The Study Of Novel Cervical Cancer Prophylactic Vaccines Based On HPV16L2

Cervical cancer is the second leading cancer among women, trailing only breast cancer in incidence. Currently, the expensive surgical procedure and chemoradiotherapy are the primary clinical measurements for cervical cancer according to the phase of the disease. However, the bulk of patients still suffer a relapse leading to eventually mortality. Extensive body of evidence established the link between the high-risk types of Human papillomavirus (HPV) and cervical cancer. Some types of HPVs are considered as the major etiological agents of the disease.Therefore, using the vaccine to prevent HPV infections would be a more cost-effective strategy to reduce the incidence of cervical cancer.Two prophylactic HPV vaccines based on HPV L1Virus-Like Particles(VLPs) have been licensed recently and can effectively protect against the infections of related types of HPVs. However, the protection effects of L1vaccines have virus-types specifics and can not neutralize non-cognate HPV types. While, to broaden the spectrum of protection by adding valences would increase the risk of occurring undesirable side-effects. Current evidences have shown that HPV minor capsid L2N terminal region contains conserved common epitopes capable of inducing cross-neutralizing antibodies against various non-cognate pseudovirions. However, its lower immunogenicity limits the further application.In this study, we constructed a series of recombinant peptide vaccines with PTD fusing or mixing with L2N terminal peptides and recombinant adenovirus vaccines which contain HPV16L2N terminal sequence or full-length gene.Then the humoral and celluar immunity are systematically evaluated.The experimental results:(1) Indirect ELISA assays shew that the recombinant peptide vaccines could induce specific antibodies and antibodies levels were positively correlated with peptides’size.(2) The pseudovirus neutralization assays indicated that PTD fused with L2peptides induced high-titer of cross-neutralizing antibodies,and considerably increased the proportion of the neutralizing antibodies in the specific total antibodies.(3)The rAd5-HPV16L2recombinant adenovirus could induce special cross-neutralizing antibodies and strong HPV16L2specific cellular immune response.In summary, PTD fused with L2N terminal peptides can considerably improve their immunogenicity,and its humoral enhanced effect was positively correlated with peptides’size.The rAd5-HPV16L2recombinant adenovirus could induce strong HPV16L2specific cellular immune response. Combined immunization using the two types of vaccines would elicit better protective effects.