Research On HPV18L1Vaccines Against Esophageal Cancer

Esophageal cancer is one of the six most common cancers, China is one ofregions of high incidence of esophageal cancer. Generally, the esophageal cancer isthe result of a long-term synergic effects of various factors (including environmental,lifestyle, genetics, etc.), but the exact etiopathogenisis is unknown. In the1980s,Syrjane proposed the morphological correlation between HPV infection tissuespecimens and esophageal squamous cell carcinoma. A mass of subsequent studieshave shown that HPV genomic fragments can be detected in esophageal tissue,however, there is a huge differences in HPV detection rate ranging from0to100%.This may derive from the differences in the sample collection methods, sample size.Molecular epidemiology researches conducted by our group in Shantou, Jieyang andother areas indicate that50%to80%of the esophageal cancer tissues specimens andcell lines have been detected with HPV virus, wherein HPV16and18reach to about60%; HPV18E6/E7can induce immortalization of normal human fetal esophagealepithelial cell and a variety of tumor promoters(TPA and butyric acid), chemicalcarcinogens (nitroso pyridine), arsenic trioxide and radiation etc. can accelerate thecarcinogenesis induced by HPV E6E7, which further suggests, esophageal cancer isthe results of multifactorial synergistic effects. In summary, although the incidenceof esophageal cancer is the results of multifactorial long-term synergistic effects, butthe high-risk HPV is an important virological cause of esophageal cancer. Therefore,the development of a vaccine against HPV could also prevent and treat esophagealcancer.This study designed a novel vaccine against HPV18based on DNA/rADV,proposed a multi-carrier sequential repeated immunization methods, and studied thesequential repeated immunization strategies of DNA and recombinant adenovirus todetermine the optimal immunization procedures. The results showed that therecombinant DNA vaccine VR-HPV18L1and recombinant adenovirus vaccinerAdv-HPV18L1using prime-boost-boost sequential repetition combined inoculationimmunization strategy can induce strong and long-lasting humoral and cellularimmune responses, although the cellular immune response in strengthening afterimmunization will gradually decline, but in the latter part of the immunization course,the rate of decline slowed significantly compared with pre-immunization, and the co-immunization of the mixture of HPV16and18can further enhance the immuneresponse against HPV18-specific immunity. In addition, the subject also constructedthe recombinant adeno-associated virus vector rAAV2/1-HPV18L1, and studied theimmune effects of the viral vector with a single vaccination. Experimental resultsshow that a single intramuscular injection of rAAV2/1-HPV18L1can induce hightiters of serum antibodies and HPV18L1-specific cellular immune response.Considering all these experimental results, we will study the protective effects ofthe three vaccines using a multi-carrier sequential repeated immunization strategy forthe experimental basis of the further development of esophageal cancer vaccine.