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Understanding immunogenicity assessments for meningococcal serogroup B vaccines
Paul Balmer1, Johannes Beeslaar2, Jamie Findlow3
1Vaccine Medical Development, Scientific & Clinical Affairs, Pfizer Inc, Collegeville, PA, USA.
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.
Insights
Serum bactericidal antibody (SBA) assays, including rabbit (rSBA) and human (hSBA) complement methods, are crucial for evaluating meningococcal vaccine efficacy. This study clarifies the use of hSBA assays for serogroup B (MenB) vaccines, highlighting differences in their application for licensure.
Area of Science:
- Immunology
- Vaccinology
- Microbiology
Background:
- Invasive meningococcal disease (IMD) poses significant health risks, necessitating effective vaccines against common serogroups (A, B, C, W, Y).
- Traditional field efficacy trials for IMD vaccines are challenging due to low disease incidence.
- Serum bactericidal antibody (SBA) assays, using rabbit (rSBA) or human (hSBA) complement, serve as in vitro surrogates for vaccine efficacy and licensure.
Purpose of the Study:
- To describe the application of human serum bactericidal antibody (hSBA) assays for evaluating meningococcal serogroup B (MenB) vaccine efficacy.
- To clarify the complexities and differences in hSBA assay utilization for MenB vaccine licensure compared to other serogroups.
- To highlight how recently approved MenB vaccines employ hSBA assays to demonstrate broad protection.
Main Methods:
- Utilized rabbit serum bactericidal antibody (rSBA) assays for serogroups A, C, W, and Y, with a correlate of protection titer ≥1:8.
- Employed human serum bactericidal antibody (hSBA) assays for serogroup B (MenB) vaccines, with a correlate of protection titer ≥1:4.
- Applied multiple test strains in hSBA assays for MenB vaccines to account for antigenic variability of surface proteins.
Main Results:
- Established rSBA assays as standard for evaluating MenACWY vaccines, requiring a single conserved polysaccharide capsule strain per serogroup.
- Demonstrated the necessity of hSBA assays for MenB vaccines due to the antigenic diversity of surface proteins, requiring multiple test strains.
- Highlighted distinct approaches in clinical studies using hSBA assays for two recently approved MenB vaccines.
Conclusions:
- Serum bactericidal antibody (SBA) assays are indispensable tools for meningococcal vaccine licensure, with distinct methodologies for polysaccharide conjugate (MenACWY) and protein-based (MenB) vaccines.
- Human serum bactericidal antibody (hSBA) assays are critical for assessing MenB vaccine efficacy, requiring careful consideration of antigenic diversity.
- Understanding the nuances of hSBA assay application is essential for interpreting MenB vaccine data and ensuring broad protection against invasive meningococcal disease.
