Immunogenicity of attenuated vesicular stomatitis virus vectors expressing HIV type 1 Env and SIV Gag proteins: comparison of intranasal and intramuscular vaccination routes.
An experimental AIDS vaccine based on attenuated, recombinant vesicular stomatitis virus (rVSV), when administered by a combination of parenteral and mucosal routes, has proven effective at preventing AIDS in a rhesus macaque model (Rose NF, et al.: Cell 2001;106:539-549). In an effort to determine the optimal route of vaccine administration we evaluated the ability of rVSV-based vaccine vectors expressing HIV-1 Env and SIV Gag proteins, when given either intramuscularly (i.m.) or intranasally (i.n.), to elicit antigen-specific cellular and humoral immune responses, and to protect from a subsequent vaginal challenge with simian-human immunodeficiency virus (SHIV89.6P). Our results demonstrate that macaques vaccinated by the i.n. route developed significantly higher antigen-specific cellular immune responses as determined by MHC class I tetramer staining, IFN-gamma ELISPOT, and cytotoxic T cell assays. However, systemic and mucosal humoral immune responses did not vary significantly with the route of vaccine administration. Given the importance of cell-mediated immune responses in slowing AIDS progression, intranasal delivery of a VSV-based AIDS vaccine may be an optimal as well as practical route for vaccination and should be considered in design of clinical trials.
Egan
Michael A
MA
Wyeth Vaccines Research, Pearl River, New York 10965, USA. eganm@wyeth.com
Chong
Siew Yen
SY
Rose
Nina F
NF
Megati
Shakuntala
S
Lopez
Kevin J
KJ
Schadeck
Eva B
EB
Johnson
J Erik
JE
Masood
Amjed
A
Piacente
Priscilla
P
Druilhet
Robert E
RE
Barras
Paul W
PW
Hasselschwert
Dana L
DL
Reilly
Patricia
P
Mishkin
Eric M
EM
Montefiori
David C
DC
Lewis
Mark G
MG
Clarke
David K
DK
Hendry
R Michael
RM
Marx
Preston A
PA
Eldridge
John H
JH
Udem
Stephen A
SA
Israel
Zimra R
ZR
Rose
John K
JK
D016915:AIDS Vaccines / Q000008:administration & dosage / Q000276:immunology*; D000281:Administration, Intranasal; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D005260:Female; D015686:Gene Products, env / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D015683:Gene Products, gag / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D005822:Genetic Vectors / Q000008:administration & dosage / Q000276:immunology*; D015483:HIV Antibodies / Q000097:blood; D015658:HIV Infections / Q000276:immunology / Q000517:prevention & control; D015497:HIV-1 / Q000276:immunology; D006801:Humans; D007273:Injections, Intramuscular; D007371:Interferon-gamma / Q000096:biosynthesis; D008253:Macaca mulatta; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology / Q000517:prevention & control; D015302:Simian Immunodeficiency Virus / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology; D014611:Vaccination; D014613:Vaccines, Attenuated / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D014721:Vesicular stomatitis Indiana virus / Q000235:genetics / Q000276:immunology*
D016915:AIDS Vaccines; D000914:Antibodies, Viral; D015686:Gene Products, env; D015683:Gene Products, gag; D015483:HIV Antibodies; D014613:Vaccines, Attenuated; D007371:Interferon-gamma