Monoclonal antibodies (mAbs) are produced by a single B-lymphocyte clone and have high specificity for their target antigen. Since their introduction in 1985, mAbs have been used for various therapeutic and prophylactic purposes, such as the treatment of malignancies, autoimmune diseases, infectious organisms, and drug reversal purposes.
SARS-CoV-2 is the virus that causes COVID-19, and like other viruses in the betacoronavirus genus, several crucial stages of the SARS-CoV-2 life cycle can be potentially inhibited by mAbs. By binding to antigens found on the surface of SARS-CoV-2, mAbs can neutralize the viral proteins and prevent infection of human cells, reducing the severity and duration of illness.1
Monoclonal Antibodies in COVID-19 Treatment
Although several mAb therapies were developed and granted emergency use authorizations for COVID-19 treatment, the high frequency of the Omicron variant and emerging resistant subvariants caused them to be revoked by the FDA. These therapies included bamlanivimab, casirivimab, and imdevimab. Now, only Actemra (tocilizumab) may be used to treat severe COVID-19 illness for emergency use, effective since December 21, 2022.2 Actemra indirectly targets SARS-CoV-2 by blocking the interleukin-6 (IL-6) receptor. IL-6 is a pro-inflammatory cytokine and an anti-inflammatory myokine that regulates the immune response, inflammatory reaction and bone metabolism.3
MAbs have been shown to be efficient in reducing viral load and improving clinical outcomes, and they still have major benefits and potential as COVID-19 treatments. A study by Andreano et al. identified 453 neutralizing antibodies through single-cell sorting of 4,277 SARS-CoV-2 spike protein-specific memory B cells. Among these, the most potent antibodies recognized the spike protein receptor-binding domain, and subsequently the S1 domain, spike protein trimer, and S2 subunit. By targeting the viral spike protein, mAbs can prevent viral entry.4
Monoclonal Antibodies in COVID-19 Prevention
For pre-exposure prophylaxis, the FDA had previously authorized Evusheld (tixagevimab co-packaged with cilgavimab). However, on January 26, 2023, the FDA revoked its emergency use in the U.S. due to certain variants no longer being neutralized.2 Evusheld would bind to distinct sites on the SARS-CoV-2 spike protein and were optimized with half-life extension and reduced Fc receptor and complement C1q binding.5
The main challenge for mAbs as a COVID-19 therapeutic or prophylactic is the emerging variants and lowered efficacy. There is also a need for broader-based therapies, since Omicron infections may be less clinically severe than infections with earlier variants.
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References:
Brobst B, Borger J. Benefits and Risks of Administering Monoclonal Antibody Therapy for Coronavirus (COVID-19) [Updated 2023 May 7]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023
Nishimoto, N., Miyasaka, N., Yamamoto, K., Kawai, S., Takeuchi, T., & Azuma, J. (2009). Extended report: Long-term safety and efficacy of tocilizumab, an anti-IL-6 receptor monoclonal antibody, in monotherapy, in patients with rheumatoid arthritis (the STREAM study): Evidence of safety and efficacy in a 5-year extension study. Annals of the Rheumatic Diseases, 68(10), 1580-1584. https://doi.org/10.1136/ard.2008.092866
Andreano, E., Nicastri, E., Paciello, I., Pileri, P., Manganaro, N., Piccini, G., Manenti, A., Pantano, E., Kabanova, A., Troisi, M., Vacca, F., Cardamone, D., Santi, C. D., Torres, J. L., Ozorowski, G., Benincasa, L., Jang, H., Genova, C. D., Depau, L., . . . Rappuoli, R. (2021). Extremely potent human monoclonal antibodies from COVID-19 convalescent patients. Cell, 184(7), 1821-1835. https://doi.org/10.1016/j.cell.2021.02.035
