Natural killer T cell and TLR9 agonists as mucosal adjuvants for sublingual vaccination with clade C HIV-1 envelope protein

Shailbala Singh, Guojun Yang, Siddappa Nagadenahalli Byrareddy, Michael A. Barry, K. Jagannadha Sastry

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

The vast majority of HIV-1 infections occur at mucosa during sexual contact. It may therefore be advantageous to provide mucosal barrier protection against this entry by mucosal vaccination. While a number of mucosal routes of vaccination are possible, many like enteric oral vaccines or intranasal vaccines have significant impediments that limit vaccine efficacy or pose safety risks. In contrast, immunogens applied to the sublingual region of the mouth could provide a simple route for mucosal vaccination. While sublingual immunization is appealing, this site does not always drive strong immune responses, particularly when using protein antigens. To address this issue, we have tested the ability of two mucosal adjuvants: alpha-galactosylceramide (αGalCer) that is a potent stimulator of natural killer T cells and CpG-oligodeoxynucleotide (CpG-ODN) a TLR9 agonist for their ability to amplify immune responses against clade C gp140 HIV-1 envelope protein antigen. Immunization with envelope protein alone resulted in a weak T cell and antibody responses. In contrast, CD4+ and CD8+ T cells responses in systemic and mucosal tissues were significantly higher in mice immunized with gp140 in the presence of either αGalCer or CpG-ODN and these responses were further augmented when the two adjuvants were used together. While both the adjuvants effectively increased gp140-specific serum IgG and vaginal IgA antibody levels, combining both significantly improved these responses. Memory T cell responses 60 days after immunization revealed αGalCer to be more potent than CpG-ODN and the combination of the αGalCer and CpG-ODN adjuvants was more effective than either alone. Serum and vaginal washes collected 60 days after immunization with gp140 with both αGalCer and CpG-ODN adjuvants had significant neutralization activity against Tier 1 and Tier 2 SHIVs. These data support the utility of the sublingual route for mucosal vaccination particularly in combination with αGalCer and CpG-ODN adjuvants.

Original languageEnglish (US)
Pages (from-to)6934-6940
Number of pages7
JournalVaccine
Volume32
Issue number51
DOIs
StatePublished - 2014
Externally publishedYes

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Natural Killer T-Cells
Galactosylceramides
Oligodeoxyribonucleotides
natural killer cells
Human immunodeficiency virus 1
agonists
adjuvants
HIV-1
Vaccination
T-lymphocytes
vaccination
Immunization
immunization
Proteins
Vaccines
proteins
vaccines
antigens
T-Lymphocytes
mouth

Keywords

  • Clade C HIV-1
  • Mucosal adjuvants
  • Mucosal vaccine
  • NKT cell agonist
  • Sublingual
  • TLR9 agonist
  • Vaccine

ASJC Scopus subject areas

  • Immunology and Microbiology(all)
  • Infectious Diseases
  • Public Health, Environmental and Occupational Health
  • veterinary(all)
  • Molecular Medicine
  • Medicine(all)

Cite this

Natural killer T cell and TLR9 agonists as mucosal adjuvants for sublingual vaccination with clade C HIV-1 envelope protein. / Singh, Shailbala; Yang, Guojun; Byrareddy, Siddappa Nagadenahalli; Barry, Michael A.; Sastry, K. Jagannadha.

In: Vaccine, Vol. 32, No. 51, 2014, p. 6934-6940.

Research output: Contribution to journalArticle

Singh, Shailbala ; Yang, Guojun ; Byrareddy, Siddappa Nagadenahalli ; Barry, Michael A. ; Sastry, K. Jagannadha. / Natural killer T cell and TLR9 agonists as mucosal adjuvants for sublingual vaccination with clade C HIV-1 envelope protein. In: Vaccine. 2014 ; Vol. 32, No. 51. pp. 6934-6940.
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