Oral immunization with simian immunodeficiency virus p55gag and cholera toxin elicits both mucosal IgA and systemic IgG immune responses in nonhuman primates.
Rhesus macaques were orally immunized with a mucosal vaccine consisting of two different concentrations (1 mg vs 250 microg) of recombinant SIV p55gag (p55) with or without cholera toxin (CT, 50 microg) as a mucosal adjuvant. The plasma from macaques receiving the higher dose of p55 (1 mg) and CT had higher p55-specific IgG and IgA Ab titers compared with macaques that received the lower dose of p55 (250 microg) and CT. Further, high levels of p55-specific IgG and IgA Abs were present in external secretions from both groups. The level of p55-induced T cell responses was elevated in PBMCs isolated from the high dose group compared with the low dose group. When culture supernatants from these p55-stimulated PBMCs were examined for Th1 (IFN-gamma) and Th2 (IL-4 and IL-10) cytokines, both IFN-gamma and IL-10 were present, but IL-4 was absent. CD4+ T cells isolated from these p55-stimulated PBMCs contained IFN-gamma spot-forming cells (SFCs) but not IL-4 SFCs. These results were further confirmed by cytokine-specific reverse transcriptase PCR analysis, where p55-specific CD4+ T cells expressed mRNA for IFN-gamma, IL-6, and IL-10, but not IL-4. These findings suggest that oral immunization of nonhuman primates induced both IFN-gamma-secreting Th1 and select Th2 cytokine (e.g., IL-6 and IL-10)-producing CD4+ Th cells, which accounted for the generation of p55-specific systemic and mucosal Ab responses.
Kubota
M
M
The Immunobiology Vaccine Center, Department of Oral Biology, University of Alabama at Birmingham Medical Center, 35294, USA.
Miller
C J
CJ
Imaoka
K
K
Kawabata
S
S
Fujihashi
K
K
McGhee
J R
JR
Kiyono
H
H
D000284:Administration, Oral; D000818:Animals; D002772:Cholera Toxin / Q000008:administration & dosage / Q000276:immunology*; D015683:Gene Products, gag / Q000008:administration & dosage / Q000276:immunology*; D007109:Immunity; D018928:Immunity, Mucosal; D007114:Immunization; D007070:Immunoglobulin A / Q000096:biosynthesis* / Q000276:immunology; D007074:Immunoglobulin G / Q000096:biosynthesis* / Q000276:immunology; D008253:Macaca mulatta; D011498:Protein Precursors / Q000008:administration & dosage / Q000276:immunology*; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000276:immunology; D015302:Simian Immunodeficiency Virus / Q000276:immunology*
D015683:Gene Products, gag; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D011498:Protein Precursors; D011994:Recombinant Proteins; C059767:p55 gag precursor protein, Human immunodeficiency virus 1; D002772:Cholera Toxin