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FbaA- and M protein-based multi-epitope vaccine elicits strong protective immune responses against group A streptococcus in mouse model
Institution:1. Department of Immunology, Basic Medical College, Hebei Medical University, Shijiazhuang 050017, China;2. Key Laboratory of Medical Molecular Virology of Ministries of Education and Health, Shanghai Medical College and Institute of Medical Microbiology, Fudan University, Shanghai 200032, China;3. Third Hospital of Hebei Medical University, Shijiazhuang 050000, China;1. Guangzhou University of Chinese Medicine, Guangzhou 510006, China;2. Institute of Tropical Medicine, Guangzhou University of Chinese Medicine, Guangzhou 510405, China;3. Dongguan Mathematical Engineering Academy of Chinese Medicine, Guangzhou University of Traditional Chinese Medicine, Dongguan 523808, China;1. State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, China;2. The Cooperative Innovation Center for Sustainable Pig Production, Huazhong Agricultural University, Wuhan 430070, China;3. Key Laboratory of Development of Veterinary Diagnostic Products, Ministry of Agriculture, Huazhong Agricultural University, Wuhan 430070, China;2. Department of Pathology, Yokohama City University School of Medicine, Yokohama, Japan;4. Emory University School of Medicine and Children''s Healthcare of Atlanta, Atlanta, GA;11. Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN;1. State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, Hubei, 430070, China;2. Hubei Key Laboratory of Animal Embryo and Molecular Breeding, Institute of Animal Husbandry and Veterinary Sciences, Hubei Academy of Agricultural Sciences, Wuhan 430070, China;3. The Cooperative Innovation Center for Sustainable Pig Production, Huazhong Agricultural University, Wuhan 430070, China;1. Unité de Génétique Moléculaire des Bunyavirus, Institut Pasteur, 25 rue du Dr Roux, Paris, France;2. Unité Interactions Moléculaires Flavivirus-Hôtes, Institut Pasteur, 25 rue du Dr Roux, Paris, France
Abstract:We report the construction of a recombinant multivalent vaccine against group A streptococcus (GAS), designated F7M5. It contains seven predominant epitopes of FbaA identified by phage display technology, five non-tissue cross-reactive M protein fragments expressed on four selected serotypes prevalent in China, a Trojan antigen (TA) and a poly-alanine DR epitope (PADRE). BALB/c mice were immunized subcutaneously with F7M5 formulated with Freund's adjuvant, using recombinant FbaA and M protein in parallel as control. Using enzyme-linked immunosorbent assay (ELISA), mouse immune sera were assayed for IgG titers, IgG subclasses, and binding of F7M5 with M1GAS. Results indicated that the multivalent vaccine was highly immunogenic and elicited a balanced IgG1/IgG2a response. We also tested the reactivity of F7M5 to antistreptolysin O (ASO) antibodies in sera of GAS-infected patients and found a 95.8% positive rate, indicating that the epitopes of the vaccine were widely expressed in the prevalent serotypes of GAS. More importantly, the F7M5 vaccine elicited strong protective immune responses against lethal-dose challenge with a survival rate of 90%, but induced no cross-reactions or pathological lesions in mouse model, suggesting that F7M5 can be further developed as an effective and safe anti-GAS vaccine.
Keywords:Group A streptococcus (GAS)  Epitope  Vaccine  FbaA  M protein
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