Development of an FHbp-CTB holotoxin-like chimera and the elicitation of bactericidal antibodies against serogroup B Neisseria meningitidis |
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| Affiliation: | 1. Institute of Preventive Veterinary Medicine & Zhejiang Provincial Key Laboratory of Preventive Veterinary Medicine, Zhejiang University, Hangzhou 310058, China;2. School of Marine Science, Ningbo University, Ningbo 315211, China;3. Laboratory for Evolution & Development, Institute of Evolution & Marine Biodiversity and Department of Marine Biology, Ocean University of China, Qingdao 266003, China;1. Department of Chemistry and Biochemistry, Seton Hall University, 400 South Orange Avenue, South Orange, NJ 07079, United States;2. Department of Chemistry and Biochemistry, Queens College, City University of New York, 65-30 Kissena Blvd., Flushing, NY 11367, United States;1. Department of Aerospace Engineering, Sharif University of Technology, Tehran 11115-8639, Iran;2. Department of Mechanical Engineering, Sharif University of Technology, Tehran 11115-9567, Iran;1. Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Italy;2. Karolinska Institut, Stockholm, Sweden;3. Office of Birth and Childhood, Brussels, Belgium;1. Division of Infectious Disease, Wadsworth Center, New York State Department of Health, Albany, NY 12208, United States;2. Department of Biomedical Sciences, University at Albany School of Public Health, Albany, NY 12201, United States |
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| Abstract: | The Neisseria meningitidis factor H binding protein (FHbp) is an important virulence factor and vaccine antigen contained in both USA licensed serogroup B meningococcal vaccines. Recent studies in human factor H (hFH) transgenic mice suggest that hFH-FHbp interactions lower FHbp-elicited immunogenicity. To provide tools with which to characterize and potentially improve FHbp immunogenicity, we developed an FHbp-cholera holotoxin-like chimera vaccine expression system in Escherichia coli that utilizes cholera toxin B (CTB) as both a scaffold and adjuvant for FHbp. We developed FHbp–CTB chimeras using a wild-type (WT) FHbp and a low hFH-binding FHbp mutant R41S. Both chimeras bound to GM1 ganglioside and were recognized by the FHbp-specific monoclonal antibody JAR4. The R41S mutant had greatly reduced hFH binding compared to the WT FHbp-CTB chimera. WT and R41S FHbp-CTB chimeric antigens were compared to equimolar amounts of FHbp admixed with CTB or FHbp alone in mouse immunogenicity studies. The chimeras were significantly more immunogenic than FHbp alone or mixed with CTB, and elicited bactericidal antibodies against a panel of MenB isolates. This study demonstrates a unique and simple method for studying FHbp immunogenicity. The chimeric approach may facilitate studies of other protein-based antigens targeting pathogenic Neisseria and lay groundwork for the development of new protein based vaccines against meningococcal and gonococcal disease. |
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| Keywords: | Factor H binding protein Cholera toxin B subunit Vaccine Bactericidal antibody |
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