A Newly-Identified Polymorphism in Rhesus Macaque Complement Factor H Modulates Binding Affinity for Meningococcal...

Area of Science:

• Immunology
• Vaccinology
• Protein Biochemistry

Background:

• Meningococcal serogroup B vaccines utilize Factor H binding protein (FHbp) to elicit immune responses.
• Factor H (FH) binding to FHbp was previously believed to be specific to human and chimpanzee FH.
• Polymorphisms in rhesus macaque FH, specifically at position 352, influence FHbp binding affinity.

Purpose of the Study:

• To investigate the impact of additional polymorphisms in rhesus macaque FH on FHbp binding.
• To characterize the binding affinities of different FH allelic variants to FHbp.
• To identify macaque FH genotypes with binding characteristics similar to humans for vaccine immunogenicity studies.

Main Methods:

• Analysis of FH polymorphisms at positions 352 and 360 in 43 rhesus macaques.
• Measurement of FH binding affinity to FHbp using surface plasmon resonance.
• Genotyping of macaque FH allelic variants and their combinations.

Main Results:

• A second FH polymorphism at position 360, alongside position 352, affects FHbp binding in macaques.
• Three allelic variants (HP, YS, YP) at positions 352 and 360 determine FH binding affinity to FHbp.
• Macaque FH variants exhibited a range of binding affinities, with some showing affinities similar to human FH, while others had significantly lower affinities.

Conclusions:

• Rhesus macaques possess at least three allelic variants of FH that influence binding to FHbp.
• FH binding to FHbp-containing vaccines can modulate protective antibody responses.
• Understanding macaque FH binding characteristics is essential for selecting appropriate animal models to study FHbp vaccine immunogenicity.