PT  - JOURNAL ARTICLE
AU  - Daniel J. Sheward
AU  - Marco Mandolesi
AU  - Changil Kim
AU  - Leo Hanke
AU  - Laura Perez Vidakovics
AU  - Gerald McInerney
AU  - Gunilla B. Karlsson Hedestam
AU  - Ben Murrell
TI  - Driving potent neutralization of a SARS-CoV-2 Variant of Concern with a heterotypic boost
AID  - 10.1101/2021.04.03.438330
DP  - 2021 Jan 01
TA  - bioRxiv
PG  - 2021.04.03.438330
4099  - http://biorxiv.org/content/early/2021/04/05/2021.04.03.438330.short
4100  - http://biorxiv.org/content/early/2021/04/05/2021.04.03.438330.full
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.