Relationship between coxackievirus A16 antigen and innate lymphoid cells in respiratory tract epithelia and immunological analysis of its vaccine development
WANG Yongrong1, LIAN Yaru1,2, JIANG Guorun1, FAN Shengtao1, FENG Min1, YANG Erxia2, JIANG Li2, DONG Chenghong2, ZHAO Zhimei1, WANG Lichun1, LIAO Yun1, ZHANG Ying1, LI Qihan1
1. Institute of Medical Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Yunnan Key Laboratory of Vaccine Research and Development on Severe Infectious Diseases, Kunming 650118, China; 2. Jiangsu Convac Biotechnology Co., Ltd., Taizhou 225300, China
Abstract：Coxackievirus A16 (CA16) is a major pathogen of hand, foot and mouth disease. Because of the unclear pathogenesis and immunomechanism of CA16, the development of a CA16 vaccine has encountered numerous difficulties. Many studies have reported that epithelial cells and associated immune cells in respiratory tract mucosa, especially innate lymphoid cells (ILCs), are largely contributed to the activation of innate and adaptive immune responses during viral infection. It is still unknown that whether ILCs play a similar role in the immune response induced by CA16 infection. To reveal the potential interactions between ILCs and CA16 infection, the expression levels of genes related to ILC activation in CA16-infected human tracheal epithelial cells (16HBE) and mouse respiratory tract epithelial cells (CP-M175) stimulated by adjuvants formulated CA16-inactivated antigen were firstly determined. Then, a formulated experimental CA16-inactivated vaccine was used to immunize BALB/c mice through nasal route, and the relationship between ILCs and viral antigens in the respiratory mucosa was analyzed. Both CA16 live virus and inactivated virus particles could induce upregulation of various molecules required for the activation of ILCs and stimulate transcription and expression of cytokines, which were secreted by activated ILCs, no matter in vitro and in vivo. Moreover, immunofluorescence and confocal microscopic results showed that the viral antigen was co-localized with ILC1/ILC3. Finally, the anti-CA16 neutralizing antibodies and specific cellular immune response in mice of four different immunization pathways/immunization procedures were tested. The results suggested that the mice immunized with the formulated CA16-inactivated vaccine could induce an effective antiviral immune response in vivo. In conclusion, CA16 antigen can induce an effective immune response by activating ILCs.
王永蓉1，廉亚茹1,2，蒋国润1，范胜涛1，冯敏1，杨二霞2，姜莉2，董承红2，赵志梅1，王丽春1，廖芸1，张莹1，李琦涵1. 柯萨奇病毒 A16型抗原与呼吸道黏膜上皮组织内先天淋巴细胞的相互关系及其疫苗应用价值[J]. 微生物与感染, 2018, 13(6): 350-361.
WANG Yongrong1, LIAN Yaru1,2, JIANG Guorun1, FAN Shengtao1, FENG Min1, YANG Erxia2, JIANG Li2, DONG Chenghong2, ZHAO Zhimei1, WANG Lichun1, LIAO Yun1, ZHANG Ying1, LI Qihan1. Relationship between coxackievirus A16 antigen and innate lymphoid cells in respiratory tract epithelia and immunological analysis of its vaccine development. JOURNAL OF MICROBES AND INFECTIONS, 2018, 13(6): 350-361.
