Type IIb Heat Labile Enterotoxin B Subunit as a Mucosal Adjuvant to Enhance Protective Immunity against H5N1 Avian Influenza Viruses
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 <i>E. coli</i> type IIb heat labile...
| Main Authors: | , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2020-11-01
|
| Series: | Vaccines |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2076-393X/8/4/710 |
| _version_ | 1797546140144500736 |
|---|---|
| author | Neos Tang Chun-Yi Lu Shih-Che Sue Ting-Hsuan Chen Jia-Tsrong Jan Ming-Hsi Huang Chung-Hsiung Huang Chung-Chu Chen Bor-Luen Chiang Li-Min Huang Suh-Chin Wu |
| author_facet | Neos Tang Chun-Yi Lu Shih-Che Sue Ting-Hsuan Chen Jia-Tsrong Jan Ming-Hsi Huang Chung-Hsiung Huang Chung-Chu Chen Bor-Luen Chiang Li-Min Huang Suh-Chin Wu |
| author_sort | Neos Tang |
| collection | DOAJ |
| description | 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 <i>E. coli</i> 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. |
| first_indexed | 2024-03-10T14:24:53Z |
| format | Article |
| id | doaj.art-0a416adb4e1b44dfaeb6dac3586ba5e5 |
| institution | Directory Open Access Journal |
| issn | 2076-393X |
| language | English |
| last_indexed | 2024-03-10T14:24:53Z |
| publishDate | 2020-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Vaccines |
| spelling | doaj.art-0a416adb4e1b44dfaeb6dac3586ba5e52023-11-20T23:01:13ZengMDPI AGVaccines2076-393X2020-11-018471010.3390/vaccines8040710Type IIb Heat Labile Enterotoxin B Subunit as a Mucosal Adjuvant to Enhance Protective Immunity against H5N1 Avian Influenza VirusesNeos Tang0Chun-Yi Lu1Shih-Che Sue2Ting-Hsuan Chen3Jia-Tsrong Jan4Ming-Hsi Huang5Chung-Hsiung Huang6Chung-Chu Chen7Bor-Luen Chiang8Li-Min Huang9Suh-Chin Wu10Institute of Biotechnology, National Tsing Hua University, Hsinchu 30013, TaiwanDepartment of Pediatrics, National Taiwan University Children Hospital, Taipei 100226, TaiwanDepartment of Life Science, Institute of Bioinformatics and Structural Biology, National Tsing Hua University, Hsinchu 30013, TaiwanInstitute of Biotechnology, National Tsing Hua University, Hsinchu 30013, TaiwanGenomics Research Center, Academia Sinica, Taipei 11529, TaiwanNational Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Zhunan 35053, TaiwanDepartment of Food Science, National Taiwan Ocean University, Keelung 202301, TaiwanDepartment of Internal Medicine, MacKay Memorial Hospital, Hsinchu 30013, TaiwanDepartment of Pediatrics, National Taiwan University Children Hospital, Taipei 100226, TaiwanDepartment of Pediatrics, National Taiwan University Children Hospital, Taipei 100226, TaiwanInstitute of Biotechnology, National Tsing Hua University, Hsinchu 30013, TaiwanHuman 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 <i>E. coli</i> 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.https://www.mdpi.com/2076-393X/8/4/710intranasal immunizationmucosal adjuvantLTIIb-B5H5N1 vaccine |
| spellingShingle | Neos Tang Chun-Yi Lu Shih-Che Sue Ting-Hsuan Chen Jia-Tsrong Jan Ming-Hsi Huang Chung-Hsiung Huang Chung-Chu Chen Bor-Luen Chiang Li-Min Huang Suh-Chin Wu Type IIb Heat Labile Enterotoxin B Subunit as a Mucosal Adjuvant to Enhance Protective Immunity against H5N1 Avian Influenza Viruses Vaccines intranasal immunization mucosal adjuvant LTIIb-B5 H5N1 vaccine |
| title | Type IIb Heat Labile Enterotoxin B Subunit as a Mucosal Adjuvant to Enhance Protective Immunity against H5N1 Avian Influenza Viruses |
| title_full | Type IIb Heat Labile Enterotoxin B Subunit as a Mucosal Adjuvant to Enhance Protective Immunity against H5N1 Avian Influenza Viruses |
| title_fullStr | Type IIb Heat Labile Enterotoxin B Subunit as a Mucosal Adjuvant to Enhance Protective Immunity against H5N1 Avian Influenza Viruses |
| title_full_unstemmed | Type IIb Heat Labile Enterotoxin B Subunit as a Mucosal Adjuvant to Enhance Protective Immunity against H5N1 Avian Influenza Viruses |
| title_short | Type IIb Heat Labile Enterotoxin B Subunit as a Mucosal Adjuvant to Enhance Protective Immunity against H5N1 Avian Influenza Viruses |
| title_sort | type iib heat labile enterotoxin b subunit as a mucosal adjuvant to enhance protective immunity against h5n1 avian influenza viruses |
| topic | intranasal immunization mucosal adjuvant LTIIb-B5 H5N1 vaccine |
| url | https://www.mdpi.com/2076-393X/8/4/710 |
| work_keys_str_mv | AT neostang typeiibheatlabileenterotoxinbsubunitasamucosaladjuvanttoenhanceprotectiveimmunityagainsth5n1avianinfluenzaviruses AT chunyilu typeiibheatlabileenterotoxinbsubunitasamucosaladjuvanttoenhanceprotectiveimmunityagainsth5n1avianinfluenzaviruses AT shihchesue typeiibheatlabileenterotoxinbsubunitasamucosaladjuvanttoenhanceprotectiveimmunityagainsth5n1avianinfluenzaviruses AT tinghsuanchen typeiibheatlabileenterotoxinbsubunitasamucosaladjuvanttoenhanceprotectiveimmunityagainsth5n1avianinfluenzaviruses AT jiatsrongjan typeiibheatlabileenterotoxinbsubunitasamucosaladjuvanttoenhanceprotectiveimmunityagainsth5n1avianinfluenzaviruses AT minghsihuang typeiibheatlabileenterotoxinbsubunitasamucosaladjuvanttoenhanceprotectiveimmunityagainsth5n1avianinfluenzaviruses AT chunghsiunghuang typeiibheatlabileenterotoxinbsubunitasamucosaladjuvanttoenhanceprotectiveimmunityagainsth5n1avianinfluenzaviruses AT chungchuchen typeiibheatlabileenterotoxinbsubunitasamucosaladjuvanttoenhanceprotectiveimmunityagainsth5n1avianinfluenzaviruses AT borluenchiang typeiibheatlabileenterotoxinbsubunitasamucosaladjuvanttoenhanceprotectiveimmunityagainsth5n1avianinfluenzaviruses AT liminhuang typeiibheatlabileenterotoxinbsubunitasamucosaladjuvanttoenhanceprotectiveimmunityagainsth5n1avianinfluenzaviruses AT suhchinwu typeiibheatlabileenterotoxinbsubunitasamucosaladjuvanttoenhanceprotectiveimmunityagainsth5n1avianinfluenzaviruses |