Inactivated influenza vaccine formulated with single-stranded RNA-based adjuvant confers mucosal immunity and cross-protection against influenza virus infection |
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| Affiliation: | 1. Department of Biotechnology, The Catholic University of Korea, Bucheon 14662, Republic of Korea;2. Department of R&D, SK bioscience, Pangyoro 332, Bundang-gu, Republic of Korea;3. Scripps Korea Antibody Institute, Chuncheon, Kangwon-Do 24341, Republic of Korea;4. SML Genetree Research Department of Research and Development, SML Genetree, Seoul, Baumero 225, Seocho-gu 06740, Republic of Korea;1. Department of Medical Microbiology, University of Groningen and University Medical Center Groningen, Antonius Deusinglaan 1, 9713 AV Groningen, The Netherlands;2. Department of Pharmaceutical Technology and Biopharmacy, University of Groningen, Antonius Deusinglaan 1, 9713 AV Groningen, The Netherlands;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. Trudeau Institute, Inc., Saranac Lake, NY, USA;2. Infectious Disease Research Institute, Seattle, WA, USA;3. University of Connecticut School of Medicine, Department of Immunology and Center on Aging, Farmington, CT, USA;1. Department of Pharmaceutical Technology and Biopharmacy, University of Groningen, Antonius Deusinglaan 1, 9713 AV Groningen, The Netherlands;2. Vaxine Pty Ltd., Flinders Medical Centre, Bedford Park, Adelaide 5042, Australia;3. Department of Diabetes and Endocrinology, Flinders Medical Centre/Flinders University, Adelaide 5042, Australia;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. Food Animal Health Research Program, Ohio Agricultural Research and Development Center, The Ohio State University, Wooster, OH, USA;2. Poultry Diseases Department, Faculty of Veterinary Medicine, Cairo University, Cairo, Egypt;3. Division of Infectious Diseases, Cincinnati Children''s Hospital Medical Center, Cincinnati, OH, USA;4. Department of Veterinary Preventive Medicine, College of Veterinary Medicine, The Ohio State University, Columbus, OH, USA |
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| Abstract: | Influenza vaccination is considered the most valuable means to prevent and control seasonal influenza infections, which causes various clinical symptoms, ranging from mild cough and fever to even death. Among various influenza vaccine types, the inactivated subunit type is known to provide improved safety with reduced reactogenicity. However, there are some drawbacks associated with inactivated subunit type vaccines, with the main ones being its low immunogenicity and the induction of Th2-biased immune responses. In this study, we investigated the role of a single-stranded RNA (ssRNA) derived from the intergenic region in the internal ribosome entry site of the Cricket paralysis virus as an adjuvant rather than the universal vaccine for a seasonal inactivated subunit influenza vaccine. The ssRNA adjuvant stimulated not only well-balanced cellular (indicated by IgG2a, IFN-γ, IL-2, and TNF-α) and humoral (indicated by IgG1 and IL-4) immune responses but also a mucosal immune response (indicated by IgA), a key protector against respiratory virus infections. It also increases the HI titer, the surrogate marker of influenza vaccine efficacy. Furthermore, ssRNA adjuvant confers cross-protective immune responses against heterologous influenza virus infection while promoting enhanced viral clearance. Moreover, ssRNA adjuvant increases the number of memory CD4+ and CD8+ T cells, which can be expected to induce long-term immune responses. Therefore, this ssRNA-adjuvanted seasonal inactivated subunit influenza vaccine might be the best influenza vaccine generating robust humoral and cellular immune responses and conferring cross-protective and long-term immunity. |
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