title: Combination recombinant simian or chimpanzee adenoviral vectors for vaccine development.
abstract: Recombinant adenoviral vector (rAd)-based vaccines are currently being developed for several infectious diseases and cancer therapy, but pre-existing seroprevalence to such vectors may prevent their use in broad human populations. In this study, we investigated the potential of low seroprevalence non-human primate rAd vectors to stimulate cellular and humoral responses using HIV/SIV Env glycoprotein (gp) as the representative antigen. Mice were immunized with novel simian or chimpanzee rAd (rSAV or rChAd) vectors encoding HIV gp or SIV gp by single immunization or in heterologous prime/boost combinations (DNA/rAd; rAd/rAd; rAd/NYVAC or rAd/rLCM), and adaptive immunity was assessed. Among the rSAV and rChAd tested, rSAV16 or rChAd3 vector alone generated the most potent immune responses. The DNA/rSAV regimen also generated immune responses similar to the DNA/rAd5 regimen. rChAd63/rChAd3 and rChAd3 /NYVAC induced similar or even higher levels of CD4+ and CD8+ T-cell and IgG responses as compared to rAd28/rAd5, one of the most potent combinations of human rAds. The optimized vaccine regimen stimulated improved cellular immune responses and neutralizing antibodies against HIV compared to the DNA/rAd5 regimen. Based on these results, this type of novel rAd vector and its prime/boost combination regimens represent promising candidates for vaccine development.
authors.affiliation: Vaccine Research Center, NIAID, National Institutes of Health, Bldg. 40, Room 4502, MSC-3005, 40 Convent Drive, Bethesda, MD 20892-3005, United States. Electronic address: chcheng@mail.nih.gov.
authors.forename: Cheng
authors.initials: C
authors.lastname: Cheng
authors.affiliation: Vaccine Research Center, NIAID, National Institutes of Health, Bldg. 40, Room 4502, MSC-3005, 40 Convent Drive, Bethesda, MD 20892-3005, United States. Electronic address: wangling@niaid.nih.gov.
authors.forename: Lingshu
authors.initials: L
authors.lastname: Wang
authors.affiliation: Vaccine Research Center, NIAID, National Institutes of Health, Bldg. 40, Room 4502, MSC-3005, 40 Convent Drive, Bethesda, MD 20892-3005, United States. Electronic address: kosungyoul@niaid.nih.gov.
authors.forename: Sung-Youl
authors.initials: SY
authors.lastname: Ko
authors.affiliation: Vaccine Research Center, NIAID, National Institutes of Health, Bldg. 40, Room 4502, MSC-3005, 40 Convent Drive, Bethesda, MD 20892-3005, United States. Electronic address: wkong@mail.nih.gov.
authors.forename: Wing-Pui
authors.initials: WP
authors.lastname: Kong
authors.affiliation: Vaccine Research Center, NIAID, National Institutes of Health, Bldg. 40, Room 4502, MSC-3005, 40 Convent Drive, Bethesda, MD 20892-3005, United States. Electronic address: schmidtst@niaid.nih.gov.
authors.forename: Stephen D
authors.initials: SD
authors.lastname: Schmidt
authors.affiliation: GenVec, Inc., 65 West Watkins Mill Rd., Gaithersburg, MD 20878, United States. Electronic address: jason.gall@nih.gov.
authors.forename: Jason G D
authors.initials: JGD
authors.lastname: Gall
authors.affiliation: Okairos Srl, Viale Città d'Europa 679, 00144, Rome, Italy. Electronic address: stefano.colloca@reithera.com.
authors.forename: Stefano
authors.initials: S
authors.lastname: Colloca
authors.affiliation: Vaccine Research Center, NIAID, National Institutes of Health, Bldg. 40, Room 4502, MSC-3005, 40 Convent Drive, Bethesda, MD 20892-3005, United States. Electronic address: rseder@mail.nih.gov.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Seder
authors.affiliation: Vaccine Research Center, NIAID, National Institutes of Health, Bldg. 40, Room 4502, MSC-3005, 40 Convent Drive, Bethesda, MD 20892-3005, United States. Electronic address: jmascola@mail.nih.gov.
authors.forename: John R
authors.initials: JR
authors.lastname: Mascola
authors.affiliation: Vaccine Research Center, NIAID, National Institutes of Health, Bldg. 40, Room 4502, MSC-3005, 40 Convent Drive, Bethesda, MD 20892-3005, United States. Electronic address: Gary.Nabel@sanofi.com.
authors.forename: Gary J
authors.initials: GJ
authors.lastname: Nabel
mesh_terms: D016915:AIDS Vaccines / Q000235:genetics / Q000276:immunology / Q000302:isolation & purification; D000261:Adenoviruses, Simian / Q000235:genetics* / Q000276:immunology*; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D004337:Drug Carriers; D055808:Drug Discovery / Q000379:methods*; D005260:Female; D005822:Genetic Vectors; D007074:Immunoglobulin G / Q000097:blood; D008807:Mice, Inbred BALB C; D018449:SAIDS Vaccines / Q000235:genetics / Q000276:immunology / Q000302:isolation & purification; D019444:Vaccines, DNA / Q000235:genetics / Q000276:immunology / Q000302:isolation & purification; D014614:Vaccines, Synthetic / Q000235:genetics / Q000276:immunology / Q000302:isolation & purification; D014765:Viral Vaccines / Q000235:genetics / Q000276:immunology* / Q000302:isolation & purification*
chemical_list: D016915:AIDS Vaccines; D000914:Antibodies, Viral; D004337:Drug Carriers; D007074:Immunoglobulin G; D018449:SAIDS Vaccines; D019444:Vaccines, DNA; D014614:Vaccines, Synthetic; D014765:Viral Vaccines
keywords: Adenoviral vectors; Cellular immune response; Chimpanzee adenovirus; Humoral immune response; Simian adenovirus; Vaccine development