The Immunological Study Of HPV16L1Esophageal Cancer Vaccines

There are over300thousand patients died of esophageal cancer worldwide everyyear. In our country, the morbidity of esophageal rank first in the world,approximately150thousand patients died per year. Investigation data showesophageal cancer may be caused by multifactorial synergy, including chemicalfactors, environmental factors, biological factors, genetic factors and the unhealthyliving habits. Accumulating evidence shows that HPV is tightly associated withesophageal cancer, and considered as an important pathogenic factor of this disease.For this reason, anti-HPV vaccines could also be effectively prophylactic andtherapeutic agents for esophageal cancer.HPV vaccines are classified to either prophylactic vaccines or therapeuticvaccines. Prophylactic vaccines based on HPV L1VLPs can induce neutralizingantibodies, providing100%protective effect only for corresponding types of HPVs,while immunity for other HPVs is poor. Furthermore, prophylactic vaccines cannotclear the infected cells and have no curative effect. Therapeutic vaccines, in contrast,can only eliminate the infected cells and HPV-related tumors by inducing specificcellular immunological responses. At present, the target proteins are focused on E6/E7,but E6and E7, as oncogenes, have potential carcinogenic risk. Althoughtransformation activity can be removed by the gene mutation, the safety is not ideal.Further, the immunogenicity of mutant E6/E7is much lower than their wild-typecounterparts. Previous studies by our group detected the expression of L1inesophageal cancer tissues and isolated cell lines. This finding provided the rational fordeveloping therapeutic HPV L1vaccines. Due to the potent immunogenicity andhighly safe, HPV L1is considered as an ideal target protein for novel HPVtherapeutic vaccines.In this study, the recombinant DNA, adenovirus and adeno-associated virusvaccines containing codon-modified HPV L1gene were constructed, and mouseswere inoculated with the vaccines by repeat and sequential immunization regime. Thespecific humoral and cellular immunity was evaluated by pseudovirus neutralizationassay and ELISPOT respectively. The results indicated that recombinantadeno-associated virus, adenovirus and DNA vaccines can induce specific humoraland cellular immune response in a short time and11weeks after the lastimmunization, specific immune responses were undetectable. Comparing withordinary injection, gene transfer can further enhance the cellular immunity ofrecombinant DNA vaccine by5times. Combined immunization of mice with thesevaccines by repeat and sequential regime can induce more potent and sustainedspecific humoral and cellular immunities. After the booster immunization the immune response was decreased, but in the later phase of immunization, the decrease rate wasslow, the protective efficacy can be maintained for a long period of time. It shows thesequential repeat immunization strategy is effective.