RT Journal Article
SR Electronic
T1 Increased Resistance of SARS-CoV-2 Variants B.1.351 and B.1.1.7 to Antibody Neutralization
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2021.01.25.428137
DO 10.1101/2021.01.25.428137
A1 Pengfei Wang
A1 Lihong Liu
A1 Sho Iketani
A1 Yang Luo
A1 Yicheng Guo
A1 Maple Wang
A1 Jian Yu
A1 Baoshan Zhang
A1 Peter D. Kwong
A1 Barney S. Graham
A1 John R. Mascola
A1 Jennifer Y. Chang
A1 Michael T. Yin
A1 Magdalena Sobieszczyk
A1 Christos A. Kyratsous
A1 Lawrence Shapiro
A1 Zizhang Sheng
A1 Manoj S. Nair
A1 Yaoxing Huang
A1 David D. Ho
YR 2021
UL http://biorxiv.org/content/early/2021/01/26/2021.01.25.428137.abstract
AB The Covid-19 pandemic has ravaged the globe, and its causative agent, SARS-CoV-2, continues to rage. Prospects of ending this pandemic rest on the development of effective interventions. Two monoclonal antibody (mAb) therapeutics have received emergency use authorization1,2, and more are in the pipeline3–6. Furthermore, multiple vaccine constructs have shown promise7, including two with ~95% protective efficacy against Covid-198,9. However, these interventions were directed toward the initial SARS-CoV-2 that emerged in 2019. Considerable viral evolution has occurred since, including variants with a D614G mutation10 that have become dominant. Viruses with this mutation alone do not appear to be antigenically distinct, however11. Recent emergence of new SARS-CoV-2 variants B.1.1.7 in the UK12 and B.1.351 in South Africa13 is of concern because of their purported ease of transmission and extensive mutations in the spike protein. We now report that B.1.1.7 is refractory to neutralization by most mAbs to the N-terminal domain (NTD) of spike and relatively resistant to a number of mAbs to the receptor-binding domain (RBD). It is modestly more resistant to convalescent plasma (~3 fold) and vaccinee sera (~2 fold). Findings on B.1.351 are more worrisome in that this variant is not only refractory to neutralization by most NTD mAbs but also by multiple potent mAbs to the receptor-binding motif on RBD, largely due to an E484K mutation. Moreover, B.1.351 is markedly more resistant to neutralization by convalescent plasma (~11-33 fold) and vaccinee sera (~6.5-8.6 fold). B.1.351 and emergent variants14,15 with similar spike mutations present new challenges for mAb therapy and threaten the protective efficacy of current vaccines.Competing Interest StatementThe authors have declared no competing interest.