#PAGE_PARAMS# #ADS_HEAD_SCRIPTS# #MICRODATA#

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


Sources

1. Tettelin H, Saunders NJ, Heidelberg J, et al. Complete geonome sequence of Neisseria meningitidis serogroup B strain MC58. Science 2000;287(5459):1767–1768.

2. Pizza M, Scarlato V, Masignani V, et al. Identification of vaccine candidates against serogroup B meningococcus by whole-genome sequencing. Science 2000;287(5459):1816–1820.

3. Rappuoli R. Reverse vaccinology, a genome-based approach to vaccine development. Vaccine 2001;19(17–19):2688–2691.

4. Capecchi B, Serruto D, Adu-Bobie J, et al. The geonome revolution in vaccine research. Curr Issues Mol Biol 2004;6(1):17–27.

5. Giuliani MM, Adu-Bobie J, Comanducci M, et al. A universal vaccine for serogroup B meningococcus. PNAS 2006;103(29):10834–10839.

6. Jacobsson S, Thulin S, Molling P, et al. Sequence constancies and variations in genes encoding three new meningococcal vaccine candidate antigens. Vaccine 2006;24:2161–2168.

7. Jacobsson S, Thulin Hedberg S, Molling P, et al. Prevalence and sequence variations of the genes encoding the five antigens included in the novel 5CVMB vaccine covering group B meningococcal disease. Vaccine 2009;27:1579–1584.

8. Beernink PT, Welsch JA, Harrison LH, et al. Prevalence of factor H-binding protein variants and NadA among meningococcal group B isolates from the United States: implications for the development of a multicomponent group B vaccine. J Infect Dis 2007;195(10):1472–1479.

9. Bambini S, Muzzi A, Olcen P, et al. Distribution and genetic variability of three vaccine components in a panel of strains representative of the diversity of serogroup B meningococcus. Vaccine 2009;27:2794–2803.

10. Beernink PT, Caugant DA, Welsch JA, et al. Meningococcal factor H-binding protein variants expressed by epidemic capsular group A, W-135, and X strains from Africa. JID 2009;199:1360–1368.

11. Comanducchi M, Bambini S, Caugant DA, et al. NadA diversity and carriage in Neisseria meningitidis. Infect Immun 2004;72(7):4217–4223.

12. Murphy E, Andrew L, Lee K-L, et al. Sequence diversity of the factor H binding protein vaccine candidate in epidemiologically relevant strains of serogroup B Neisseria meningitidis. JID 2009;200:379–389.

13. Lucidarme J, Comanducci M, Findlow J, et al. Characterization of fHbp, nhba (gna2132), nadA, porA, and sequence type in group B meningococcal case isolates collected in England and Wales during January 2008 and potential coverage of an investigational group B meningococcal vaccine. Clin Vaccine Immunol 2010;17(6):919–929.

14. Bettinger JA, Halperin SA, Scheifele DW, et al. Diversity of Canadian meningococcal serogroup B isolates and estimated coverage by an investigational meningococcal serogroup B vaccine (4CMenB). Vaccine 2014;/dx.doi.org/10.1016/j.vaccine.2013.03.063;32:124–130.

15. Cohn A, Comanducci M, Wang X et al. Prevalence and genetic diversity of candidate vaccine antigens among invasive Neisseria meningitidis isolates in the United States. Vaccine, 2011; doi:10.1016/j.vaccine.2011.04.092;29:4739–4744.

16. Donnelly J, Medini D, Boccadifuoco G, et al. Qualitative and quantitative assessment of meningococcal antigens to evaluace the potential strain coverage of protein-based vaccines. Proc Natl Acad Sci USA, 2010;107(45):19490–19495.

17. Vogel U, Taha MK, Vazquez JA, et al. Predicted strain coverage of a meningococcal multicomponent vaccine (4CMenB) in Europe: a qualitative and quantitative assessment. Lancet Infect Dis, 2013;13(5):416–425.

18. Frosi G, Biolchi A, Lo Sapio M et al. Bactericidal antipody ­against a representative epidemiological meningococcal serogroup B panel confirms that MATS underestimates 4CMenB vaccine strain coverage. Vaccine 2013;31(43):4968–4974.

19. Esposito S, Prymula R, Vesikari T et al. Immunogenicity and safety of an investigational multicomponent, recombinant, meningococcal serogroup B vaccine (4CMenB) administered concomitantly with routine infant and child vaccinations: results of two randomised trials. Lancet 2013;381:825–835.

20. Andrew L, Kwok-Leung L, Murphy E, et al. Sequence Diversity of the Factor H Binding Protein Vaccine Candidate in Epidemiologically Relevant Strains of Serogroup B Neisseria Meningitidis. The Journal of Infectious Diseases 2009; 200:379–389.

21. Harris SL, Murphy E, Zhu D, et al. Preclinical evidence for the potential of a bivalent fHBP vaccine to prevent Neisseria Meningitidis serogroup C disease. Human Vaccines 2011;7Suppl:68–74.

22. Hubert K, Devos N, Mordhorst I, et al. ZnuD a Potential Candidate for a Simple and Universal Neisseria meningitidis Vaccine. Infection and Immunity 2013;81(6):1915–1927.

23. Křížová P, Vacková Z, Musílek M, Kozáková J. Invazivní meningokokové onemocnění v České republice – analýza epidemiologické situace a doporučení k vakcinační strategii. Epidemiologie, Mikrobiologie, Imunologie 2013, 62(4), 138–147.

24. Křížová P. Invazivní meningokokové onemocnění – aktuální epidemiologická situace a možnosti očkování proti meningokokům. Vakcinologie, 2014, 8(1), 6–10.

Labels
Hygiene and epidemiology Medical virology Clinical microbiology

Article was published in

Epidemiology, Microbiology, Immunology

Issue 1

2014 Issue 1

Most read in this issue
Login
Forgotten password

Enter the email address that you registered with. We will send you instructions on how to set a new password.

Login

Don‘t have an account?  Create new account

#ADS_BOTTOM_SCRIPTS#