HIV-Env gene DNA allosteric recombinant envelope protein antigen immune response anti HIV experiment and method

Abstract

This invention is called: the experiment and method of the protein envelope which is allosteric restructuring of the HIV-Env gene DNA and its antigenic immunity responsive HIV. It relates to the domain of life sciences and medicine sciences. It is confirmed that gp120 of the HIV protein envelope or the gp160 of the antigenic vaccine combines with cell CD4+ that can induce the infirm immunogen of the alloantigen of the immune tolerant receptor CD4 and can not induce the HIV to infect the immune response of the parasitifer. It can also eliminate the multi-clone group of hill of the wild virus which is of fast copy the initial infection virus, high variability and sequence diversity. This invention can develop the non-spark human tolerant immunity HIV vaccine of the protein envelope which is allosteric restructuring of the HIV-Env gene DNA, the HIV preventive vaccine that can provide the scientific basis of the direct animal experiment and direct clinical trial of human being. It also provides the enforceable anti-HIV cell model, rodent model, non-human Primates model and the research program of human clinical trial.

Description

technical field [0001] The invention relates to an HIV-Env gene DNA allosteric recombinant envelope protein antigen immune response experiment and method for anti-HIV. It involves the field of life sciences, and the field of medicine. Revealing that HIV envelope protein gp120 or gp160 antigen-vaccine is associated with CD4 + Binds to cellular CD4 receptors and induces immune tolerance to CD4 receptors Heterologous ligand antigens Weak immunogen, induces immune tolerance of HIV-infected hosts, Humoral immune responses are slow to produce protective antibodies, lag behind virus mutation, and cannot induce HIV-infected host immune responses , effectively remove the wild virus polyclonal strain group with fast replication speed, high variability and high viral sequence diversity of the original infected original virus. It can develop HIV-Env gene DNA allosteric recombinant envelope protein antigen HIV therapeutic vaccines and HIV prevention vaccines that do not trigger human imm...

AI Technical Summary

Problems solved by technology

3. There is no surrogate end point for HIV vaccine clinical trials that can evaluate and verify the effective protection rate of candidate HIV vaccines in a short period of time; there is no such thing as evaluating and screening out one of the hundreds of candidate HIV vaccines that has entered clinical research. Ability to Apply Valuable HIV Vaccines

Even if modern HIV scientific research has enough scientific research resources, scientific research funds, scientific research personnel, and scientific research time, it can recruit enough people from the society to conduct phase III / IV clinical human trials of a candidate HIV vaccine. 1 million HIV-negative high-risk volunteers; because it is impossible to avoid the development of new synthetic HIV vaccines, there are huge unknown scientific research risk variables in the implementation of Phase III / IV clinical human trials, and there is no possibility of passing Phase III / IV clinical human trials. Among the hundreds of candidate HIV vaccines that can enter clinical research, evaluate the ability to screen out one HIV vaccine with practical application value

[0006] To sum up, there are obvious flaws and deficiencies in modern HIV basic science research and experimental biology, which are simple and scientific in terms of thinking, methodology, and methods; confining and restricting modern HIV scientific research cannot solve the problem of HIV infection-AIDS AIDS! The inventor believes that: modern HIV scientific research must be like the implementation of the Human Genome Project, to establish large storage samples of HIV viruses from different sources of different individuals in the initial HIV-infected population plasma, PBMC cell bank: collect and store various samples of different individuals in the initial HIV-infected population Plasma and PBMC cells from large samples of HIV viruses of different origins, revealing the different individuals of the initial HIV-infected population, the polyclonal strains of various subtypes of wild HIV viruses of different origins, and the HIV virus gene-cDNA sequence type; using the initial HIV-infected population Plasma, PBMC cell bank, all kinds of different gene sequence type isotopic HIV immunogen-recombinant HIV immunogen, immunization of sterile GF mice to obtain various gene sequence types Isotopic HIV immunogen, each isotopic epitope-specific B cells, established by hybridoma technology, a variety of different gene sequence type isotope HIV immunogen each isotopic epitope monoclonal antibody specific library: revealing the initial HIV infection Different populations, different subtypes, different sources of wild HIV virus polyclonal strains, various gene sequence types, isotopic HIV immunogens, and each isotopic epitope clonal specific type; use the initial HIV infection population of different individuals Plasma, PBMC cell bank of large storage specimens of various HIV viruses from different sources, various gene sequence type isotopic HIV immunogens-genetic recombinant HIV immunogens, immune rodents mice or rats or guinea pigs or rabbits or non-human Primate monkey or gorilla anti-HIV animal model, obtain animal serum against various gene sequence type isotope HIV immunogen neutralizing antibodies; apply animal serum containing neutralizing antibodies, respectively, and perform in vitro culture obtained from the original HIV Large-scale storage samples of HIV viruses of different origins from different individuals in the infected population, plasma, PBMC cell bank, various wild HIV virus polyclonal strains of different origins of plasma, and PBMC cells infected with normal human PBMC cell model experiments to establish inhibition of different origins of wild HIV viruses Infected normal human PBMC cell model library: screening and looking for the effective protection rate of wild virus polyclonal strains that can induce the immune response of the initial HIV-infected population and effectively eliminate the initial infection provirus replication speed, high variability, and high viral sequence diversity High, each subtype of HIV protective immunogen - strong immunogen, cross-subtype HIV protective immunogen - strong immunogen; each isotopic epitope monoclonal of different gene sequence type isotopic HIV immunogens Antibody-specific type library, select isotopic HIV protective immunogen, each isotopic epitope clone specific type, various gene sequence type isotopic HIV protective immunogen, guide the design and application of 2 or 2 types One or more of the above different HIV protective immunogens of the same subtype or different subtypes, each isotopic epitope clone specific type of different HIV protective immunogens, combined with various candidate new mixed HIV protective immunogens Immunogen-vaccine: Infect normal human PBMC cell model library with different sources of wild HIV virus, screen out the immune response that can induce the initial HIV-infected population, and effectively eliminate the initial infection of the original virus with fast replication speed, high variability, and diverse viral sequences The highly effective protection rate of the wild virus polyclonal strain group is high, each subtype mixed HIV protective strong immunogen antigen-vaccine, and cross-subtype mixed HIV protective strong immunogen antigen-vaccine, it has been proved that it can be used as a vaccine. Implement clinical human experiments on HIV therapeutic vaccines and HIV preventive vaccines; input the detailed experimental process and data records into the corresponding computer comprehensive analysis system to build a comprehensive biological science research experiment platform that avoids the huge unknown scientific research risk variables in the development of synthetic HIV vaccines