Correlates of protection for meningococcal surface protein vaccines: current approaches for the determination of breadth of coverage

ABSTRACT

Introduction

The two currently licensed surface protein non-capsular meningococcal serogroup B (MenB) vaccines both have the purpose of providing broad coverage against diverse MenB strains. However, the different antigen compositions and approaches used to assess breadth of coverage currently make direct comparisons complex.

Areas covered

In the second of two companion papers, we comprehensively review the serology and factors influencing breadth of coverage assessments for two currently licensed MenB vaccines.

Expert opinion

Surface protein MenB vaccines were developed using different approaches, resulting in unique formulations and thus their breadth of coverage. The surface proteins used as vaccine antigens can vary among meningococcal strains due to gene presence/absence, sequence diversity, and differences in protein expression. Assessment of the breadth of coverage provided by vaccines is influenced by the ability to induce cross-reactive functional immune responses to sequence diverse protein variants; the characteristics of the circulating invasive strains from specific geographic locations; methodological differences in the immunogenicity assays; differences in human immune responses between individuals; and the maintenance of protective antibody levels over time. Understanding the proportion of meningococcal strains, which are covered by the two licensed vaccines, is important in understanding protection from disease and public health use.

KEYWORDS:

• Correlates of protection
• invasive meningococcal disease
• Neisseria meningitidis
• vaccine
• vaccine effectiveness

Article highlights

• In the second of two companion papers, we compare how the two currently available meningococcal surface protein vaccines, 4CMenB and MenB-FHbp, have been assessed for breadth of coverage.

• The breadth of coverage afforded by meningococcal surface protein vaccines is driven by (1) the choice of protein antigens included in the vaccines and the ability to induce cross-reactive immune responses to diverse protein variants – this immune response can vary between individuals and be age-related; and (2) the susceptibility of circulating invasive MenB and other meningococcal strains from a geographic location – do these strains sufficiently express the protein(s) recognized by vaccine induced antibodies.

• Predicting the breadth of coverage is also influenced by the methodologic differences in the immune correlate of protection, which is the SBA assay using human complement (hSBA). Genotypic methods of predicting coverage are less reliable.

• Different approaches have been undertaken for the immunological assessment and prediction of breadth of coverage for 4CMenB and MenB-FHbp.

• 4CMenB assessment has primarily used four MenB indicator strains in the hSBA assay to independently measure responses against one of the four antigens. Responses against these ‘matched’ indicator strains do not provide information on cross-protection to diverse strains with different protein variants or lower expression levels. Coverage of 4CMenB against MenB isolates has therefore been predicted using the Meningococcal Antigen Typing System (MATS) which provides a binary ‘covered’ or ‘not covered’ outcome but which does not account for differences in responses between individuals or different age groups.

• Assessment of MenB-FHbp has primarily been undertaken in the hSBA assay using four primary and 10 additional MenB strains. All of these strains expressed a unique heterologous FHbp to those contained within the vaccine and all expressed the FHbp protein at low-medium levels. Responses against these 14 MenB strains was intended to provide breadth of coverage information as the FHbp variants and expression levels were representative of global diversity.

• Real-world effectiveness data are confirming that the meningococcal protein-based vaccines, licensed on the basis of hSBA, can prevent meningococcal disease caused by MenB and other serogroups; but have also demonstrated that meningococcal surface protein vaccines do not provide ubiquitous coverage. This evidence further emphasizes the importance of understanding factors influencing coverage and longitudinally assessing breadth of coverage.

List of abbreviations

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Acknowledgments

This publication made use of the PubMLST website available at https://pubmlst.org [42]. We would also like to thank the participants of study B1971048, the coordinating investigator Professor Lars Østergaard, and the research team.

Author contribution

All authors participated equally and substantially in manuscript development, including interpretation of literature, writing, revision, and intellectual contribution.

Declarations of Interest

J Findlow, P Liberator, AS Anderson, P Balmer and L Jodar are employees of Pfizer Inc and may hold stock or stock options. R Borrow performs contract research on behalf of Public Health England for GSK, Pfizer, and Sanofi Pasteur. DS Stephens performs research on N. meningitidis funded by the US National Institute of Allergy and Infectious Diseases of the National Institutes of Health. 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.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

All authors took part in manuscript development, and Pfizer was responsible for manuscript concept and funding of all publication costs.