Recombinant Human Papilloma Virus type 56 L1 protein (VLP)

Human Papillomavirus (HPV) is a double stranded DNA virus. It is commonly spread among humans and primates. Research on its structure shows that HPV is a spherical virus with a diameter of about 50-60nm and consists of a shell and a core. According to the early and late sequence of HPV gene expression, it can be divided into early region (E), late region (L) and long control region. The core of HPV is composed of a circular DNA molecule, which encodes 8 genes, namely E1, E2, E4, E5, E6, E7, L1 and L2. Studies have found that these genes play different roles in HPV infection. Among them, the E6 and E7 genes have attracted much attention because they can interfere with the normal growth and apoptosis of cells, causing abnormal cell proliferation and inducing the occurrence of cancer. Through step-by-step in-depth research, at least 200 HPV subtypes have been discovered, of which about 40 can infect the genitals and anal areas of humans. According to the potential of HPV to induce cancer, they are usually divided into high-risk and low-risk types in clinical practice. High-risk HPV subtypes include 16, 18, 26, 31, 33, 35, 39, 45, 51, 52, 53, 56, 58, 59, 66 and 68. These subtypes can cause precancerous lesions or cancer. Low-risk HPV subtypes include 6, 11, 40, 42, 43, 44, 55, 61, 81 and 83, which can cause benign diseases such as skin warts, genital warts and recurrent respiratory papilloma.

Figure 1. Genome organization of human papillomavirus. (Sources: Nick A Antonishyn, et al. 2007)

At present, there is no specific drug that can directly eliminate HPV in clinical practice. For infected people, the response of their own immune system is the most effective means to fight the virus. Therefore, HPV vaccination is the most economical and effective preventive measure to prevent HPV infection and related diseases. At present, among the HPV vaccines on the market, the bivalent vaccine can prevent HPV16 and HPV18, and can reduce the incidence of cervical cancer by 70% after vaccination; the quadrivalent vaccine prevents HPV16, HPV18, HPV6 and HPV11 genotypes. After vaccination, in addition to reducing the incidence of cervical cancer, it can also prevent 90% of genital warts. The nine-valent vaccine can not only prevent HPV16, HPV18, HPV6, and HPV11 genotypes, but also add HPV31, HPV33, HPV45, HPV52 and HPV58, a total of nine genotypes. After vaccination, it can reduce the incidence of cervical cancer by 90%, and also prevent 90% of genital warts.

HPV vaccines use virus-like particles formed by the assembly of HPV capsid proteins L1 and L2 as antigens to activate the humoral immune system to produce specific neutralizing antibodies, thereby preventing HPV infection. Due to its good safety, it has been widely used, but it has no obvious therapeutic effect on HPV infection and related lesions. At present, HPV vaccines used in clinical practice are all for the purpose of prevention by producing neutralizing antibodies. Some studies are also based on mediated cell immunity and used as therapeutic HPV vaccines. Most therapeutic HPV vaccines developed to date target E6 and E7 viral proteins. The DNA sequences encoding E6 and E7 fusion proteins are inserted into the vector, and mutations are introduced into the regions responsible for the interaction between E6 and p53 and the interaction between E7 and retinoblastoma protein (pRb) to reduce their carcinogenicity. In addition, E1 and E2 viral proteins are highly expressed before viral genome integration and are also strong candidate target antigens for therapeutic vaccines. Therapeutic HPV vaccines mainly include vector vaccines, subunit vaccines, nucleic acid vaccines and cell vaccines. In recent years, a large number of studies on therapeutic HPV vaccines have shown good results, and some have entered the clinical trial stage, but no therapeutic HPV vaccine has been approved for human use.

HPV
Papillomavirus
Human wart virus
Genital wart virus
Cervical cancer virus