Oral immunization with simian immunodeficiency virus p55gag and cholera toxin elicits both mucosal IgA and systemic IgG immune responses in nonhuman primates

Mitsuru Kubota, Chris J Miller, Koichi Imaoka, Shigetada Kawabata, Kohtaro Fujihashi, Jerry R. McGhee, Hiroshi Kiyono

Research output: Contribution to journalArticle

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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 languageEnglish (US)
Pages (from-to)5321-5329
Number of pages9
JournalJournal of Immunology
Volume158
Issue number11
StatePublished - 1997

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Simian Immunodeficiency Virus
Cholera Toxin
Interleukin-4
Interleukin-10
Immunoglobulin A
Primates
Immunization
Immunoglobulin G
Macaca
Cytokines
T-Lymphocytes
Interleukin-6
Macaca mulatta
Reverse Transcriptase Polymerase Chain Reaction
Vaccines
Messenger RNA

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 journalArticle

Kubota, Mitsuru ; Miller, Chris J ; Imaoka, Koichi ; Kawabata, Shigetada ; Fujihashi, Kohtaro ; McGhee, Jerry R. ; Kiyono, Hiroshi. / Oral immunization with simian immunodeficiency virus p55gag and cholera toxin elicits both mucosal IgA and systemic IgG immune responses in nonhuman primates. In: Journal of Immunology. 1997 ; Vol. 158, No. 11. pp. 5321-5329.
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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

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AU - Fujihashi, Kohtaro

AU - McGhee, Jerry R.

AU - Kiyono, Hiroshi

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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.

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