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Sequencing analysis of the antigens included in the four-component  vaccine against serogroup B meningococcus in Czech isolates of Neisseria meningitidis from 2007–2013


Authors: P. Křížová;  M. Musílek;  Z. Vacková;  Z. Bečvářová;  J. Kozáková
Authors‘ workplace: Národní referenční laboratoř pro meningokokové nákazy, Centrum epidemiologie a mikrobiologie, Státní zdravotní ústav, Praha
Published in: Epidemiol. Mikrobiol. Imunol. 63, 2014, č. 1, s. 61-68
Category: Review articles, original papers, case report

Overview

Objective:
Study of the antigens included in the newly registered four-component vaccine against meningococcus B (MenB vaccine) produced by the reverse vaccinology method and assessment of the potential of the vaccine for use in the Czech Republic.

Material and Methods:
Czech isolates of Neisseria meningitidis were screened for four antigens: fHbp (factor H binding protein), NHBA (Neisseria heparin binding antigen), NadA (neisserial adhesin A), and PorA P1.4 outer membrane protein. A total of 304 N. meningitidis isolates from 2007-2013 were included in the study: 262 isolates from invasive meningococcal disease (IMD) (203 serogroup B isolates and 59 non-B isolates) and 42 isolates from healthy carriers.

Results:
The gene encoding the fHbp peptide was detected in all study isolates from both IMD cases and healthy carriers. The two types of isolates differed in the distribution of fHbp variants. The fHbp1 variant prevailed in the IMD isolates (both B and non-B) while the fHbp2 variant was expressed more often in the carrier isolates. The presence of the nhba gene encoding the NHBA peptide was revealed in all study isolates from both IMD cases and healthy carriers. The serogroup B isolates from IMD cases differed from the non-B isolates from IMD cases and from the carrier isolates in the distribution of NHBA variants. The presence of the nadA gene encoding the NadA peptide was only found in 26.6% of serogroup B isolates from IMD cases in comparison to 40.7% of non-B isolates from IMD cases. As few as 4.8% of isolates from healthy carriers harboured the nadA gene. The PorA P1.4 protein included in the new MenB vaccine was only detected in two serogroup B isolates from IMD cases (of the total of 262 serogroup B and non-B isolates from IMD cases) and in none of the isolates from healthy carriers. Isolates from both B and non-B IMD cases were positive most often for the combination of the antigens NHBA + fHbp1, followed by the NHBA antigen alone and then by the combination NHBA + fHbp1 + NadA-1+2/3. Isolates from healthy carriers showed a different antigen distribution pattern: the NHBA antigen alone was the most widespread, followed by the combination NHBA + fHbp1.

Conclusions:
The antigens included in the four-component MenB vaccine were revealed by sequencing in a large proportion of the Czech isolates of N. menin­gitidis from both IMD cases and healthy carriers. This four-component vaccine registered in Europe since January 2013 has proven suitable for use in the Czech Republic.

Keywords:
MenB vaccine – GNA (genome-derived neisserial antigens) – fHbp (factor H binding protein) – NHBA (Neisseria heparin binding antigen) – NadA (neisserial adhesin A) – PorA P1.4 outer membrane protein


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Hygiene and epidemiology Medical virology Clinical microbiology

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Epidemiology, Microbiology, Immunology

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