A Novel Adjuvant for Mucosal Immunity to HIV-1 gp120 in Nonhuman Primates

• Published in: The Journal of immunology (1950) 2004-12, Vol.173 (11), p.6850-6857
• Main Authors: Yoshino, Naoto, Lu, Fabien X.-S, Fujihashi, Kohtaro, Hagiwara, Yukari, Kataoka, Kosuke, Lu, Ding, Hirst, Linda, Honda, Mitsuo, van Ginkel, Frederik W, Takeda, Yoshifumi, Miller, Christopher J, Kiyono, Hiroshi, McGhee, Jerry R
• Format: Article
• Language: English
• Subjects: Adjuvants, Immunologic - administration & dosage; Adjuvants, Immunologic - adverse effects; AIDS Vaccines - administration & dosage; AIDS Vaccines - immunology; Animals; Antibody-Producing Cells - immunology; Antibody-Producing Cells - metabolism; Cholera Toxin - administration & dosage; Cholera Toxin - adverse effects; Cholera Toxin - immunology; Epitopes, T-Lymphocyte - immunology; Female; HIV Antibodies - biosynthesis; HIV Antibodies - blood; HIV Envelope Protein gp120 - administration & dosage; HIV Envelope Protein gp120 - immunology; HIV-1 - immunology; Human immunodeficiency virus 1; Immunity, Mucosal; Immunoglobulin A - biosynthesis; Immunoglobulin G - biosynthesis; Lymphoid Tissue - immunology; Lymphoid Tissue - metabolism; Macaca mulatta; Male; Nasal Mucosa - immunology; Nasal Mucosa - metabolism; Neutralization Tests; Primates; Th1 Cells - immunology; Th1 Cells - metabolism; Th2 Cells - immunology; Th2 Cells - metabolism
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.173.11.6850

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.