Intranasal inoculate of influenza virus vaccine against lethal virus challenge |
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| Affiliation: | 1. National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China;2. Sinovac Biotech Co., Ltd., Beijing, China;1. Medigen, Inc., 8420 Gas House Pike, Suite S, Frederick, MD 21701, USA;2. Influenza Division, Centers for Disease Control and Prevention, 1600 Clifton Road N.E, Atlanta, GA, USA;1. National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Zhunan, 35053 Miaoli, Taiwan;2. Graduate Institute of Immunology, China Medical University, 40402 Taichung, Taiwan;1. Joint National Laboratory for Antibody Drug Engineering, Henan University, School of Basic Medical Sciences, Kaifeng, Henan Province, China;2. Institute of Military Veterinary, Academy of Military Medical Sciences, Changchun, Jilin Province, China;3. Key Lab of Cellular and Molecular Immunology, Henan University, School of Basic Medical Sciences, Kaifeng, Henan Province, China;4. Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou, Jiangsu Province, China;5. Changchun Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Changchun, Jilin Province, China;6. Institute of Laboratory Animal Sciences, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China;1. Vaccines Research, Novartis Vaccines, Siena, Italy;2. Vaccines Research, Novartis Vaccines, Cambridge, Massachusetts, United States;1. Department of Molecular and Medical Virology, Ruhr-University Bochum, Universitätsstraße 150, 44790 Bochum, Germany;2. Institute of Clinical and Molecular Virology, University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nürnberg, Schloßgarten 4, 91054 Erlangen, Germany;3. Institute for Virology, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany;4. Sirion Biotech, Am Klopferspitz 19, 82152 Martinsried, Germany |
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| Abstract: | ![]()
Vaccine adjuvants are essential for enhancing immune responses during vaccination. However, only a limited number of safe and effective adjuvants, especially mucosal adjuvants, are available for use in vaccines. The development of a practically applicable mucosal adjuvant is therefore urgently needed. Here, we showed that the non-toxic CTA1-DD adjuvant, which combined the full enzymatic activity of the A1 subunit of cholera toxin (CT) with two immunoglobulin-binding domains of Staphylococcus aureus protein A (SpA), promoted mucosal and systemic humoral and cell-mediated immune responses following intranasal administration with H1N1 split vaccine in mice. We demonstrated that CTA1-DD-adjuvant vaccine provided 100% protection against mortality and greatly reduced morbidity in a mouse model. We also showed that addition of CTA1-DD to the vaccine elicited significantly higher hemagglutination inhibition titers and IgG antibodies in sera than alum adjuvant. Furthermore, CTA1-DD significantly promoted the production of mucosal secretory IgA in lung lavages and vaginal lavages. We also showed that CTA1-DD could be used as a mucosal adjuvant to enhance T cell responses. Our results clearly indicated that CTA1-DD contributed to the elicitation of a protective cell-mediated immune response required for efficacious vaccination against influenza virus, which suggested that this adjuvant could be explored further as a clinically safe mucosal vaccine adjuvant for respiratory diseases and other mucosal diseases. |
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| Keywords: | Mucosal adjuvant CTA1-DD Influenza vaccine H1N1 |
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