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Use of recombinant flagellin in oil-in-water emulsions enhances hemagglutinin-specific mucosal IgA production and IL-17 secreting T cells against H5N1 avian influenza virus infection
Institution:1. Institute of Biotechnology, Department of Life Science, National Tsing Hua University, Hsinchu, Taiwan;2. Genomics Research Center, Academia Sinica, Taipei, Taiwan;3. National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Zhunan, Taiwan;4. Department of Pediatrics, National Taiwan University Hospital, Taipei, Taiwan;5. Department of Medical Science, National Tsing Hua University, Hsinchu, Taiwan;1. Laboratório de Macromoléculas, Bio-Manguinhos, Fundação Oswaldo Cruz, Rio de Janeiro, Brazil;2. Laboratório de Tecnologia Bacteriana, Bio-Manguinhos, Fundação Oswaldo Cruz, Rio de Janeiro, Brazil;3. Departamento de Vacinas Bacterianas, Bio-Manguinhos, Fundação Oswaldo Cruz, Rio de Janeiro, Brazil;4. Programa de Vacinas Bacterianas, Bio-Manguinhos, Fundação Oswaldo Cruz, Rio de Janeiro, Brazil;5. Escola de Química, Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro, Brazil;1. College of Veterinary Medicine (BK21 Plus Program), Chungnam National University, Daejeon, Republic of Korea;2. BioLeaders Corporation, Daejeon, Republic of Korea;3. Faculty of Veterinary Medicine, Chittagong Veterinary and Animal Sciences University, Chittagong 4202, Bangladesh;4. Foot and Mouth Disease Division, Animal Quarantine and Inspection Agency, Anyang, Republic of Korea;1. Institute of Veterinary Immunology & Engineering, Jiangsu Academy of Agricultural Sciences, Nanjing 210014, China;2. National Research Center of Engineering and Technology for Veterinary Biologicals, Jiangsu Academy of Agricultural Sciences, Nanjing 210014, China;3. Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou 225009, China;1. Department of Microbiology and Immunology, Wake Forest School of Medicine, Winston-Salem, NC, United States;2. Department of Biostatistical Sciences, Wake Forest School of Medicine, Winston-Salem, NC, United States;3. Animal Resources Program, Wake Forest School of Medicine, Winston-Salem, NC, United States;4. Department of Pathology, Section of Comparative Medicine, Wake Forest School of Medicine, Winston-Salem, NC, United States;5. Department of Chemistry, Wake Forest University, United States;1. College of Animal Science and Technology, Jilin Provincial Engineering Research Center of Animal Probiotics, Key Laboratory of Animal Production and Product Quality Safety of Ministry of Education, Jilin Agricultural University, Changchun, 130118, China;2. Shandong Baolai-Leelai Bio-Tech Co., LTD, Taian, Shandong Province, 171000, China;1. College of Veterinary Medicine, Chungnam National University, Daejeon, Republic of Korea;2. Faculty of Veterinary Medicine, Chittagong Veterinary and Animal Sciences University, Chittagong, Bangladesh;3. Faculty of Veterinary & Animal Science, Sylhet Agricultural University, Sylhet -3100, Bangladesh;4. BioLeaders Corporation, Daejeon, Republic of Korea;5. Department of Biochemistry and Biotechnology, University of Science and Technology Chittagong, Bangladesh
Abstract:Researchers are currently involved in a strong effort to find a safe and effective vaccine against highly pathogenic avian influenza H5N1 viruses. Toward that goal, we obtained soluble recombinant flagellin (FliC) of Salmonella typhimurium to be used as a mucosal adjuvant for H5HA subunit vaccine development. Intranasal immunization of H5HA antigen with recombinant FliC protein in an oil-in-water emulsion increased H5HA-specific IgG and IgA titers in sera, bronchoalveolar lavage fluids (BALFs), and nasal washes. Use of FliC adjuvant for intranasal immunization further augmented B-cell responses in mucosal environments via increased IgA titers in BALFs and nasal washes. Increases in IgA and IgG titers through the use of FliC adjuvant in intranasal immunization correlated with higher neutralizing antibody titers in sera and BALFs and higher numbers of IgG- and IgA-secreting B cells in spleen and cervical lymph nodes. High levels of IL-17A cytokine production were also found in stimulated T cells of spleen and cervical lymph node cells, only by intranasal immunization particularly with the use of FliC adjuvant in oil-in-water emulsions. These findings may provide useful information toward the development of H5HA mucosal influenza vaccines.
Keywords:Flagellin  Mucosal adjuvant  IgA  IL-17  H5N1 vaccine
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