Abstract
Rhesus macaques were orally immunized with a mucosal vaccine consisting of two different concentrations (1 mg vs 250 μg) of recombinant SIV p55gag (p55) with or without cholera toxin (CT, 50 μg) 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 μg) 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-γ) and Th2 (IL-4 and IL-10) cytokines, both IFN-γ and IL-10 were present, but IL-4 was absent. CD4+ T cells isolated from these p55-stimulated PBMCs contained IFN-γ 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-γ, IL-6, and IL-10, but not IL-4. These findings suggest that oral immunization of nonhuman primates induced both IFN-γ-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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 5321-5329 |
| Number of pages | 9 |
| Journal | Journal of Immunology |
| Volume | 158 |
| Issue number | 11 |
| State | Published - 1997 |
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ASJC Scopus subject areas
- Immunology
Cite this
Oral immunization with simian immunodeficiency virus p55gag and cholera toxin elicits both mucosal IgA and systemic IgG immune responses in nonhuman primates. / Kubota, Mitsuru; Miller, Chris J; Imaoka, Koichi; Kawabata, Shigetada; Fujihashi, Kohtaro; McGhee, Jerry R.; Kiyono, Hiroshi.
In: Journal of Immunology, Vol. 158, No. 11, 1997, p. 5321-5329.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Oral immunization with simian immunodeficiency virus p55gag and cholera toxin elicits both mucosal IgA and systemic IgG immune responses in nonhuman primates
AU - Kubota, Mitsuru
AU - Miller, Chris J
AU - Imaoka, Koichi
AU - Kawabata, Shigetada
AU - Fujihashi, Kohtaro
AU - McGhee, Jerry R.
AU - Kiyono, Hiroshi
PY - 1997
Y1 - 1997
N2 - Rhesus macaques were orally immunized with a mucosal vaccine consisting of two different concentrations (1 mg vs 250 μg) of recombinant SIV p55gag (p55) with or without cholera toxin (CT, 50 μg) 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 μg) 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-γ) and Th2 (IL-4 and IL-10) cytokines, both IFN-γ and IL-10 were present, but IL-4 was absent. CD4+ T cells isolated from these p55-stimulated PBMCs contained IFN-γ 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-γ, IL-6, and IL-10, but not IL-4. These findings suggest that oral immunization of nonhuman primates induced both IFN-γ-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.
AB - Rhesus macaques were orally immunized with a mucosal vaccine consisting of two different concentrations (1 mg vs 250 μg) of recombinant SIV p55gag (p55) with or without cholera toxin (CT, 50 μg) 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 μg) 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-γ) and Th2 (IL-4 and IL-10) cytokines, both IFN-γ and IL-10 were present, but IL-4 was absent. CD4+ T cells isolated from these p55-stimulated PBMCs contained IFN-γ 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-γ, IL-6, and IL-10, but not IL-4. These findings suggest that oral immunization of nonhuman primates induced both IFN-γ-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.
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UR - http://www.scopus.com/inward/citedby.url?scp=0031159818&partnerID=8YFLogxK
M3 - Article
C2 - 9164952
AN - SCOPUS:0031159818
VL - 158
SP - 5321
EP - 5329
JO - Journal of Immunology
JF - Journal of Immunology
SN - 0022-1767
IS - 11
ER -