Intranasal immunization with recombinant Vaccinia virus Tiantan harboring Zaire Ebola virus gp elicited systemic and mucosal neutralizing antibody in mice |
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| Affiliation: | 1. Department of Health Services Management, School of Health Services Management, Anhui Medical University, Hefei, Anhui, China;2. School of Social Development and Public Policy, Beijing Normal University, Beijing, China;3. Chinese Center for Disease Control and Prevention, Beijing, China;4. School of Medicine and Health Management, Tongji Medical College of Huazhong University of Science & Technology, Wuhan, China;5. The First Clinical Medical School, Anhui Medical University, Hefei, Anhui, China;1. The Jenner Institute, University of Oxford, Oxford, UK;2. Respiratory Virus Unit, Public Health England, London, UK;1. Department of Immunology & Defense Mechanism, College of Biotechnology, Sardar Vallabhbhai Patel University of Agriculture and Technology, Meerut, 250110, India;2. CADRAD, Indian Veterinary Research Institute, Izatnagar, 243122, India;3. Department of Veterinary Pharmacology, College of Veterinary and Animal Sciences, Sardar Vallabhbhai Patel University of Agriculture & Technology, Meerut, 250110, India;4. Division of Goat Health, Central Institute for Research on Goats, Farha, Mathura, 281122, India;5. Department of Veterinary Medicine, College of Veterinary and Animal Sciences, Sardar Vallabhbhai Patel University of Agriculture & Technology, Meerut, 250110, India;6. Department of Veterinary Microbiology, College of Veterinary and Animal Sciences, DUVASU, Mathura, 281001, India;1. Kaiser Permanente Southern California, USA;2. Kaiser Permanente Northern California, USA;3. Immunization Safety Office, Centers for Disease Control and Prevention, USA;4. Kaiser Permanente Northwest, USA;5. Marshfield Clinic Research Institute, USA |
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| Abstract: | Accumulating literature revealed that human mucosa was likely one of the important routes for EBOV attachment and further infection. Therefore inducing effective mucosal immune responses play key role in preventing the virus infection. Vaccinia virus Tiantan strain (VV) was a remarkably attenuated poxvirus, which has been broadly exploited as a multifunctional vector during the development of genetically recombinant vaccine and cancer therapeutic agent. In this study, we generated a recombinant VV harboring EBOV gp (VV-Egp) that was used to immunize mice, followed by assessing immune responses, particularly the mucosal immune responses to EBOV GP. A stable and further attenuated VV-Egp, in which the VV ha gene was replaced with the EBOV gp, was generated. In BALB/c mouse model, intranasal immunization with VV-Egp elicited robust humoral and cellular immune responses, including high level of neutralizing serum IgG and IgA against EBOV, and a large amount of GP-specific IFN-γ secreting lymphocytes. More importantly, EBOV GP-specific neutralizing secreted IgA (sIgA) in nasal wash and both sIgA and IgG in vaginal wash were induced. In summary, immunization with a safe and stable recombinant VV carrying a single EBOV gp conferred robust systemic immune response and mucosal neutralizing antibodies, indicating that the recombinant virus could be utilized as a viral vector for plug-and-play universal platform in mucosal vaccine development. |
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| Keywords: | Vaccinia virus vector Ebola virus GP Mucosal sIgA Neutralization |
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