Warning: This is a preliminary report that has not been peer-reviewed. It should not be regarded as conclusive, guide clinical practice/health-related behavior, or be reported in news media as established information.

Song G, Yuan M, Liu H, Capozzola T, Lin RN, Torres JL, He W-t, Musharrafieh R, Dueker K, Zhou P, Callaghan S, Mishra N, Yong P, Anzanello F, Avillion G, Vo AL, Li X, Makhdoomi M, Feng Z, Zhu X, Peng L, Nemazee D, Safonova Y, Briney B, Ward AB, Burton DR, Wilson IA, Andrabi R

Developing broad coronavirus vaccines requires identifying and understanding the molecular basis of broadly neutralizing antibody (bnAb) spike sites. In our previous work, we identified sarbecovirus spike RBD group 1 and 2 bnAbs. We have now shown that many of these bnAbs can still neutralize highly mutated SARS-CoV-2 variants, including the ...

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XBB.1.5. Structural studies revealed that group 1 bnAbs use recurrent germline encoded CDRH3 features to interact with a conserved RBD region that overlaps with class 4 bnAb site. Group 2 bnAbs recognize a less well-characterized site V on the RBD and destabilize spike trimer. The site V has remained largely unchanged in SARS-CoV- 2 variants and is highly conserved across diverse sarbecoviruses, making it a promising target for broad coronavirus vaccine development. Our findings suggest that targeted vaccine strategies may be needed to induce effective B cell responses to escape resistant subdominant spike RBD bnAb sites.

Date: Apr. 27, 2023

Status: Preliminary Report

View Source: doi: 10.1101/2023.04.26.538488

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