Prevalence and genetic characteristics of 4CMenB and rLP2086 vaccine candidates among Neisseria meningitidis serogroup B strains, China

Abstract

Objective: To systematically investigate the prevalence and genetic characteristics of 4CMenB and rLP2086 vaccine candidates among Neisseria meningitidis serogroup B (NmB) in China.

Methods: A total of 485 NmB strains isolated in 29 provinces of China between 1968 and 2016 were selected from the culture collection of the national reference laboratory according to the isolation year, location, and source. Multi-locus sequence typing (MLST) and porA gene sequencing were performed on all 485 study strains; PCR was used to detect the fHbp, nadA, and nhba gene of 432 strains; positive amplification products from the fHbp and nadA genes from all strains, as well as those of the nhba gene from 172 representative strains, were sequenced.

Results: MLST results showed that the predominant (putative) clonal complexes (CCs) of NmB isolates have changed over time in China. While strains that could not be assigned to existing (p)CCs were the biggest proportion, CC4821 was the most prevalent lineage (36.0%) since 2005. PCR and sequence analysis revealed that the 4CMenB and rLP2086 vaccine candidates were highly diverse. Respectively, 152 PorA genotypes and 83 VR2 sequences were identified with significant diversity within a single CC; the complete nadA gene was found in ten of 432 study strains; fHbp was present in most strains (422/432) with variant 2 predominating (82.9%) in both patient- and carrier- derived isolates; almost all strains harbored the nhba gene while sequences were diverse.

Conclusions: With regards to clonal lineages and vaccine candidate proteins, NmB isolates from China were generally diverse. Further studies should be performed to evaluate the cross-protection of present vaccines against Chinese NmB strains.

Keywords: China; Clonal complex; Neisseria meningitidis serogroup B; Vaccine candidate.