Broadly-Neutralizing Antibodies Against Emerging SARS-CoV-2 Variants

Abstract

The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants have become a major concern in the containment of current pandemic. The variants, including B.1.1.7 (Alpha), B.1.351 (Beta), P1 (Gamma) and B.1.617.2 (Delta) have shown reduced sensitivity to monoclonal antibodies, plasma and/or sera obtained from convalescent patients and vaccinated individuals. Development of potent therapeutic monoclonal antibodies (mAbs) with broad neutralizing breadth have become a priority for alleviating the devastating effects of this pandemic. Here, we review some of the most promising broadly neutralizing antibodies obtained from plasma of patients that recovered from early variants of SARS-CoV-2 that may be effective against emerging new variants of the virus. This review summarizes several mAbs, that have been discovered to cross-neutralize across Sarbecoviruses and SARS-CoV-2 escape mutants. Understanding the characteristics that confer this broad and cross-neutralization functions of these mAbs would inform on the development of therapeutic antibodies and guide the discovery of second-generation vaccines.

Limited Impact of Delta Variant’s Mutations on the Effectiveness of Neutralization Conferred by Natural Infection or COVID-19 Vaccines in a Latino Population

“…Another study found that a naturally infected individual produced uncommon genetic and structural characteristics and showed potent neutralization against authentic SARS-CoV-2 viruses, including VOCs [32]. These results are consistent with other reports [33][34][35] and highlight the need for more epidemiological data about the contribution of previously exposed individuals with naturally-acquired immunity to herd immunity. Overall, these issues are scarcely considered in any statistical model.…”

Deep Mutational Engineering of broadly-neutralizing and picomolar affinity nanobodies to accommodate SARS-CoV-1 & 2 antigenic polymorphism

“…Importantly, the gains in affinity observed for the engineered molecules translate into an increase in their potential to not only neutralize the interaction between RBD and the human ACE2, but also the entry of the SARS-CoV-2 virus into human cells. Unlike many class IV antibodies which often are weakly neutralizing, 40 our molecules demonstrate a strong capacity to neutralize the SARS-CoV-2 virus, with low EC50 in the ng/mL and picomolar range. Recently, rimteravimab, which is derived from VHH72 and incorporates a single substitution corresponding to S56A, has shown protection in mice and Syrian hamster animal models.…”

Deep mutational engineering of broadly-neutralizing nanobodies accommodating SARS-CoV-1 and 2 antigenic drift

“…Importantly, the gains in affinity here observed for the engineered molecules translate into an increase in their potential to not only neutralize the interaction between RBD and the human ACE2 but also the entry of the SARS-CoV-2 virus into human cells. Unlike many class IV antibodies, which often are weakly neutralizing, 42 our molecules demonstrate a strong capacity to neutralize the SARS-CoV-2 virus, with low EC50 in the ng/mL and picomolar range. Recently, rimteravimab (XVR011), a bivalent nanobody-Fc molecule derived from VHH72 that incorporates a single substitution corresponding to S56A, has shown protection in mice and Syrian hamster animal models.…”