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Published on: November 5, 2019
Human antibody responses to the meningococcal factor H binding protein (LP2086) during invasive disease, colonization
Dlawer A A Ala'aldeen1, Mike Flint, Neil J Oldfield
1Molecular Bacteriology and Immunology Group, Institute of Infection, Immunity & Inflammation, Centre for Biomolecular Sciences, University of Nottingham, Nottingham NG7 2RD, United Kingdom. daa@nottingham.ac.uk
Abstract:
Recombinant forms of Neisseria meningitidis factor H binding protein (fHBP) are undergoing clinical trials in candidate vaccines against serogroup B meningococcal disease. Little is known, however, about the host response to fHBP during natural carriage and disease. Here we report a longitudinal study of the antibody response to fHBP in healthy meningococcal carriers and non-carriers, and in patients with invasive meningococcal disease. Using a highly sensitive quantitative immunoassay, anti-fHBP antibodies were detected in sera from all healthy carriers and non-carriers. Carriers had significantly higher anti-fHBP antibody concentrations than non-carriers. Antibody responses similar to those seen in non-carrier subjects were detected in the sera of patients with invasive disease upon their admission to the hospital. The serum anti-fHBP antibody concentrations in these patients generally rose to reach levels similar to those seen in carriers. No correlation between levels of surface fHBP expressed in vitro by the infecting N. meningitidis strain and the magnitude of antibody responses was observed. These data suggest that fHBP is expressed in vivo during both carriage and invasive disease at levels high enough to elicit a robust antibody response.
Insights
Antibody levels against Neisseria meningitidis factor H binding protein (fHBP) were measured in carriers, non-carriers, and patients with invasive disease. Carriers showed higher anti-fHBP antibodies, suggesting in vivo expression during carriage and disease.
Area of Science:
- Immunology
- Microbiology
- Vaccinology
Background:
- Neisseria meningitidis serogroup B causes significant disease.
- Factor H binding protein (fHBP) is a key target in developing vaccines against serogroup B.
- Limited understanding exists regarding host antibody responses to fHBP during natural meningococcal carriage and invasive disease.
Purpose of the Study:
- To investigate the longitudinal antibody response to fHBP in individuals with and without Neisseria meningitidis carriage, and in patients experiencing invasive meningococcal disease.
- To determine if fHBP elicits a detectable antibody response in vivo during natural infection or carriage.
Main Methods:
- A longitudinal study design was employed.
- Quantitative immunoassay was used to measure anti-fHBP antibody concentrations in serum samples.
- Sera were collected from healthy meningococcal carriers, healthy non-carriers, and patients with invasive meningococcal disease.
Main Results:
- Anti-fHBP antibodies were detected in all study participants (carriers, non-carriers, and patients).
- Healthy carriers exhibited significantly higher anti-fHBP antibody concentrations compared to non-carriers.
- Patients with invasive meningococcal disease showed antibody responses upon hospital admission that rose to levels comparable to carriers.
- No correlation was found between in vitro expressed surface fHBP levels and antibody response magnitude.
Conclusions:
- Factor H binding protein (fHBP) elicits a robust antibody response during natural Neisseria meningitidis carriage and invasive disease.
- fHBP is likely expressed in vivo at sufficient levels during both carriage and disease to stimulate antibody production.
- Understanding these natural antibody responses provides crucial insights for the development and efficacy of fHBP-based vaccines.
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