RT Journal Article
SR Electronic
T1 Engineered receptor binding domain immunogens elicit pan-coronavirus neutralizing antibodies
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.12.07.415216
DO 10.1101/2020.12.07.415216
A1 Blake M. Hauser
A1 Maya Sangesland
A1 Evan C. Lam
A1 Jared Feldman
A1 Ashraf S. Yousif
A1 Timothy M. Caradonna
A1 Alejandro B. Balazs
A1 Daniel Lingwood
A1 Aaron G. Schmidt
YR 2020
UL http://biorxiv.org/content/early/2020/12/08/2020.12.07.415216.abstract
AB Effective countermeasures are needed against emerging coronaviruses of pandemic potential, similar to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Designing immunogens that elicit broadly neutralizing antibodies to conserved viral epitopes on the major surface glycoprotein, spike, such as the receptor binding domain (RBD) is one potential approach. Here, we report the generation of homotrimeric RBD immunogens from different sarbecoviruses using a stabilized, immune-silent trimerization tag. We find that that a cocktail of homotrimeric sarbecovirus RBDs can elicit a neutralizing response to all components even in context of prior SARS-CoV-2 imprinting. Importantly, the cross-neutralizing antibody responses are focused towards conserved RBD epitopes outside of the ACE-2 receptor-binding motif. This may be an effective strategy for eliciting broadly neutralizing responses leading to a pan-sarbecovirus vaccine.Competing Interest StatementThe authors have declared no competing interest.