Augmented neutralization of SARS‐CoV‐2 Omicron variant by boost vaccination and monoclonal antibodies

Abstract

Effective vaccines and monoclonal antibodies have been developed against coronavirus disease 2019 (COVID‐19) caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2). However, the appearance of virus variants with higher transmissibility and pathogenicity is a major concern because of their potential to escape vaccines and clinically approved SARS‐CoV‐2‐ antibodies. Here, we use flow cytometry‐based binding and pseudotyped SARS‐CoV‐2 neutralization assays to determine the efficacy of boost immunization and therapeutic antibodies to neutralize the dominant Omicron variant. We provide compelling evidence that the third vaccination with BNT162b2 increases the amount of neutralizing serum antibodies against Delta and Omicron variants, albeit to a lower degree when compared to the parental Wuhan strain. Therefore, a third vaccination is warranted to increase titers of protective serum antibodies, especially in the case of the Omicron variant. We also found that most clinically approved and otherwise potent therapeutic antibodies against the Delta variant failed to recognize and neutralize the Omicron variant. In contrast, some antibodies under preclinical development potentially neutralized the Omicron variant. Our studies also support using a flow cytometry‐based antibody binding assay to rapidly monitor therapeutic candidates and serum titers against emerging SARS‐CoV‐2 variants.

SARS-CoV-2 spike opening dynamics and energetics reveal the individual roles of glycans and their collective impact

“…Of note, the epitopes of antibodies chosen here are in the NTD and RBD of the spike, the primary regions of variant mutations with effective neutralization evasion 5,62,63 . Impacted antibodies include STE90-C11, 4-8, S2M11, BD-368-2 by Omicron BA.1 62,64,65 and increased S309 escape by Omicron BA.2, BA.4/BA.5 63 . In the latter case, the loss of neutralization involves a region proximal to the N343 glycan, highlighting the important role of glycans in the immune response.…”

Rapid decline in vaccine-boosted neutralizing antibodies against SARS-CoV-2 Omicron variant

“…These Omicron sublineages share a subset of spike mutations but individually also contain unique spike mutations. 4 A single homologous vaccine boost after a primary series of either the BNT162b2 (Pfizer-BioNTech) or mRNA-1273 (Moderna) vaccines generates high titers of neutralizing antibodies to Omicron; [5][6][7] however, little is known about the durability of the response and the impact of heterologous vaccine boosting. As part of an ongoing study evaluating homologous and heterologous booster vaccines, 8 we assessed the magnitude and short-term durability of neutralizing activity against Omicron.…”

Susceptibility of SARS-CoV-2 Omicron Variants to Therapeutic Monoclonal Antibodies: Systematic Review and Meta-analysis

“…The exceptions included two studies in which the Omicron BA.1 sequence also contained A701V ( 9 , 14 ) and three studies in which the pseudotyped virus spike contained Q493K rather than Q493R ( 32 , 46 , 54 ). Several studies explicitly reported using pseudotyped viruses containing spike cytoplasmic tail truncations ( 16 , 23 , 32 , 36 , 42 , 54 ). This is a common practice used to increase the expression of spike proteins that may not have been consistently reported.…”