Abstract
Excerpt: Vaccines train the immune system to recognize antigens, preventing disease by enabling a timely adaptive immune response. Vaccine efficacy and safety may depend on directing the antibodies to specific epitopes, especially if the antigenic target protein is immunologically “self”, such as a cancer cell or a sperm cell. Short peptides can focus antibodies to the desired epitopes, but such small antigens are unstable unless incorporated into a larger protein. We selected human papillomavirus (HPV) L1 protein as a carrier for a novel peptide subunit vaccine, constructed by inserting the coding sequences of the desired epitopes into sites of natural variation in the L1 proteins of the many HPV strains. The native conformation of these epitopes, based on molecular models, is preserved by disulfide linking its endpoints, an act which may also help to preserve the folding pathway of L1. Successful raising of antibodies that bind the target is seen as an indicator of successful native-state antigenic loop modeling. Successful self-assembly into 55 nm virus like particles (VLPs) is an indicator that the inserted loops do not interfere with folding and assembly of the L1 protein. Previous work has shown that VLPs are especially immunogenic scaffolds, and that the polyvalency possible in VLP display of peptide antigens sometimes improves the immune response. This work focuses on the design and testing of VLPs displaying peptides from a sperm specific calcium channel, CatSper, to produce an anti-sperm vaccine for contraceptive use. We will discuss the folding and assembly of the designed chimeric capsid proteins.
