Nasal immunization of nonhuman primates with simian immunodeficiency virus p55gag and cholera toxin adjuvant induces Th1/Th2 help for virus-specific immune responses in reproductive tissues.
Female rhesus macaques were nasally immunized with p55gag (p55) of SIV and cholera toxin as a mucosal adjuvant. Nasal immunization induced Ag-specific IgA and IgG Abs in mucosal secretions (e.g., cervicovaginal secretions, rectal washes, and saliva) and serum. Furthermore, high numbers of p55-specific IgA and IgG Ab-forming cells were induced in mucosal effector sites, i.e., uterine cervix, intestinal lamina propria, and nasal passage. p55-specific CD4+ T cells in both systemic and mucosal compartments expressed IFN-gamma and IL-2 (Th1-type)- as well as IL-5, IL-6, and IL-10 (Th2-type)-specific mRNA. Moreover, p55-specific CTL activity was demonstrated in lymphocytes from blood, tonsils, and other lymphoid tissues. These results show that nasal immunization with SIV p55 with cholera toxin elicits both Th1- and selective Th2-type cytokine responses associated with the induction of SIV-specific mucosal and serum Abs, and CTL activity. These results offer a promise for the development of protective mucosal immunity to SIV.
Imaoka
K
K
Immunobiology Vaccine Center, Department of Oral Biology, University of Alabama, Birmingham 35294, USA.
Miller
C J
CJ
Kubota
M
M
McChesney
M B
MB
Lohman
B
B
Yamamoto
M
M
Fujihashi
K
K
Someya
K
K
Honda
M
M
McGhee
J R
JR
Kiyono
H
H
D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000818:Animals; D000914:Antibodies, Viral / Q000096:biosynthesis*; D000921:Antibody-Producing Cells / Q000276:immunology; D000956:Antigens, Viral / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D002772:Cholera Toxin / Q000276:immunology*; D016207:Cytokines / Q000096:biosynthesis; D003602:Cytotoxicity, Immunologic; D005260:Female; D015683:Gene Products, gag / Q000276:immunology*; D008253:Macaca mulatta; D009297:Nasal Mucosa / Q000166:cytology / Q000276:immunology*; D015302:Simian Immunodeficiency Virus / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology* / Q000378:metabolism; D018418:Th2 Cells / Q000276:immunology* / Q000378:metabolism; D014621:Vagina / Q000276:immunology* / Q000378:metabolism
D000276:Adjuvants, Immunologic; D000914:Antibodies, Viral; D000956:Antigens, Viral; D016207:Cytokines; D015683:Gene Products, gag; C115853:simian immunodeficiency virus gag p55; D002772:Cholera Toxin