Science Outlook: How to rapidly develop coVID-19 vaccines? What should I pay attention to?

May 27, 2020 /
BiovalleyBIOON /-- Rapid development of vaccines to prevent COVID-19 is a global imperative, and identifying stakes and potential barriers is critical because regulatory and medical decisions are based on interests: risk calculationThe ability to transmit pandemic viruses can be reduced by building mass immunity, and a key question is whether the spread of SARS-CoV-2 can be prevented by developing effective vaccines or by developing effective vaccines or by repeated infections reaching 60 to 70 percent in the next few yearsSince humans are still exposed to SARS-CoV-2 for the first time, the consequences of a repeat epidemic will be an unacceptably high mortality rate, severe economic damage and major changes to our way of lifeThe benefits of developing an effective vaccine are therefore significant, and even greater if deployed in a timely manner to prevent a repeat or continued epidemicvaccine development is usually in decades, it would be unprecedented to get approved vaccines that can be distributed on a large scale by the end of 2020 and even 2021However, new manufacturing platforms, structural antigen design, computational biology, protein engineering, and gene integration are now tools for rapid and precise vaccine manufacturingAntiviral vaccines can be divided into two main categoriesGene-based vaccines transmit gene sequences that encode protein antigens produced by host cellsThese vaccines include live viral vaccines, recombinant vaccines
vectors
or nucleic acid vaccinesProtein-based vaccines include fully inactivated viruses, individual viral proteins or subdomains, or viral proteins assembled in the form of particles, all of which are manufactured out of the bodyRecombinant vaccinesvector
and nucleic acid vaccines are best suited for rapid production because they are easier to adapt to platform production technologies, where upstream supply chains and downstream processes are the same for every product Precise antigen delivery can be achieved by understanding the atomic structure of vaccine antigens and the target antigen epitope preserved in vaccines is critical to providing the correct protein for the configuration of antibody-mediated immune CoV protrusion proteins are displayed on the surface of the virus and help the virus invade It completes this process through a large-scale reorganization that pulls the virus and the cell membrane together and fuses them Therefore, the protrusion protein is a dynamic substeady state protein, there are two main structural states: pre-fusion and post-fusion conformation Demonstrating the surface contours and chemical properties of this antigen, which retains the original primary fusion pre-protrusion protein, will retain the antigen epitope required for high-quality neutralizing antibody reactions The formulation and delivery of vaccines can also affect the function and reaction patterns of T cells The gene-based vaccine induces CD8-T cells and produces cd4-T-assisted type 1 cell immune response, which has good antiviral characteristics The adjuas can not only be used to improve the strength and durability of antibody reactions caused by protein vaccines, but also affect cytokine patterns of T-cell sources to regulate immune responses safety is the primary goal of vaccination for healthy people, which may exacerbate subsequent SARS-CoV-2 infections This has happened before There were two different syndromes associated with vaccine-boosted diseases One is an enhanced response to antibody dependence (ADE), the other is a vaccine-enhanced respiratory disease (VAERD), an Fc (the tail end of the antibody) mediated by an enhanced response, usually associated with insect-borne viral infections, such as dengue virus (3) ADE's mechanism designs viral antibody complexes to increase the binding capacity of cells that express FcR, which promotes the virus to enter the cells This is more likely to occur when vaccine-induced antibodies are not effectively neutralizing the virus due to lack of concentration or affinity or specificity errors image source: Science study also found that ADE is linked to cat-infectious peritonitis virus (FIPV), a coronavirus that targets macrophages and causes systemic vasculitis-like diseases In cats previously inoculated with an inactivated virus containing aluminum adhesis, antibody-mediated disease enhancement was found after infection Although THE TENDENCY OF SARS-COV-2 CELLS HAS NOT BEEN FULLY DETERMINED, IT IS A RESPIRATORY VIRUS THAT IS VERY DIFFERENT FROM FIPV CAUSED BY RESPIRATORY EPITHELIAL CELL INFECTIONS CONSISTENT WITH CORONAVIRUSES THAT CAUSE MERS-COV AND SARS-COV-1 Based on the detection of viral gene fragments by polymerase chain reaction (PCR), the researchers found that SARS-CoV-1 occurred in the human B-cell lymphoma cell line cultured in vitro However, there is no experimental data in the body that suggests that the introduction of this antibody is related to the pathophysiology of respiratory coronaviruses such as SARS-CoV-1, and that no infectious virus is produced even in vitro, suggesting that the replication cycle has failed VAERD is a unique clinical syndrome found in experiments in the 1960s using a fully inactivated viral vaccine against measles and respiratory syncytial virus (RSV) in infants Insufficient doses of antigens for injection, in particular the use of antigens with incorrect conformation, can lead to two main immunological phenomena associated with enhanced respiratory diseases (ERD) One is a relatively high ratio of binding and neutralizing antibodies, and if a large number of antigens can be combined but not neutralized by the virus, high titration viruses may lead to immunocompound deposition and complement activation Another phenomenon is that RSV infection after infighting of the completein virus can lead to allergic inflammation This process produces a large number of cytokines interleukin-4 (IL-4), IL-5 and IL-13, which lead to increased mucus production, eosinophil cell collection, airway hyperreactivity, and weakened cell-dissolved T-cell activity, collectively known as type 2 auxiliary T-cell immune response (TH2) These conditions can increase airway dysfunction and delay virus removal Therefore, avoiding the TH2 immune response may be important, especially in young children with small airways that are prone to obstruction similar T-cell and cytokine response patterns have been observed in mice, rats, cattle and non-human primate models that are jointly injected with alum and total inactivated viruses Almost all vaERD-inactivated viruses are used Animal experiments need to note that allergic inflammation can also be triggered by the use of the same cell line and media to culture vaccine viruses and challenging viruses Even without viral antigens, cell composition and media additives can cause the sensitivity of these proteins
in the development of the COVID-19 vaccine, the previous work on RSV vaccineshould be taken into account to understand ways to reduce the risk of vaccine-enhanced disease syndrome By measuring the inducing effects of neutralizing antibodies, as well as demonstrating the potential for virus replication and disease protection in animal models, it will be important to demonstrate the potential for vaccine effectiveness in early clinical studies Equally important will be the use of the correct antigen of the conformation to induce high-quality, functionally related antibodies and to avoid inducing non-neutralizing antibodies and TH2 bias immune responses The use of limited diluted vaccines and examination of lung pathology characteristics of breakthrough infected animals after re-exposure should also help to assess people with possible abnormal pathology vaccinations the parameters of immunology parameters that define VAERD in the RSV animal model delayed broad industry involvement in vaccine development by about 30 years During a pandemic, it is reasonable to require that the candidate vaccine have certain qualities based on the initial immunogenicity of animals and conduct phase I clinical trials based on the evidence of human immunogens and animal model protection In the effectiveness trial (i.e phases 2 and 3 trials), the justification for extending the vaccine to thousands of subjects may require additional evidence that it is safe to vaccinate animals with limited doses of vaccine and in animals with breakthrough infections following the SARS-CoV-2 challenge Vaccine studies in animal models, accompanied by a wise assessment of candidate vaccines for healthy adults, and accelerated process development to expand production capacity, providead a path forward with the lowest risk for human subjects and provided significant potential benefits by accelerating the availability of COVID-19 vaccines (biovalleybioon.com) Reference: Rapid COVID-19 vaccine development