Enhancement of mucosal immunogenicity of viral vectored vaccines by the NKT cell agonist alpha-galactosylceramide as adjuvant

Shailbala Singh, Pramod N. Nehete, Guojun Yang, Hong He, Bharti Nehete, Patrick W. Hanley, Michael A. Barry, K. Jagannadha Sastry

Research output: Contribution to journalArticle

7 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)686-706
Number of pages21
JournalVaccines
Volume2
Issue number4
DOIs
StatePublished - Oct 24 2014

Keywords

  • Adenovirus vector
  • Alpha-galactosylceramide
  • HIV vaccine
  • Intranasal
  • Mucosal immunity
  • NKT cells
  • Rhesus macaques
  • Vesicular stomatitis viral vector

ASJC Scopus subject areas

  • Immunology
  • Pharmacology
  • Drug Discovery
  • Infectious Diseases
  • Pharmacology (medical)

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