Structure-based design of chimeric antigens for multivalent protein vaccines

Structure-based design of chimeric antigens for multivalent protein vaccines

Vaccines against bacterial pathogens, mostly based on the pathogens’ toxins or capsules components, have been revolutionary for human kind. However, these approaches are not feasible for pathogens such as serogroup B Neisseria meningitidis – where vaccine development has been impeded by pathogen diversity, the inability to use capsule-based vaccines and technical difficulties of generating antigens from membrane-embedded proteins. A solution for this problem is critical due to the rise of multi-drug resistant bacteria.

Hollingshead and colleagues have begun to address this problem by engineering chimeric antigens (ChA) consisting of two different N. meningitidis proteins. ChAs contain the protein fHbp as a molecular scaffold on to which they have engineered a critical region, the VR2 loop, from the membrane-bound protein PorA. They found that the ChAs retain the architecture of fHbp and the VR2 loop. The ChAs were also able to successfully elicit protective immune responses in mice against both protein antigens.

This proof-in-principle study demonstrates that ChAs can present important parts of membrane-bound proteins to the immune system and initiate an immune response, opening the door to a new generation of multivalent vaccines.

 

Lisa Gartenmann

Hollingshead S, Jongerius I, Exley RM, Johnson S, Lea SM and Tang CM (2018).

Nat. Commun. 13;9(1):1051.