Quick Look at the Anti-epidemic Monoclonal Antibodies that Target the Novel Coronavirus S Protein

The General Office of the National Health Commission and the Office of the National Administration of Traditional Chinese Medicine of China issued the COVID-19 Diagnosis and Treatment Scheme (Trial Version 6) on Feb. 19. It's worth noting that the scheme has proposed that "convalescent plasma can be used to treat" severe and critical patients from version 4.

Limited convalescent plasma

Convalescent plasma is provided by recovered novel coronavirus-infected patients. What resists to the virus infection is the antibody immunoglobulin contained in the plasma. Besides the broad-spectrum antiviral immunoglobulin contained in the plasma of ordinary people, convalescent plasma also has the specific immunoglobulin against the novel coronavirus. This antibody is therapeutic and preventive to treat infected persons and protect uninfected persons.

The President of Wuhan Jinyintan Hospital has launched an initiative to seek the donation of convalescent plasma. The plasma therapy has the most direct action and its efficacy is worth looking forward to from the perspective of the mechanism of action, however, the number of recovered patients is relatively small compared to the huge number of infected persons, and the scarce of the source of such raw material constitutes a natural limit to the large-scale promotion and use of such therapy.

Another possibility provided by monoclonal antibodies

Antibodies are secreted by plasma cells converted from B lymphocytes in vivo. Each B lymphocyte cell line can only produce one unique monoclonal antibody for a specific antigenic determinant. Through the antibody gene engineering technique, corresponding memory B cells are cloned and specific monoclonal antibodies against viruses are produced. The monoclonal antibodies so produced are derived from single B cell cloning and highly homogeneous and only for specific epitopes. There have been many monoclonal antibody drugs used in disease treatment.

In the development process of this technique, the sources of monoclonal antibody drugs have experienced the murine, chimeric, humanized, and fully human stages. Murine monoclonal antibodies are secreted by mouse hybridomas, however, their strong immunogenicity brings adverse reactions, while, the humanized and chimeric antibodies prepared through in-vitro antibody engineering methods have small adverse reactions, long half-lives, and good efficacy.

Theoretically, this technique also applies to the preparation of the specific immunoglobulin against the novel coronavirus. Compared to obtaining the antibody with the convalescent plasma, a significant advantage of this technique is that the related products are not restricted by the source of raw material and can be easily mass-produced to meet the treatment demand of a large number of patients.

SARS-CoV-2 spike protein

SARS-CoV-2 is one of the coronaviruses. The coronavirus was first separated from chicken in 1937 as a single-stranded, positive-strand RNA virus with a diameter of about 80-120nm. The viral pathogen SARS-CoV of SARS and the viral pathogen MERS-CoV of MERS also belong to the coronavirus family.

The spike protein (S protein) on the coronavirus’ outer shell can enter cells via angiotensin-converting enzyme 2 (ACE2) and transmembrane protease serine 2 (TMPRSS2). The NIH has discovered that ACE2 is the receptor of SARS-CoV-2. The recognized pathogenic process of SARS-CoV-2 is that the spike protein binds to human mucous epithelium ACE2 to make the virus enter human cells to induce the subsequent replication, assembly, spread, tissue damage, and immune system activation, etc.

Monoclonal antibodies that target the spike protein

Currently, the drug development strategies based on the mechanism of coronavirus infection are mainly in two directions: one is to stop the virus replication, and the other one is to stop viral entry and membrane fusion.

Given the role played by the spike protein in the pathogenic process of SARS-CoV-2, screening out the potentially effective monoclonal antibodies by targeting the spike protein is a direction in the global fight against SARS-CoV-2 epidemic.

Companies that are the fastest in developing such monoclonal antibodies are Vir Biotechnology and AbCellera. The monoclonal antibodies of those two companies are humanized. Besides this method, Regeneron and Flanders Institute for Biotechnology have provided the animal-sourced monoclonal antibody preparation scheme.

Vir Biotechnology has separated the spike protein monoclonal antibody from recovered patients using the individual B cell technology platform: Humabs BioMed and screened out 2 efficient SARS-CoV-2 monoclonal antibodies from the pseudo-protein system; AbCellera has separated the spike protein monoclonal antibody from recovered patients using the individual B cell platform (PPP); Regeneron has separated the spike protein monoclonal antibody using its VelocImmune mouse platform; Flanders Institute for Biotechnology has obtained the monoclonal antibody by the immunization of llamas.

Source: Biocentury

Furthermore, WuXi AppTec has reached an intention with the North American biotechnology company ImmunoPrecise to jointly develop the monoclonal antibodies against SARS-CoV-2.

It’s worth mentioning that according to a prospective, randomized, controlled study published on The New England Journal of Medicine in 2019, the monoclonal antibody mAb114 and the REGN-EB3 therapy could significantly reduce the case fatality rate of Ebola patients, with good therapeutic value for virus infection. In the battle against the Ebola virus, Vir Biotechnology discovered the monoclonal antibody mAb114, and Regeneron provided the REGN-EB3 (a cocktail of three monoclonal antibodies) therapeutic regimen. Those two regimens were both precedents of successful development and could endorse the companies’ monoclonal antibody techniques.

About  the Author:    

Xiaoyaowan, a pharmaceutical industry practitioner, a word carrier in the We-media era focusing on changes of the pharma industry.

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