Tang Neos, Lu Chun-Yi, Sue Shih-Che, Chen Ting-Hsuan, Jan Jia-Tsrong, Huang Ming-Hsi, Huang Chung-Hsiung, Chen Chung-Chu, Chiang Bor-Luen, Huang Li-Min, Wu Suh-Chin
Institute of Biotechnology, National Tsing Hua University, Hsinchu 30013, Taiwan.
Department of Pediatrics, National Taiwan University Children Hospital, Taipei 100226, Taiwan.
Vaccines (Basel). 2020 Nov 30;8(4):710. doi: 10.3390/vaccines8040710.
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 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.
人类感染高致病性禽流感H5N1病毒仍然是全球主要的公共卫生问题。疫苗接种仍然是预防H5N1和其他新型禽流感病毒感染的主要保护策略。我们研究了将IIb型热不稳定肠毒素B亚基（LTIIb-B5）用作黏膜佐剂，与重组HA蛋白联合进行鼻内免疫以预防H5N1禽流感病毒。使用LTIIb-B5佐剂在血清和支气管肺泡灌洗液中引发了更强效的IgG、IgA和中和抗体滴度，从而增强了对致死性病毒攻击的保护作用。发现LTIIb-B5的黏膜佐剂活性可在脾淋巴细胞和颈淋巴结中引发更强的Th17细胞反应。抗IL-17A单克隆抗体耗竭研究和IL-17A基因敲除小鼠研究也表明Th17细胞反应对抗H5N1保护性免疫有贡献。我们的结果表明，使用LTIIb-B5黏膜佐剂与HA亚基蛋白可增强对H5N1活病毒攻击的保护作用，并增加Th17反应，二者之间存在联系。
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