Deep interpretation! The current situation and progress of the research on the new coronavirus vaccine!

!--webeditor:page title"--July 29, 2020 /PRNewswire/ -- According to THE latest real-time WHO statistics, as of 17:06 BST on July 24, the total number of confirmed cases of new crown pneumonia worldwide has increased to 15257287, with a cumulative death of 628,240The global record-breaking global new crown outbreak bodes well for the natural retreat of the epidemic, and the continued deterioration of the global new crown outbreak means that the concept of "group immunization" proposed by some Western countries is completely bankrupt, and the development of vaccines is expected to be the ultimate weapon to end the new crown pneumonia epidemic has become the consensus of all countries around the worldPhoto Credit: Institute for Research on Public Policy Currently, SARS-CoV-2 poses a serious threat to human health, socio-economic development, and global medical and public health systems, and current clinical treatment is primarily supportive of diseaseSARS-CoV-2 will enter the body through glycoprotein recognition, when the vaccine acts on the body, can induce the body to produce targeted glycoprotein neutralizing antibodies, blocking the virus into host cellsTherefore, it is critical to develop a specific vaccine that is safe and effective and can be quickly delivered in the populationPreviously, SARS-CoV and MERS-CoV have been designed for a variety of vaccines, including inactivated viral vaccines, DNA vaccines and vector vaccines, which are not available, but can provide some experience in the development and design of SARS-CoV-2 vaccinesSince the COVID-19 outbreak, scientists in China have advanced the design and development of SARS-CoV-2 vaccines from five technical directions: inactivated virus vaccine, detoxification vaccine, recombinant protein vaccine, nucleic acid vaccine, and adenovirus vector vaccineFor the research and development of the five major vaccines, domestic researchers have carried out preclinical research and launched the corresponding clinical trialsOn June 20, 2020, the new coronavirus inactivated vaccine independently developed by the Institute of Medical Biology of the Chinese Academy of Medical Sciences entered Phase II clinical trialinats in Red River State, Yunnan Province; The AZD122 vaccine developed by The University of Oxford in collaboration with AstraZeneca Pharmaceuticals has entered Phase III clinical trials, and a vaccine called mRNA1273 developed by The American biopharmaceutical company Moderna is also about to enter Phase III clinical trials1, inactivated vaccine inactivated virus vaccine in the development process to ensure that the virus de-infective without loss of its immunogenicity, this technology is easy to achieve and body fluid immune response effect is good, so inactivated virus vaccine has now become the preferred form of vaccine for new infectious diseasesAt present, four SARS-CoV-2 inactivated vaccines from China have been approved for clinical trials, and the research and development units are the Wuhan Biological Products Research Institute of The Central Health Group (Wuhan Biology), the Beijing Kexing Zhongwei Biotechnology Company (Beijing Kexing), the Beijing Biological Products Research Institute of the Chinese Central Group (Beijing Biology), and the Institute of Medical Biology of the Chinese Academy of Medical Sciences (Medical Biology Institute)Another six inactivated vaccines are in the preclinical research phase, with research and development units being Beijing Kexing/Dynavax, Valneva/Dynavax, Institute of Medical Biology, Osaka University, Osaka University, Kazakhstan Biosecurity Research Institute, and Beijing Minhai Biotech Co., LtdChina has a wealth of experience in the research of inactivated virus vaccines, on April 14, 2020, the State Drug Administration through two inactivated SARS-CoV-2 vaccine I and Phase II joint clinical trialapplicationapplications, and simultaneous start of relevant clinical trials, these two types of inactivated new crown virus vaccines are developed by the State Pharmaceutical Group China Biological Wuhan Biological Products Research Institute Co., Ltd., Beijing Kexing Zhongwei Biotechnology Co., LtdThe SARS-CoV-2 inactivated vaccine, which has been approved for clinical studies, has been the result of the new crown virus inactivated vaccine I/II clinical trial developed by Wuhan Institute of Biological Products, and the results of the phase I/II clinical trial show that all the subjects have produced antibodies; On May 6, 2020, the Qinchuan team of the Institute of Medical Experimental Animals of the Chinese Academy of Medical Sciences and others developed a purified inactivated new coronavirus candidate vaccine, which can induce specific SARS-CoV-2 neutralization antibodies in mice, rats and rhesus monkeys, which can effectively neutralize 10 representative SARS-CoV-2 strains, indicating that they may have a wide range of antibody-CoV-2Further tests of rhesus monkey stoicism have shown that it can be partially protective when given a dose of 3?g, and when vaccinated at 6 ?g, it can play a complete protective effect without any enhancement of antibody dependenceThrough clinical signage, hematology and histopathological analysis of rhesus monkeys, it is shown that the inactivated vaccine is safe and reliablePhoto Source: PRESSENZA2, Detoxivisive Live Vaccine is a class of pathogens after artificial treatment, so that the virus lost pathogenicity, but retains the original proliferism and immunogenicity, its immune time in the body for a long time, and can induce systemic immunity and mucosal immune response At present, there are a number of live vaccines for detoxification, such as yellow fever, smallpox, measles, mumps, rubella, chickenpox and other anti-virus live vaccine, and the current domestic research on SARS-CoV-2 anti-virus vaccine progress is relatively slow 3 Recombinant protein vaccine recombinant protein vaccine is considered to be the safest vaccine, it is the target antigen gene of the virus integrated into the expression vector, and then the expression vector into bacteria, yeast, mammalian or insect cells, after induction to express a large number of antigen protein, and then through purification of the vaccine At present, the Institute of Microbiology of the Chinese Academy of Sciences has completed the vaccine design, and in animals, after the completion of the test, also need to detect the effect of immunization and safety evaluation; Adjormtos of akeratose, such as MF59, AS03, AF03, can effectively induce recombinant protein vaccine's body fluid immunity and cell immunity, and can induce a wider range of cross-reactions, so it may be more suitable for the development of SARS-CoV-2 recombinant protein vaccine !--/ewebeditor: !--webeditor: !--.) The methods such as bombblasting are introduced into the host body to express antigen protein in the host body, thus inducing the host cell to produce the immune effect of the antigen protein in order to achieve the goal of preventing and treating diseases; 4.1 DNA Vaccine DNA Vaccine is the introduction of the external gene of the target antigen into animal cells, so that the exogenous gene is expressed in its living body, the resulting antigen induces the body to produce a specific body fluid immune and cellular immune response, in May 2020, published in the journal Nature Communications, researchers of INOVIO published its SARS The preclinical data of -CoV-2's DNA vaccine IN0-4800, which showed that the vaccine can produce a strong neutralizing antibody and T-cell immune response to SARS-CoV-2, is the third new coronavirus candidate vaccine in the world to begin clinical trials, and the first new coronavirus DNA vaccine to enter Phase I human clinical trials 4.2 mRNA vaccine mRNA vaccine is the in vitro synthesis of mRNA sequence containing specific antigens, which is delivered to the body by cell expression into antigen proteins, inducing the body to produce specific immune effects, and thus to achieve the role of immune protection MRNA vaccine, like DNA vaccine, can express intracellular antigens, but it solves the problem of low immunogenogenity of DNA vaccine and the generation of anti-carrier non-specific immunity, which has the advantage of short development and production time U.S pharmaceutical company Moderna, based on the development of pre-mRNA vaccines, and the National Institutes of Health jointly developed the world's first SARS-CoV-2 mRNA vaccine (mRNA-1273), and officially began human clinical trials on March 16, 2020 at Kaiser Medical Group's Washington Institute of Health in Washington; On The 4th, Moderna published the results of the first phase of clinical analysis of mRNA-1273, which showed that all volunteers produced high titer antibodies, which were more than those seen in most COVID-19 rehabilitation patients, and did not have serious adverse events Moderna announced on its website that it expects to begin Phase III clinical trials on July 27 on its new coronavirus vaccine mRNA-1273, which will assess the effectiveness, safety and immunogenicity of the vaccine for adults 18 years and older, with an estimated 30,000 subjects In a July 24 study published in the journal Cell, researchers from Qin Chengfeng of the Chinese Academy of Military Medicine and others developed a new mRNA new coronavaccinee, which in mouse and non-human primate models can stimulate immune responses and induce neutralizing antibodies; For vaccine products, which are expected to significantly reduce cold-chain requirements for transportation, the mRNA new crown vaccine was approved for clinical trials on June 19 Pfizer and BioNTech also recently announced further results of their new mRNA vaccine Phase 1 clinical trials on medRxiv, noting that the mRNA vaccine can induce both effective antibody response and T-cell response Photo Source: factly.in5, recombinant viral vector vaccine recombinant virus vector vaccine is a virus as a vector, the antigen gene recombined into the virus genome, using a recombinant virus that can express antigen genes Based on the successful development of ebola vaccine, the team of academicians from the Institute of Bioengineering of the Institute of Military Medical Sciences of the Academy of Military Sciences, in conjunction with Considine BioCO, quickly carried out research on pharmaceutical, pharmacological, pharmacological and pharmaceutical toxicology of the recombinant SARS-CoV-2 vaccine, and quickly completed the design, recombinant toxicity construction, and conducted a clinical trial review of vaccine safety, effectiveness, broad spectrum and quality in March 2020 The vaccine is a recombinant viral vector vaccine based on type 5 replication defective adenovirus as a vector expression of the SARS-CoV-2 S protein The focus of Phase I clinical studies trials is to determine human tolerance for different doses of vaccines by observing the safety of vaccine use On April 12, 2020, the vaccine entered Phase II clinical trials, the world's only SARS-CoV-2 vaccine to enter Phase II clinical trials in humans Compared with Phase I clinical trials, Phase II clinical trials liberalized the upper age limit, allowing some older volunteers over the age of 60 to join them, and The Phase II clinical study trial was designed to further analyze and confirm the results of the vaccine's initial effectiveness and safety in the population, and to determine the vaccine's immune procedures and immune dose Meanwhile, AzD-1222, a candidate vaccine for adenovirus vectors developed by AstraZeneca and Oxford University, announced in May that it had launched Phase II/III clinical trials, including 10,260 participants, and would be completed in August 2021 On July 20th, The Lancet magazine introduced clinical trials of two new crown vaccines in China and the United Kingdom, respectively, and the two "stars" on the adenovirus vector vaccine route showed a "double male rivalry" One was developed by the Chinese Academy of Engineering's Chen Wei academician team and Consino Bio, and the other was developed by Oxford University and AstraZeno From the experimental results, both vaccines can achieve an immune response to SARS-CoV-2 and induce an efficient Immune Response to T-cells In the clinical phase 2 trial of the non-replicated type 5 adenovirus (Ad5) new coronavirus vaccine presented by the Chinese team, 508 participants received high doses (1E11 virus particles, n-253), low doses (5E10 virus particles, n-129) vaccines, and placebo (n-126) injections Both the high-dose group and the low-dose group were able to induce a significant neutralizing antibody immune response to live SARS-CoV-2, and the participants neutralized the neutralized antibody's geometric average titer (GMT) of 19.5 and 18.3, respectively In the high-dose group, 148 people (59%) had a serum transformation of neutralizing antibodies to live SARS-CoV-2 responses, while 61 people (47%) had data in the low-dose group In the 1/2 clinical trial of the AZD1222avirus vector vaccine (ChAdOx1) conducted by British researchers, 1077 participants were vaccinated against ChAdOx1 nCoV-19 (n -543) and the meningococcal combination vaccine AMenCWY (n s 534) respectively The average age of the participants was 35 years (IQR 28-44 years), and more than 90% of the participants were Caucasian The results showed that the volunteers were vaccinated with ChAdOx1-nCoV-19 on the 7th day of the cellular immune response, and the 14th day of specific T response peaked (ELISPOT 856/10e6 PBMC), until the 56th day of the circulation remained at a high level !--/ewebeditor:!--webeditor: "" -- Of course, researchers also face a number of problems and challenges in the development of the new crown vaccine, such as weak subimmune progenition of the vaccine, incomplete virus inactivation, disease risk, and safe mass production COVID-19 is the most difficult and pass-through for humans to prevent and control in decades.