RESUMEN
Monoclonal antibodies (mAbs) are the most promising and most intensively replenished type of bioactive pharmaceuticals. Currently, there are over 100 different mAbs approved by the FDA and other regulating agencies for treatment of oncological, infectious, systemic, autoimmune and other diseases. Design of antibodies neutralizing pathogens of socially significant infections, such as HIV, hepatitis viruses, SARS-CoV-2, is a separate direction. The SARS-CoV-2 pandemic has shown how urgent it is to have a technological platform enabling production of fully human antibodies. The development of recombinant DNA technology and antibody phage display enabled compilation of libraries of antigen-binding fragments and screening with target antigens. This review discusses the advantages and disadvantages of phage display, including use of single-domain antibody technology based on the heavy chain variable domain. We describe the state-of-the-art (and practical results of its application) technology enabling production of human antibodies by sorting and sequencing the genome of individual memory B cells, using monoclonal virus-neutralizing antibodies against SARS-CoV-2 as an example. The prospects of further development of the recombinant human antibody production technology are discussed;in particular, we consider creation of sequences of variable fragments of antibodies with the help of artificial intelligence. © 2022 Group of Companies Med Expert, LLC. All rights reserved.
RESUMEN
The parameters of the humoral response are an important immunological characteristic of donors who recovered from COVID-19 and vaccinated individuals. Analysis of the level of virus-binding antibodies has become widespread. The most accurate predictor of effective immune protection against symptomatic SARS-CoV-2 infection is the activity of virus-neutralizing antibodies. We determined virus-neutralizing activities in plasma samples of individuals (n = 111) who had COVID-19 from April to September 2020. Three independent methods were used: conventional with live virus, with virus-like particles pseudotyped with spike protein, and a surrogate virus-neutralization test (cVNT, pVNT and sVNT, respectively). For comparison, the levels of IgG, IgA and IgM antibodies against the receptor-binding domain of the SARS-CoV-2 spike protein were also evaluated. The levels of virus-binding as well as virus-neutralizing antibodies in cVNT and pVNT showed high heterogeneity. A comparison of cVNT and pVNT results showed a high correlation, sVNT results also correlated well with both cVNt and pVNT. To the greatest extent, the level of IgG antibodies correlated with the results of cVNT, pVNT and sVNT. These results can be used in the selection of plasmas that are best suited for transfusion and treatment of acute COVID-19. In addition, data on the virus-neutralizing activity of plasma are important for the selection of potential donors, for the isolation of SARS-CoV-2-specific B-lymphocytes, in order to further generate monoclonal virus-neutralizing antibodies.
RESUMEN
The review systematizes data on the role of infectious diseases and systemic inflammation in the pathogenesis of stroke. Various risk factors for stroke associated with pro-inflammatory reactions and their contribution to the pathogenesis of cerebrovascular pathology are analyzed. The interaction of systemic inflammation with hemostasis disturbances and clots formation, activation of autoreactive clones of cytotoxic lymphocytes, the progression of endothelial damage, and other processes is shown. Along with infection, these factors increase the risk of stroke. The key mechanisms of the pathogenesis from the development of acute or chronic inflammation to the preconditions of stroke are presented. The mechanisms of the acting of the infectious process as a trigger factor and/or medium-term or long-term risk factors of stroke are described. A separate section is devoted to the mechanisms of developing cerebrovascular diseases after COVID-19. Identifying an increased risk of stroke due to infection can be of great preventive value. Understanding of this risk by specialists followed by correction of drug therapy and rehabilitation measures can reduce the incidence of cerebrovascular complications in infectious patients.