HPV is a double-stranded circular DNA virus belonging to the papovaviridae family, which mainly infects the epithelial tissues of the skin and mucous membranes. HPV was first discovered in humans in 1933, and the first case of genital HPV was identified in 1978. Human papillomavirus (HPV) is the main cause of cervical cancer that is Cervical screening can reduce the risk of cervical cancer but cannot prevent HPV infection. The advent of preventive HPV vaccines has significantly reduced the incidence of cervical cancer worldwide, but therapeutic HPV vaccines are still in the experimental stage. There are more than 100 subtypes of HPV, and at least 40 of them can infect the genital area. Most people infected with HPV have no obvious clinical symptoms, the body can clear it by itself, and it is not easy to be recognized. The main route of transmission of HPV is sexual contact, through infection of damaged epithelium. According to the degree of harm caused by HPV infection, it is divided into high-risk and low-risk types. Low-risk types mainly include HPV6, 11, 42, etc., which can cause genital warts and recurrent respiratory papillomatosis (RRP), but rarely cause cancer. The identified high-risk types include HPV16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, and 59. Persistent infection of high-risk HPV is the main cause of cervical cancer, which is the fourth popular cancer among female malignant tumors in the world. HPV16 and 18 are the strongest carcinogenic genotype, causing 70 percent of cervical cancers.
HPV vaccine occupies an important position in the prevention and treatment of cervical cancer in the world. It can protect at least 80% of the target population. So far, more than 80 countries have included the HPV vaccine into their national immunization plans. HPV vaccines are divided into preventive HPV vaccines and therapeutic HPV vaccines.
The preventive HPV vaccine is the first vaccine developed by humans to prevent malignant tumors. Its mechanism of action is to use the L1 capsid protein of HPV virus to induce the production of virus-like particles (VLPs), which are assembled in different carriers, such as yeast, to stimulate humoral immunity of the human body and produce specific antibodies. The titer of the antibodies can be increased by more than 10 times. Thus, vaccine recipients can acquire immunity against corresponding subtypes of HPV. The L1 capsid protein is only expressed on the surface of epithelial cells that do not release VLPs, and therefore has no therapeutic significance for pre-existing infections or lesions. There are currently three types of preventive HPV vaccines that have been marketed in the world: bivalent vaccine Cervarix for high-risk subtypes HPV16 and HPV18, quadrivalent vaccine Gardasil4 for high-risk subtypes HPV16, HPV18 and low-risk subtypes HPV6, HPV11, and nine-valent vaccine Gardasil9 for high-risk subtypes HPV16, HPV18, HPV31, HPV33, HPV45, HPV52, HPV58 and low-risk subtypes HPV6, HPV11.
Therapeutic HPV vaccine is mainly suitable for patients who have already developed cervical cancer or precancerous lesions. It can prevent the lesions from getting worse and can effectively eliminate tumor cells and infected cells. Different from the preventive HPV vaccine, the principle of the therapeutic HPV vaccine is redesigning the protein of the natural structure of the HPV virus to obtain a new antigen with a similar but different structure. The current therapeutic HPV vaccine targets the specific antigen. The main genes are E6, E7, E2, and E5. The therapeutic HPV vaccine presents antigens to antigen-presenting cells, activates the immune response of CD8+ or CD4+ cells, and targets and kills HPV-infected cells and cancer cells expressing E6 and E7, thereby treating cervical cancer. cancer. There are many types of therapeutic HPV vaccines currently known, which can be divided into: nucleic acid vaccines, polypeptide vaccines, bacterial vector vaccines, viral vector vaccines, cell vaccines, etc. The research and development of therapeutic HPV vaccines is far more complicated and difficult than preventive HPV vaccines. Although therapeutic HPV vaccines have made some progress in the past few years, most of them are in the stage of animal trials or Phase I and Phase II clinical trials, and many problems remain to be resolved.
Creative Diagnostics provide the pseudotyped GFP HPV which is generated on 293FT cell line and stalely expressed codon-modified papillomavirus capsid genes, L1 and L2. With the GFP signal of each pseudovirions, it is easy to process mid-scale and large-scale screening test of anti-HPV candidates.
Creative Diagnostics has launched a full series of HPV pseudovirion-based neutralization assay (PBNA) for measuring neutralizing anti-HPV antibodies. Two assays available to measure 9-valent HPV neutralizing antibodies qualitatively and quantitatively.