Nature sub-magazine review sourd depth! Treatment of PASSIVE antibody therapy for COVID-19!

, June 30, 2020 /

/BIOON/ -- In a recent review published in the International Journal ofNature Reviews Immunology, researchers from Harvard Medical School discussed the progress of research on the treatment of PASSIVE antibody therapy for COVID-19For more than a century, when pathogens appeared, scientists have been trying to extract plasma from the body of recovered patients as a treatment, and while people around the world are waiting for testing and safe development of the SARS-CoV-2 vaccine, the rapid separation and engineering modification of antiviral monoclonal antibodies has provided a very attractive option for passive immunity in populationspassive immunity using the plasma of the recovery period consists mainly of delivering the decellular blood from the body of the person recovering from infection to the body of the infected or at risk of infection; Some of the most convincing studies supporting the use of restorative plasma in acute viral infections came from studies of Argentine haemorrhagic fever, a disease caused by the Argentine haemorrhagic fever virus with a fatality rate of 15-30%, and in a prospective study involving more than 80 cases of Argentine haemorrhagic fever, the researchers said that after receiving pre-determined recovery plasma, the subjects developed a series of neutralizing antibody dropsThe recovery plasma that carries high levels of neutral antibody titer (adjusted dose sized according to the weight of each receptor) is necessary to achieve therapeutic results, with no deaths in the highest titer group (34 people), and a retrospective analysis reveals the importance of providing plasma within 8 days of onset, and now the recovery plasma can be used to treat Argentine haemorrhagic feverinfusion recovery plasma does ndegrees do not seem to help the recent Ebola outbreak, however, neutralizing the titration of patients after infusion recovery plasma was found to be low, and in a retrospective study, researchers analyzed SARS patients treated with steroids and antiviral ribavirin and found that those treated with recovery plasma treatment tended to be discharged earlier, while the neutralizing of the infusion plasma may not be standardizedPhoto Credit Abraham, JRev Nat Immunoldoi:10.1038/s41577-020-0365-7
in a recent prospective non-control study involving patients with severe COVID-19, researcher Duan et alinfusion of high lysine neutralization plasma from patients cured of COVID-19, and active plasma, after infusion, the body's blood The rapid increase in neutralizing antibody titer, the presence of SARS-CoV-2 virus in the patient's blood, and the patient's clinical symptoms improved; another study showed that after the first detection of the virus shedding, the recovery plasma treatment, which took more than 20 days on average, had a significant effect on the removal of the virus, but had no effect on the patient's mortality, suggesting that the blood transfusion may have taken longer than the patient's duration of treatmentcurrent pandemic may be an opportunity to help researchers conduct randomized controlled studies to support the use of restorative plasma in the treatment of COVID-19, whereas, ideally, such studies should include a group of subjects receiving pre-determined high-titer and active recovery plasma and a group of subjects receiving non-immune plasma as a controlBecause COVID-19 may involve at least two stages, first the virus replicates in tissue damage and then the virus is removed;recovery plasma often has several limitations, including differences between batches and blood type matching requirements, and samples must also be screened for blood-borne pathogens (hepatitis viruses, HIV, parasites, etc.); monoclonal antibody administration may be an alternative treatment for recovery-phase serum, and current techniques can quickly recover antiviral monoclonal antibodies or antibody derivatives, including selective methods of usingyeastand in vitro-based immunoasic serotonouresWith subsequent antibody humanization, antigen-specific single B-cell sorting, or EB virus B cell immortalization modification, the latter two methods include obtaining blood samples from the recovery patient body, while monoclonal antibodies can rapidly scale up tests during disease outbreaks, notably mAb14 (containing a single antibody) and REGN-EB3 (three antibody mixtures), in arandomized clinical trialBoth agents showed effects on Ebola virus infectionantibodies have two functional ends, the Fab arm can interact with antigens, the Fc domain interacts with adaptive and congenital immune system components, including NK cells, phagocytosis and complements; Neutralizing the antibody effect functions given to the active, targeted epitope and Fc region, and in order to achieve the desired effect and pharmacodynamic performance, antibody engineering modifications tend to switch between the same type and subtype, modify fc polysaccharides, or introduce amino acid substitutes to repair affinity between the Fc region and the Fc receptorSome antibodies may have adverse effects, such as antibody-dependent enhancement (ADE) of infected immune cells (mononucleoblasts, macrophages, and B cells), which are now described as being used in vitro and in vivo to develop antibodies to the cat coronavirus S protein, while ADE-promoted antibodies can also be removed during therapeutic candidate antibodies selection, while the Fc domain can be modified to avoid the ADE effecthave studies of antibodies that potentially neutralize SARS-CoV-2, including antibodies isolated from patients with COVID-19 recovery, which reduce the lung burden of animal-model viral RNA, which may be tested during a pandemicSo what key epitopes of the S protein can be targeted by neutralizing antibodies in the restored plasma? How many neutral antibody epitopes can simultaneously target the S protein that acts SARS-CoV-2? Which Fc receptors bind to antibodies to produce optimal antiviral activity, so as not to exacerbate an excessive immune response? Although coronaviruses have high-fidelity extrasothine gene products in genome replication, obtaining escape mutations from antibodies may still be a problemin principle, mutations affecting the neutralizing of antibodies may occur when the virus spreads during a pandemic, and a mixture of monoclonal antibodies (not a single formulation) may reduce the likelihood of neutralizing escape; Whether the candidate vaccine has different efficacy in different populations (e.gthe elderly) is yet to be determined, and passive antibody therapy in susceptible populations may be a bridge to vaccine development, which may be used for prevention in populations in special environments such as nursing homes, and for all preparations, appropriate controlsclinical trialsand an effective treatment time window may be key to the next study(BioValleyBioon.com)References:Abraham, JPassive antibody therapy in COVID-19
Nat Rev Immunol 20, 401-403 (2020) doi: 10.1038/s41577-020-0365-7
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