Broad strategies for neutralizing SARS-CoV-2 and other human coronaviruses with monoclonal antibodies

Abstract

Antibody therapeutics and vaccines for coronavirus disease 2019 (COVID-19) have been approved in many countries, with most being developed based on the original strain of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). SARS-CoV-2 has an exceptional ability to mutate under the pressure of host immunity, especially the immune-dominant spike protein of the virus, which is the target of both antibody drugs and vaccines. Given the continuous evolution of the virus and the identification of critical mutation sites, the World Health Organization (WHO) has named 5 variants of concern (VOCs): 4 are previously circulating VOCs, and 1 is currently circulating (Omicron). Due to multiple mutations in the spike protein, the recently emerged Omicron and descendent lineages have been shown to have the strongest ability to evade the neutralizing antibody (NAb) effects of current antibody drugs and vaccines. The development and characterization of broadly neutralizing antibodies (bNAbs) will provide broad strategies for the control of the sophisticated virus SARS-CoV-2. In this review, we describe how the virus evolves to escape NAbs and the potential neutralization mechanisms that associated with bNAbs. We also summarize progress in the development of bNAbs against SARS-CoV-2, human coronaviruses (CoVs) and other emerging pathogens and highlight their scientific and clinical significance.

A human antibody potently neutralizes RSV by targeting the conserved hydrophobic region of prefusion F

“…We screened a cohort of 30 blood samples and selected one donor with both a high serum antibody binding titre against RSV pre-F and a high in vitro neutralizing titre against RSV (Figure S1A in Supporting Information). We then conducted single-cell PCR experiments to generate hmAbs from memory B cells as previously described using dual-labelled RSV pre-F as the bait (Figure S1B in Supporting Information) (Ling et al, 2022). Total 23-specific antibodies were generated and then their binding activities to pre-F protein of A2 (subtype A) and B9320 (subtype B) were tested and characterized (Table 1).…”

Enhanced potency of an IgM-like nanobody targeting conserved epitope in SARS-CoV-2 spike N-terminal domain

“…However, the epitopes in the RBD are susceptible to immune escape and mutations, resulting in antibody resistance. 7 – 9 Although BA.2.86 does not demonstrate more resistance to human sera than XBB.1.5 and EG.5.1, 10 its descendant variant JN.1 continues to evolve and demonstrates a stronger immune evasion to monoclonal antibodies (mAbs) targeting RBD. 11 Furthermore, the previously-authorized mAbs targeting RBD have demonstrated reduced or lost efficacy against the Omicron and its sub-variants, causing their emergency use authorizations to be revoked ( https://www.fda.gov/ ).…”