Rational design of a meningococcal antigen inducing broad protective immunity

Area of Science:

• Microbiology
• Immunology
• Vaccine Development

Background:

• Sequence variability in protective antigens poses a significant hurdle for vaccine design.
• Neisseria meningitidis factor H binding protein (fHBP) exhibits over 300 variations across three non-cross-protective antigenic groups.

Purpose of the Study:

• To develop a single antigen capable of inducing protective immunity against all known sequence variants of N. meningitidis fHBP.
• To overcome the challenge of sequence variability in developing broadly protective meningococcal vaccines.

Main Methods:

• Rational design, expression, and purification of 54 fHBP mutants.
• Testing mutant efficacy in mice for induction of protective immunity.
• Structural determination of a lead chimeric antigen using X-ray crystallography.

Main Results:

• Identification of a lead chimeric fHBP antigen.
• The chimeric antigen induced high levels of cross-protective antibodies in mice against all tested N. meningitidis variant strains.
• The antigen features a conserved core with engineered surfaces targeting all three variant groups.

Conclusions:

• Structure-based design enables the creation of single antigens with multiple immunodominant surfaces.
• This approach is effective for developing broadly protective vaccines against highly variable pathogens like N. meningitidis.