Development of a high-growth enterovirus 71 vaccine candidate inducing cross-reactive neutralizing antibody responses |
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| Affiliation: | 1. National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Zhunan, Taiwan;2. Department of Veterinary Medicine, National Chung Hsing University, Taichung, Taiwan;3. Institute of Chemistry, Academia Sinica, Taipei, Taiwan;1. Odum School of Ecology, University of Georgia, Athens, GA, USA;2. Center for the Ecology of Infectious Diseases, University of Georgia, Athens, GA, USA;3. Center for the Study of Complex Systems, University of Michigan, Ann Arbor, MI, USA;4. Immunisation, Hepatitis and Blood Safety Department, National Infection Service, Public Health England, London, UK;5. Department of Ecology & Evolutionary Biology, University of Michigan, Ann Arbor, MI, USA;6. Department of Infectious Diseases, University of Georgia, Athens, GA, USA;1. Vaccine Research Center, Key Laboratory of Molecular Virology & Immunology, Institut Pasteur of Shanghai, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China;2. National Center for Protein Science – Shanghai, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 201210, China;5. Andhra Medical College and King George Hospital, Visakhapatnam, India;1. KEM Hospital Research Centre, Pune, India;6. Shri Shirdi Sai Baba Hospital, Vadu, India;2. Bharti Vidyapeeth Deemed University Medical College, Pune, India;3. Sri Ramachandra Medical Centre, Chennai, India;4. Krishna Institute of Medical Sciences, Karad, India;7. Serum Institute of India Pvt. Ltd., Pune, India;9. PATH, Seattle, USA;1. KEM Hospital Research Centre, Pune, India;2. Bharti Vidyapeeth Deemed University Medical College, Pune, India;3. Sri Ramachandra Medical Centre, Chennai, India;4. Krishna Institute of Medical Sciences, Karad, India;5. Andhra Medical College and King George Hospital, Visakhapatnam, India;7. Serum Institute of India Pvt. Ltd., Pune, India;8. PharmaJet, Golden, USA;9. PATH, Seattle, USA;1. College of Animal Science, Jilin University, Jilin 130062, China;2. State Key Laboratory of Pathogen & Biosecurity, Beijing Institute of Microbiology & Epidemiology, Beijing 100071, China;3. Liaocheng People’s Hospital, Shandong 252000, China;4. Tangshan Maternal and Child Health Care Hospital, Hebei 063000, China;5. Beijing Ditan Hospital, Capital Medical University, Beijing 100071, China;6. Changchun Hygeia Biotech Co, Ltd, Jilin 130000, China |
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| Abstract: | Although Enterovirus 71 (EV71) has only one serotype based on serum neutralization tests using hyperimmune animal antisera, three major genogroups (A, B and C) including eleven genotypes (A, B1-B2, and C1-C5) can be well classified based on phylogenetic analysis. Since 1997, large-scale EV71 epidemics occurred cyclically with different genotypes in the Asia-Pacific region. Therefore, development of EV71 vaccines is a national priority in several Asian countries. Currently, five vaccine candidates have been evaluated in clinical trials in China (three C4 candidates), Singapore (one B2 candidate), and Taiwan (one B4 candidate). Overall, the peak viral titers of these 5 vaccine candidates could only reach about 107 TCID50/mL. Moreover, genotypes of these 5 candidates are different from the current predominant genotype B5 in Taiwan and South-Eastern Asia. We adapted a high-growth EV71 genotype B5 (HG-B5) virus after multiple passages and plaque selections in Vero cells and the HG-B5 virus could reach high titers (>108 TCID50/mL) in a microcarrier-based cell culture system. The viral particles were further purified and formulated with alum adjuvant. After two doses of intramuscular immunization in rabbits, the HG-B5 vaccine candidate could induce cross-reactive neutralizing antibodies against the three major EV71 genogroups. In conclusion, a high-growth EV71 virus was successfully adapted in Vero cells and could induce broad spectrum neutralizing antibody titers against three (A, B5, and C4) genotypes in rabbits. |
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| Keywords: | Enterovirus 71 High-growth virus Vaccine development |
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