RT Journal Article SR Electronic T1 Driving potent neutralization of a SARS-CoV-2 Variant of Concern with a heterotypic boost JF bioRxiv FD Cold Spring Harbor Laboratory SP 2021.04.03.438330 DO 10.1101/2021.04.03.438330 A1 Sheward, Daniel J. A1 Mandolesi, Marco A1 Kim, Changil A1 Hanke, Leo A1 Vidakovics, Laura Perez A1 McInerney, Gerald A1 Hedestam, Gunilla B. Karlsson A1 Murrell, Ben YR 2021 UL http://biorxiv.org/content/early/2021/04/05/2021.04.03.438330.abstract AB The emergence of SARS-CoV-2 Variants of Concern (VOCs) with mutations in key neutralizing antibody epitopes threatens to undermine vaccines developed against the pandemic founder variant (Wu-Hu-1). Widespread vaccine rollout and continued transmission are creating a population that has antibody responses of varying potency to Wu-Hu-1. Against this background, it is critical to assess the outcomes of subsequent booster vaccination with variant antigens. It is not yet known whether such heterotypic vaccine boosts would be compromised by original antigenic sin, where pre-existing responses to a prior variant dampen responses to a new one, or whether the primed memory B cell repertoire would bridge the gap between Wu-Hu-1 and VOCs. Here, we show that a single adjuvanted dose of receptor binding domain (RBD) protein from VOC 501Y.V2 (B.1.351) drives an extremely potent neutralizing antibody response capable of cross-neutralizing both Wu-Hu-1 and 501Y.V2 in rhesus macaques previously immunized with Wu-Hu-1 spike protein.Competing Interest StatementThe authors have declared no competing interest.