A novel adjuvant for mucosal immunity to HIV-1 gp120 in nonhuman primates

Naoto Yoshino, Fabien X S Lü, Kohtaro Fujihashi, Yukari Hagiwara, Kosuke Kataoka, Ding Lu, Linda Hirst, Mitsuo Honda, Frederik W. Van Ginkel, Yoshifumi Takeda, Chris J Miller, Hiroshi Kiyono, Jerry R. McGhee

Research output: Contribution to journalArticle

29 Scopus citations

Abstract

The development of a safe and effective mucosal adjuvant is a crucial step toward a mucosal HIV/AIDS vaccine. This study seeks to determine the promise of a nontoxic mutant of cholera toxin (mCT; E112K) as a mucosal adjuvant in nonhuman primates. HIV-1 gp120 was nasally administered together with mCT E112K or native CT (nCT) as adjuvant on five to six occasions over a 6- to 8-wk period to groups of four rhesus macaques and alone to two monkeys that acted as controls. Macaques given nasal gp120 with either mCT E112K or nCT showed elevated gp120-specific IgG and IgA Ab responses with virus-neutralizing activity in both their plasma and mucosal external secretions, as well as higher numbers of gp120-specific IgA Ab-forming cells in their mucosal and peripheral lymphoid tissues and of IL-4-producing Th2-type CD4-positive (CD4+) T cells than did controls. Even though significant mucosal adjuvanticity was seen with both mCT E112K and nCT, neuronal damage was observed only in the nCT-treated, but not in the control or mCT E112K-treated groups. These results clearly show that mCT E112K is an effective and safe mucosal adjuvant for the development of a nasal HIV/AIDS vaccine.

Original languageEnglish (US)
Pages (from-to)6850-6857
Number of pages8
JournalJournal of Immunology
Volume173
Issue number11
StatePublished - Dec 1 2004

ASJC Scopus subject areas

  • Immunology

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    Yoshino, N., Lü, F. X. S., Fujihashi, K., Hagiwara, Y., Kataoka, K., Lu, D., Hirst, L., Honda, M., Van Ginkel, F. W., Takeda, Y., Miller, C. J., Kiyono, H., & McGhee, J. R. (2004). A novel adjuvant for mucosal immunity to HIV-1 gp120 in nonhuman primates. Journal of Immunology, 173(11), 6850-6857.