / Q000235:genetics / Q000276:immunology*; D015483:HIV Antibodies / Q000097:blood; D015658:HIV Infections / Q000276:immunology*; D015497:HIV-1 / Q000235:genetics / Q000276:immunology; D007117:Immunization, Secondary; D007273:Injections, Intramuscular; D008253:Macaca mulatta; D009500:Neutralization Tests; D010957:Plasmids / Q000235:genetics; D016097:Simian Acquired Immunodeficiency Syndrome / Q000097:blood / Q000276:immunology*; D015302:Simian Immunodeficiency Virus / Q000235:genetics / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D014611:Vaccination; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000276:immunology; D014765:Viral Vaccines / Q000008:administration & dosage / Q000276:immunology*
D016915:AIDS Vaccines; D017498:Adenovirus E1 Proteins; D017503:Adenovirus E3 Proteins; D000914:Antibodies, Viral; D015483:HIV Antibodies; D019444:Vaccines, DNA; D014765:Viral Vaccines