title: Immunogenicity of attenuated vesicular stomatitis virus vectors expressing HIV type 1 Env and SIV Gag proteins: comparison of intranasal and intramuscular vaccination routes.
abstract: 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.
authors.affiliation: Wyeth Vaccines Research, Pearl River, New York 10965, USA. eganm@wyeth.com
authors.forename: Michael A
authors.initials: MA
authors.lastname: Egan
authors.forename: Siew Yen
authors.initials: SY
authors.lastname: Chong
authors.forename: Nina F
authors.initials: NF
authors.lastname: Rose
authors.forename: Shakuntala
authors.initials: S
authors.lastname: Megati
authors.forename: Kevin J
authors.initials: KJ
authors.lastname: Lopez
authors.forename: Eva B
authors.initials: EB
authors.lastname: Schadeck
authors.forename: J Erik
authors.initials: JE
authors.lastname: Johnson
authors.forename: Amjed
authors.initials: A
authors.lastname: Masood
authors.forename: Priscilla
authors.initials: P
authors.lastname: Piacente
authors.forename: Robert E
authors.initials: RE
authors.lastname: Druilhet
authors.forename: Paul W
authors.initials: PW
authors.lastname: Barras
authors.forename: Dana L
authors.initials: DL
authors.lastname: Hasselschwert
authors.forename: Patricia
authors.initials: P
authors.lastname: Reilly
authors.forename: Eric M
authors.initials: EM
authors.lastname: Mishkin
authors.forename: David C
authors.initials: DC
authors.lastname: Montefiori
authors.forename: Mark G
authors.initials: MG
authors.lastname: Lewis
authors.forename: David K
authors.initials: DK
authors.lastname: Clarke
authors.forename: R Michael
authors.initials: RM
authors.lastname: Hendry
authors.forename: Preston A
authors.initials: PA
authors.lastname: Marx
authors.forename: John H
authors.initials: JH
authors.lastname: Eldridge
authors.forename: Stephen A
authors.initials: SA
authors.lastname: Udem
authors.forename: Zimra R
authors.initials: ZR
authors.lastname: Israel
authors.forename: John K
authors.initials: JK
authors.lastname: Rose
mesh_terms: 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*
chemical_list: D016915:AIDS Vaccines; D000914:Antibodies, Viral; D015686:Gene Products, env; D015683:Gene Products, gag; D015483:HIV Antibodies; D014613:Vaccines, Attenuated; D007371:Interferon-gamma