Structure-based design of chimeric antigens for multivalent protein vaccines

Area of Science:

• Vaccinology
• Bacteriology
• Structural Biology

Background:

• Pathogenic bacteria pose significant public health threats, necessitating novel vaccine development strategies.
• Antigenic diversity and challenges in manufacturing membrane proteins hinder effective vaccine design.
• Serogroup B Neisseria meningitidis (MenB) is a leading cause of bacterial meningitis, particularly in developed nations.

Purpose of the Study:

• To develop a structure-based design approach for creating chimeric antigens (ChAs) for subunit vaccines.
• To generate ChAs targeting MenB using factor H binding protein (fHbp) as a scaffold for the PorA VR2 epitope.
• To evaluate the immunogenicity and protective efficacy of MenB ChAs.

Main Methods:

• Structure-based design was employed to create chimeric antigens (ChAs).
• ChAs were engineered using the fHbp scaffold to display the immunogenic PorA VR2 epitope.
• Structural analyses confirmed the correct folding of fHbp and the immunogenic conformation of the PorA VR2 epitope.
• Immunization studies in mice were conducted using the developed ChAs.

Main Results:

• Structural analyses confirmed the integrity of the chimeric antigen structure.
• Immunization with MenB ChAs elicited antibodies against both fHbp and PorA.
• Generated antibodies recognized antigens on clinical MenB isolates.
• Antibody responses correlated with protection against meningococcal disease in murine models.

Conclusions:

• Chimeric antigens (ChAs) represent a promising strategy for developing subunit vaccines against pathogenic bacteria.
• This structure-based design approach can overcome challenges posed by antigenic diversity and membrane protein manufacturing.
• ChAs offer a versatile platform for creating multivalent vaccines tailored to specific pathogens like MenB.