A novel adjuvant for mucosal immunity to HIV-1 gp120 in nonhuman primates.
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.
Yoshino
Naoto
N
Department of Oral Biology and Microbiology, Immunobiology Vaccine Center, University of Alabama, Birmingham, AL 35294, USA.
Lü
Fabien X-S
FX
Fujihashi
Kohtaro
K
Hagiwara
Yukari
Y
Kataoka
Kosuke
K
Lu
Ding
D
Hirst
Linda
L
Honda
Mitsuo
M
van Ginkel
Frederik W
FW
Takeda
Yoshifumi
Y
Miller
Christopher J
CJ
Kiyono
Hiroshi
H
McGhee
Jerry R
JR
D016915:AIDS Vaccines / Q000008:administration & dosage* / Q000276:immunology; D000276:Adjuvants, Immunologic / Q000008:administration & dosage* / Q000009:adverse effects; D000818:Animals; D000921:Antibody-Producing Cells / Q000276:immunology / Q000378:metabolism; D002772:Cholera Toxin / Q000008:administration & dosage* / Q000009:adverse effects / Q000276:immunology; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D005260:Female; D015483:HIV Antibodies / Q000096:biosynthesis / Q000097:blood; D015699:HIV Envelope Protein gp120 / Q000008:administration & dosage* / Q000276:immunology; D015497:HIV-1 / Q000276:immunology*; D018928:Immunity, Mucosal; D007070:Immunoglobulin A / Q000096:biosynthesis; D007074:Immunoglobulin G / Q000096:biosynthesis; D008221:Lymphoid Tissue / Q000276:immunology / Q000378:metabolism; D008253:Macaca mulatta; D008297:Male; D009297:Nasal Mucosa / Q000276:immunology* / Q000378:metabolism; D009500:Neutralization Tests; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism
D016915:AIDS Vaccines; D000276:Adjuvants, Immunologic; D018984:Epitopes, T-Lymphocyte; D015483:HIV Antibodies; D015699:HIV Envelope Protein gp120; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D002772:Cholera Toxin