Type iib heat labile enterotoxin b subunit as a mucosal adjuvant to enhance protective immunity against h5n1 avian influenza viruses
Journal
Vaccines
Journal Volume
8
Journal Issue
4
Pages
1-17
Date Issued
2020
Author(s)
Tang N.
Sue S.-C.
Chen T.-H.
Jan J.-T.
Huang M.-H.
Huang C.-H.
Chen C.-C.
Wu S.-C.
Abstract
Human infections with highly pathogenic avian influenza H5N1 viruses persist as a major global health concern. Vaccination remains the primary protective strategy against H5N1 and other novel avian influenza virus infections. We investigated the use of E. coli type IIb heat labile enterotoxin B subunit (LTIIb-B5) as a mucosal adjuvant for intranasal immunizations with recombinant HA proteins against H5N1 avian influenza viruses. Use of LTIIb-B5 adjuvant elicited more potent IgG, IgA, and neutralizing antibody titers in both sera and bronchoalveolar lavage fluids, thus increasing protection against lethal virus challenges. LTIIb-B5 mucosal adjuvanticity was found to trigger stronger Th17 cellular response in spleen lymphocytes and cervical lymph nodes. Studies of anti-IL-17A monoclonal antibody depletion and IL-17A knockout mice also suggest the contribution from Th17 cellular response to anti-H5N1 protective immunity. Our results indicate a link between improved protection against H5N1 live virus challenges and increased Th17 response due to the use of LTIIb-B5 mucosal adjuvant with HA subunit proteins. ? 2020 by the authors. Licensee MDPI, Basel, Switzerland.
SDGs
Other Subjects
enterotoxin; gamma interferon; immunoglobulin A; immunoglobulin G; interleukin 17; interleukin 1beta; interleukin 4; interleukin 6; monoclonal antibody; neutralizing antibody; tumor necrosis factor; adjuvant therapy; animal cell; animal experiment; animal model; animal tissue; Article; avian influenza (H5N1); bronchoalveolar lavage fluid; CD4+ T lymphocyte; cellular immunity; centrifugation; cervical lymph node; cloning; controlled study; cytokine production; enzyme linked immunosorbent assay; female; flow cytometry; genetic transfection; HEK293T cell line; heterologous immunity; histopathology; humoral immunity; IC50; ID50; immune response; immunity; immunization; immunoblotting; innate immunity; LD50; lung lavage; MDCK cell line; mouse; nonhuman; optical density; polyacrylamide gel electrophoresis; protein expression; protein purification; spleen lymphocyte; Th17 cell; tumor immunity; vaccination; virus load; virus neutralization
Publisher
MDPI AG
Type
journal article