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Published on: November 5, 2019
Characterization of Neisseria meningitidis isolates that do not express the virulence factor and vaccine antigen
Jay Lucidarme1, Lionel Tan, Rachel M Exley
1Vaccine Evaluation Unit, Health Protection Agency, North West Regional Laboratory, P.O. Box 209, Clinical Sciences Building II, Manchester Royal Infirmary, Manchester M13 9WZ, United Kingdom.
Abstract:
Neisseria meningitidis remains a leading cause of bacterial sepsis and meningitis. Complement is a key component of natural immunity against this important human pathogen, which has evolved multiple mechanisms to evade complement-mediated lysis. One approach adopted by the meningococcus is to recruit a human negative regulator of the complement system, factor H (fH), to its surface via a lipoprotein, factor H binding protein (fHbp). Additionally, fHbp is a key antigen in vaccines currently being evaluated in clinical trials. Here we characterize strains of N. meningitidis from several distinct clonal complexes which do not express fHbp; all strains were recovered from patients with disseminated meningococcal disease. We demonstrate that these strains have either a frameshift mutation in the fHbp open reading frame or have entirely lost fHbp and some flanking sequences. No fH binding was detected to other ligands among the fHbp-negative strains. The implications of these findings for meningococcal pathogenesis and prevention are discussed.
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