SARS-CoV-2 Beta variant infection elicits potent lineage-specific and cross-reactive antibodies

TLDR

The SARS‑CoV‑2 Beta variant resists neutralization by major antibody classes from patients and vaccinated individuals. The study isolated Beta‑specific and cross‑reactive RBD antibodies from infected patients. Serum from Beta‑infected patients displayed reduced cross‑neutralization of wild‑type virus, and the isolated Beta‑specific and cross‑reactive RBD antibodies revealed recruitment of VOC‑specific clonotypes and accommodation of Beta and Omicron mutations, sharing a public VH1‑58 clonotype that targets the RBD ridge, thereby advancing understanding of antibody responses shaped by antigenic drift and informing next‑generation vaccine and therapeutic design.

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Beta variant of concern (VOC) resists neutralization by major classes of antibodies from COVID-19 patients and vaccinated individuals. In this study, serum of Beta-infected patients revealed reduced cross-neutralization of wild-type virus. From these patients, we isolated Beta-specific and cross-reactive receptor-binding domain (RBD) antibodies. The Beta-specificity results from recruitment of VOC-specific clonotypes and accommodation of mutations present in Beta and Omicron into a major antibody class that is normally sensitive to these mutations. The Beta-elicited cross-reactive antibodies share genetic and structural features with wild type-elicited antibodies, including a public VH1-58 clonotype that targets the RBD ridge. These findings advance our understanding of the antibody response to SARS-CoV-2 shaped by antigenic drift, with implications for design of next-generation vaccines and therapeutics.