The Nat Comm-Channing team published the results of the new multivalent cervical cancer vaccine.

Persistent infection of human papillomavirus (HPV) can lead to proliferative lesions of epithelial tissues and a variety of benign and malignant tumors.more than 200 types of HPV have been identified, of which at least 25 high-risk types are highly associated with cervical cancer.in the world, cervical cancer is the third largest malignant tumor in women, with 569000 new cases and 311000 deaths every year, which seriously threatens women's health.HPV vaccination is an effective means to prevent cervical cancer.HPV L1 protein can self assemble into virus like particles (VLP) in vitro, which has strong immunogenicity and is the main form of HPV vaccine immunogen.due to the strict type restricted immune protection induced by HPV VLP, it is difficult to produce cross protection. Therefore, HPV vaccine can prevent different types of infection by mixing multiple VLPs.at present, there are bivalent, tetravalent and 9valent HPV vaccines on the market. It is of great significance to develop HPV vaccines with higher protection range for better prevention of cervical cancer and prevention of HPV transmission in the population.recently, Professor Xia Ningshao of Xiamen University published a research paper entitled "rational design of a multi value human papillomavirus vaccine by capper hybrid co assembly of virus like particles" online on nature communications.based on the deep understanding of the assembly mechanism of HPV VLP, a hybrid virus like particle (capsomere hybrid) was designed, which could simultaneously produce immune protection against multiple types of HPV VLP, chvlp) laid a key technical foundation for the development of a new generation of multivalent cervical cancer vaccine covering all high-risk types of HPV, and provided new ideas for the design of other highly variable virus vaccines and vaccines targeting new tumor antigens.in this study, HPV Cysteine at position 175 and 428, which are critical for VLP assembly, were mutated to alanine (c175a and c428a), respectively. The results showed that the L1 pentamer could not be assembled to form VLP, but two different types of l1-c175a pentamer and l1-c428a pentamer could hybridize to form a single hybrid virus like particle (chvlp), and the optimal stoichiometric ratio of heterozygous assembly was 1:1 The results of freeze electron microscopy showed that the particle morphology of chvlp was similar to that of wild-type VLP, both of them were icosahedral symmetry structure with T = 7. Interestingly, the hybrid assembly method was a random assembly of HPV types. 2-9 different types of L1 pentamers could be hybridized to form chvlp. In theory, one chvlp could accommodate 72 different types of L1 pentamers.using monoclonal antibodies to analyze the antigenicity of particles, it was found that chvlp not only retained most of the type specific epitopes, but also produced new epitopes different from the wild type.furthermore, the L1 pentamers of 9 types (HPV 6, 11, 16, 18, 31, 33, 45, 52, 58) were assembled into a single particle to form a Nona type chvlp. Gardasil could be induced in mouse model 9? Is equivalent to the high and high titer of nine types of antibodies, and has some advantages in vaccine preparation methods: the pentamer state is more stable in the purification process, the particle assembly process is more controllable, and there is no need to add reducing agents (such as DTT), and the vaccine preparation process of a single particle.the researchers proposed that if the hybrid assembly strategy was combined with the tri type chimeric VLP, the pan HPV broad-spectrum vaccine could be made by clustering 216 types of HPV neutralizing epitopes on a single chvlp, covering more than 200 types of HPV currently identified.this method is expected to be applied to the design of vaccine and controllable drug delivery vector for hypervariable pathogens and tumor cells carrying variable new antigens.the complementary assembly design of viral like particles based on pentamer hybrid and the immune protection effect of heterozygous nine valent HPV vaccine, Professor Xia Ningshao of Xiamen University has carried out a series of work in the application and basic research of HPV preventive vaccine for a long time: the preparation of HPV based on E.coli was clarified VLP assembly mechanism (structure, 2016); revealed the structural basis of antibody mediated HPV type specific neutralization (mbio, 2017); developed the first domestic first generation cervical cancer vaccine (HPV 16 / 18 bivalent, Xinkening? Cecolin?; hum vacc & amp; on the market in China; Immunother, 2014; vaccine, 2015; vaccine, 2017; SCI China Life SCI, 2019; JNCI, 2020); the second generation of cervical cancer vaccine is about to carry out phase III clinical trial (HPV, 9-valent; emerging microbes & amp; Based on the structural vaccinology design, it "takes the lead in the development of the third generation cervical cancer vaccine" (HPV 20 price; NAT commun, 2018).the published research work is a new multivalent HPV vaccine design based on the in-depth understanding of HPV VLP assembly mechanism.Professor Li Shaowei, Associate Professor Gu Ying and Professor Xia Ningshao of Xiamen University are the co authors of this paper. postdoctoral students Wang Daning, doctoral students Liu Xinlin and Wei Minxi of Xiamen University are the co first authors of this paper. original link: plate maker: old wings