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Review

Multivalent meningococcal serogroup B vaccines: challenges in predicting protection and measuring effectiveness

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Pages 1277-1287 | Published online: 23 Jul 2015
 

Abstract

Vaccines targeting Neisseria meningitidis serogroup B (MenB) have been attempted for 40 years. Monovalent outer membrane vesicle vaccines targeted at epidemic outbreaks have been successfully developed. Newer vaccines aim to induce antibodies to cross-reactive antigens, such as factor H binding protein (rLP2086) or a mix of outer membrane vesicle, factor H binding protein and other minor antigens (4CMenB). The true protective coverage among circulating MenB isolates afforded by these vaccines is unknown. Carefully conducted Phase IV post-implementation evaluations designed to measure specific effectiveness against major circulating MenB clonal lineages are needed to address the critical question of which antigens are linked to protection. Progress with whole-genome sequencing and bio-informatics may allow the composition of antigen mozaics based on two major outer membrane proteins: PorA and FetA.

Acknowledgements

The authors thank J Wolter (independent writer on behalf of Janssen) for writing assistance. All costs associated with development of this manuscript were funded by Janssen. The corresponding author had final responsibility for the decision to submit for publication.

Financial & competing interests disclosure

All costs associated with development of this manuscript were funded by Janssen; this included funding for the use of independent medical writing assistance. JT Poolman is an employee of Crucell Holland BV. P Richmond has undertaken sponsored clinical trials of meningococcal B vaccines for both Novartis and Pfizer and received travel support from Sanofi, Baxter and Pfizer to present clinical trial data at scientific meetings. P Richmond has received institutional funding for investigator initiated epidemiological studies from Novartis and GSK. He has been a member of scientific advisory boards for Pfizer and Janssen, but not received honoraria. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Key issues
  • Monovalent outer membrane vesicle (OMV) vaccines targeted at epidemic outbreaks induce a protective bactericidal antibody response likely directed against the variable major outer membrane protein PorA.

  • An alternative approach employed by new vaccines aims to induce antibodies to cross-reactive antigens, such as factor H binding protein (fHbp, rLP2086), or a mix of OMV, fHbp and other minor antigens (4CMenB). These vaccines rely on multiple minor proteins for adequate immunogenicity.

  • A single OMV was added to the initial 4CMenB formulations to improve immunogenicity and coverage.

  • Measurement of serum bactericidal activity (SBA) is the gold standard for demonstrating immunogenicity of meningococcal vaccines. Because of difficulties of using SBA on the scale needed to measure immunogenicity against a wide panel of meningococcal strains, alternative measures of immunogenicity have been developed: MATS and MEASURE.

  • The true protective strain coverage amongst circulating MenB isolates afforded by rLP2086 and 4CMenB is unknown. Correlations between MATS readouts with SBA suggest it may be a conservative measure of coverage. However, estimates using serum from infants <1 year of age are lacking to date.

  • Carefully conducted Phase IV post-implementation effectiveness evaluations are needed; set up in such a way as to measure specific effectiveness against major circulating MenB clonal lineages. Such studies are needed to address the critical question of which antigens are linked to protection in order to guide further optimization of MenB vaccine composition.

  • Bioinformatics could allow improved OMV vaccines using several major proteins, such as PorA, already demonstrated to be effective in monovalent OMV vaccines, and FetA.

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