Status and Developing Strategies for Neutralizing Monoclonal Antibody Therapy in the Omicron Era of COVID-19

Abstract

The monoclonal antibody (mAb)-based treatment is a highly valued therapy against COVID-19, especially for individuals who may not have strong immune responses to the vaccine. However, with the arrival of the Omicron variant and its evolving subvariants, along with the occurrence of remarkable resistance of these SARS-CoV-2 variants to the neutralizing antibodies, mAbs are facing tough challenges. Future strategies for developing mAbs with improved resistance to viral evasion will involve optimizing the targeting epitopes on SARS-CoV-2, enhancing the affinity and potency of mAbs, exploring the use of non-neutralizing antibodies that bind to conserved epitopes on the S protein, as well as optimizing immunization regimens. These approaches can improve the viability of mAb therapy in the fight against the evolving threat of the coronavirus.

Impact of COVID‐19 monoclonal antibodies on outcomes of COVID‐19 infection in hematopoietic stem cell transplant and chimeric antigen receptor therapy recipients

“…Current approaches underway include targeting new portions of the virus' receptor binding site (such as with the new broadly neutralizing MCA S728-1157), targeting evolutionarily conserved motifs that are not as readily mutated, and cocktails combining MCA with different targets (such as AZD5156, a combination of AZD3152 and AZD1061). 22,18,[40][41][42] Regardless of the mechanism, the development of MCA with activity against COVID-19 remains an important component in the provision of passive immunity against COVID-19 for HSCT and CAR-T recipients that are not as robustly served by active immunization, and who are at greater risk of severe complications without it.…”

From Detection to Protection: Antibodies and Their Crucial Role in Diagnosing and Combatting SARS-CoV-2

“…They hinder the interaction between the viral envelope and cell receptors, effectively preventing viral entry and replication, and safeguarding host cells from infection [139]. This mAb-based therapy is particularly valuable for individuals with weakened immune responses to vaccines, including people from the elderly and high-risk groups, and immunocompromised patients [140]. These antibodies, whether administered individually or as cocktails (combinations of two or more mAbs), have been widely endorsed by various authorities [141].…”

Current development of severe acute respiratory syndrome coronavirus 2 neutralizing antibodies (Review)

“…Large-scale preparations of specifically targeting mAbs that are of high purity with potent neutralizing activity can render them powerful tools for the prevention and treatment of infectious diseases ( 23 ). For SARS-CoV-2, specific B cells have been obtained from patients recovered from COVID-19 to produce large quantities of humanized mAbs through numerous methods, including mouse hybridoma fusion, single B cell sorting, phage display and transgenic mice and antibody screening technologies ( 24 – 26 ). A number of NAbs against SARS-CoV-2 have been developed.…”