HPV L2 cross-protective vaccines

Infections with human papilloma viruses present one of the main risk factors for the development of invasive cervix carcinoma. Two commercially available vaccines, Gardasil® and Cervarix®, based on so called virus-like-particles (VLPs) are able to induce neutralizing anti-L1 antibodies and are protective against infection by the two high risk HPV types 16 and 18. However, the vaccine induced anti-L1 antibodies are highly HPV type specific (for HPV 16 and 18) and do not effectively protect against other oncogenic HPVs. At least 15 HPV types have been causally linked to cervix carcinoma, and thus a broadly cross-neutralizing vaccine is desired. Interestingly, it has been found that antibodies against the HPV minor capsid protein L2 act cross-neutralizing against several HPV types. However, L2 suffers from a rather low immunogenicity compared to the more immunogenic L1. In collaboration with the University of Parma, vaccine antigens in which neutralizing L2 epitopes are inserted into the scaffold of bacterial thioredoxin were developed. These antigens are able to induce neutralizing responses much more efficiently compared to the L2 protein alone. It is the objective of the project to further improve antigen design, to investigate alternative scaffolds and to determine mechanisms of neutralization. Screening for optimized, immunogenic L2 epitope conformations will be performed using highly efficient and broadly cross-neutralizing L2 monoclonal antibodies.