title: Enhancement of Mucosal Immunogenicity of Viral Vectored Vaccines by the NKT Cell Agonist Alpha-Galactosylceramide as Adjuvant.
abstract: Gene-based vaccination strategies, specifically viral vectors encoding vaccine immunogens are effective at priming strong immune responses. Mucosal routes offer practical advantages for vaccination by ease of needle-free administration, and immunogen delivery at readily accessible oral/nasal sites to efficiently induce immunity at distant gut and genital tissues. However, since mucosal tissues are inherently tolerant for induction of immune responses, incorporation of adjuvants for optimal mucosal vaccination strategies is important. We report here the effectiveness of alpha-galactosylceramide (α-GalCer), a synthetic glycolipid agonist of natural killer T (NKT) cells, as an adjuvant for enhancing immunogenicity of vaccine antigens delivered using viral vectors by mucosal routes in murine and nonhuman primate models. Significant improvement in adaptive immune responses in systemic and mucosal tissues was observed by including α-GalCer adjuvant for intranasal immunization of mice with vesicular stomatitis virus vector encoding the model antigen ovalbumin and adenoviral vectors expressing HIV env and Gag antigens. Activation of NKT cells in systemic and mucosal tissues along with significant increases in adaptive immune responses were observed in rhesus macaques immunized by intranasal and sublingual routes with protein or adenovirus vectored antigens when combined with α-GalCer adjuvant. These results support the utility of α-GalCer adjuvant for enhancing immunogenicity of mucosal vaccines delivered using viral vectors.
authors.affiliation: Department of Immunology, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Shailbala
authors.initials: S
authors.lastname: Singh
authors.affiliation: Department of Veterinary Sciences, The University of Texas M.D. Anderson Cancer Center, Bastrop, TX 78602, USA.
authors.forename: Pramod N
authors.initials: PN
authors.lastname: Nehete
authors.affiliation: Department of Immunology, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Guojun
authors.initials: G
authors.lastname: Yang
authors.affiliation: Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Hong
authors.initials: H
authors.lastname: He
authors.affiliation: Department of Veterinary Sciences, The University of Texas M.D. Anderson Cancer Center, Bastrop, TX 78602, USA.
authors.forename: Bharti
authors.initials: B
authors.lastname: Nehete
authors.affiliation: Rocky Mountain Veterinary Branch, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health Rocky Mountain Laboratories, Hamilton, MT 59840, USA.
authors.forename: Patrick W
authors.initials: PW
authors.lastname: Hanley
authors.affiliation: Department of Internal Medicine, Division of Infectious Diseases, Mayo Clinic, Rochester, MN 55902, USA ; Department of Molecular Medicine, Mayo Clinic, Rochester, MN 55902, USA ; Department of Immunology, Mayo Clinic, Rochester, MN 55902, USA ; Translational Immunovirology and Biodefense Program, Mayo Clinic, Rochester, MN 55902, USA.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Barry
authors.affiliation: Department of Immunology, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA ; Department of Veterinary Sciences, The University of Texas M.D. Anderson Cancer Center, Bastrop, TX 78602, USA.
authors.forename: K Jagannadha
authors.initials: KJ
authors.lastname: Sastry
keywords: HIV vaccine; NKT cells; Rhesus macaques; adenovirus vector; alpha-galactosylceramide; intranasal; mucosal immunity; vesicular stomatitis viral vector