Understanding immunogenicity assessments for meningococcal serogroup B vaccines

ABSTRACT

Invasive meningococcal disease (IMD) is a potentially devastating infection associated with high mortality and long-term sequelae; however, vaccines are available to protect against the five common disease-causing serogroups (A, B, C, W, and Y). Because traditional field efficacy clinical trials were not feasible due to low IMD incidence that necessitates a very large number of participants, serum bactericidal antibody (SBA) assays using rabbit (rSBA) or human (hSBA) complement were established as in vitro surrogates of meningococcal vaccine efficacy and are now routinely used to support vaccine licensure. Specifically, rSBA assays have been used to evaluate responses to meningococcal capsular polysaccharide–protein conjugate vaccines against serogroups A, C, W, and Y; the accepted correlate of protection for rSBA assays is a titer ≥1:8. Importantly, because the bacterial capsular polysaccharide antigen is conserved across strains, only one test strain that expresses an invariant polysaccharide capsule for each serogroup is required to assess coverage. rSBA assays are unsuitable for subcapsular protein-based serogroup B (MenB) vaccines, and therefore, hSBA assays have been used for licensure; titers ≥1:4 are considered the correlate of protection against IMD for hSBA. In contrast to MenACWY vaccines, because bacterial surface proteins are antigenically variable, MenB vaccines must be tested with hSBA assays using multiple test strains that represent the antigenic diversity of disease-causing isolates. As this complexity regarding SBA assessment methods can make data interpretation difficult, herein we describe the use of hSBA assays to evaluate MenB vaccine efficacy and to support licensure. In addition, we highlight how the two recently approved MenB vaccines differ in their use of hSBA assays in clinical studies to demonstrate broad protection against MenB IMD.

KEYWORDS:

• hSBA
• meningitis
• meningococcal vaccines
• rSBA
• serum bactericidal antibody assay

Acknowledgments

Editorial support for the development of this manuscript was provided by Jill E. Kolesar, PhD, and Anna Stern, PhD, at Complete Healthcare Communications, LLC (North Wales, PA), a CHC Group company, and funded by Pfizer.

Declaration of interest

P Balmer, J Beeslaar, J Findlow, and A Srivastava are employees of Pfizer Inc and may hold stock or stock options.

Authors Contributions

All authors were involved in the study conception and design of this manuscript, the analysis and interpretation of data, and the drafting and revising of this manuscript.

Correction Statement

This article has been republished with minor changes. These changes do not impact the academic content of the article.

Additional information

Funding

This work was sponsored by Pfizer Inc.