Structural basis for accommodation of emerging B.1.351 and B.1.1.7 variants by two potent SARS-CoV-2 neutralizing antibodies

Cerutti, Gabriele; Rapp, Micah; Guo, Yicheng; Bahna, Fabiana; Bimela, Jude; Madan, Bharat; Yu, Jian; Wang, Pengfei; Liu, Lihong; Huang, Yaoxing; Ho, David D.; Kwong, Peter D.; Sheng, Zizhang; Shapiro, Lawrence

doi:10.1016/j.str.2021.05.014

Cited by 50 publications

(31 citation statements)

References 66 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Class IV antibodies, e.g. 1-57, 2-7, S309 and BD-812, hold the greatest potential for harboring ultra-potent neutralization activity and markedly high tolerance to most VOCs (63,67). Not surprisingly, all class IV antibodies, but CV07-270, exhibited excellent neutralizing breadth and potency to VOCs (Fig.…”

Section: Main Textmentioning

confidence: 94%

A third dose of inactivated vaccine augments the potency, breadth, and duration of anamnestic responses against SARS-CoV-2

Wang

Cao

Zhou

et al. 2021

Preprint

View full text Add to dashboard Cite

Emergence of variants of concern (VOC) with altered antigenic structures and waning humoral immunity to SARS-CoV-2 are harbingers of a long pandemic. Administration of a third dose of an inactivated virus vaccine can boost the immune response. Here, we have dissected the immunogenic profiles of antibodies from 3-dose vaccinees, 2-dose vaccinees and convalescents. Better neutralization breadth to VOCs, expeditious recall and long-lasting humoral response bolster 3-dose vaccinees in warding off COVID-19. Analysis of 171 complex structures of SARS-CoV-2 neutralizing antibodies identified structure-activity correlates, revealing ultrapotent, VOCs-refractory and broad-spectrum antigenic patches. Construction of immunogenic and mutational heat maps revealed a direct relationship between "hot" immunogenic sites and areas with high mutation frequencies. Ongoing antibody somatic mutation, memory B cell clonal turnover and antibody composition changes in B cell repertoire driven by prolonged and repeated antigen stimulation confer development of monoclonal antibodies with enhanced neutralizing potency and breadth. Our findings rationalize the use of 3-dose immunization regimens for inactivated vaccines.

show abstract

Section: Main Textmentioning

confidence: 94%

A third dose of inactivated vaccine augments the potency, breadth, and duration of anamnestic responses against SARS-CoV-2

Wang

Cao

Zhou

et al. 2021

Preprint

View full text Add to dashboard Cite

show abstract

“…Despite its proximity to the epitope, however, 484 do not interact significantly with Fab 1-57. Structural modeling of the E484K mutation showed that the K484 residue was geometrically compatible with Fab 1-57 binding at serine 29 with a hydrogen bond (57). Interaction of wild-type RBD by antibody Fab 2-7 is dominated by connection proximal to the RBD loops formed by residues 438-451 and 495-502.…”

Section: Class 1 Antibodiesmentioning

confidence: 99%

“…Another Class I mAbs of interest are monoclonal antibodies Fab 1-57 and Fab 2-7 which bind to the RBD epitope outside the hotspot of evolutionary pressure (57). Recognition of wild-type RBD by Fab 1-57 is dominated by the heavy chain, which buries 533.7 Å surface area, with a minor 223.3 Å contribution by the light chain.…”

Section: Class 1 Antibodiesmentioning

confidence: 99%

Broadly-Neutralizing Antibodies Against Emerging SARS-CoV-2 Variants

2021

View full text Add to dashboard Cite

The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants have become a major concern in the containment of current pandemic. The variants, including B.1.1.7 (Alpha), B.1.351 (Beta), P1 (Gamma) and B.1.617.2 (Delta) have shown reduced sensitivity to monoclonal antibodies, plasma and/or sera obtained from convalescent patients and vaccinated individuals. Development of potent therapeutic monoclonal antibodies (mAbs) with broad neutralizing breadth have become a priority for alleviating the devastating effects of this pandemic. Here, we review some of the most promising broadly neutralizing antibodies obtained from plasma of patients that recovered from early variants of SARS-CoV-2 that may be effective against emerging new variants of the virus. This review summarizes several mAbs, that have been discovered to cross-neutralize across Sarbecoviruses and SARS-CoV-2 escape mutants. Understanding the characteristics that confer this broad and cross-neutralization functions of these mAbs would inform on the development of therapeutic antibodies and guide the discovery of second-generation vaccines.

show abstract

“…Emerging viral variants that exhibit increased infectivity and virulence emphasize the need for continued improvement in immunization and therapeutic approaches. Specifically, the B.1.1.7 (UK), B.1.351 (South Africa), P.1 (Brazil), and other strains demand careful attention ( 9 , 10 , 11 , 12 , 13 , 14 ). Exploring the detailed structures of anti-viral antibodies can provide critical understanding of means to attenuate viral adsorption and entry, and to prevent or retard ongoing infection and communal spread.…”

Section: Introductionmentioning

confidence: 99%

Structures of synthetic nanobody–SARS-CoV-2 receptor-binding domain complexes reveal distinct sites of interaction

Ahmad

Jiang

Boyd

et al. 2021

Journal of Biological Chemistry

View full text Add to dashboard Cite

Combating the worldwide spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the emergence of new variants demands understanding of the structural basis of the interaction of antibodies with the SARS-CoV-2 receptor-binding domain (RBD). Here we report five X-ray crystal structures of sybodies (synthetic nanobodies) including those of binary and ternary complexes of Sb16–RBD, Sb45–RBD, Sb14–RBD–Sb68, and Sb45–RBD–Sb68, as well as unliganded Sb16. These structures reveal that Sb14, Sb16, and Sb45 bind the RBD at the angiotensin converting enzyme 2 (ACE2) interface, and that the Sb16 interaction is accompanied by a large conformational adjustment of complementarity determining region 2 (CDR2). In contrast, Sb68 interacts at the periphery of the SARS-CoV-2 RBC/ACE2 interface. We also determined cryo-EM structures of Sb45 bound to the SARS-CoV-2 spike (S) protein. Superposition of the X-ray structures of sybodies onto the trimeric S protein cryo-EM map indicates that some sybodies may bind in both "up" and "down" configurations, but others may not. Differences in sybody recognition of several recently identified RBD variants are explained by these structures.

show abstract

Structural basis for accommodation of emerging B.1.351 and B.1.1.7 variants by two potent SARS-CoV-2 neutralizing antibodies

Cited by 50 publications

References 66 publications

A third dose of inactivated vaccine augments the potency, breadth, and duration of anamnestic responses against SARS-CoV-2

A third dose of inactivated vaccine augments the potency, breadth, and duration of anamnestic responses against SARS-CoV-2

Broadly-Neutralizing Antibodies Against Emerging SARS-CoV-2 Variants

Structures of synthetic nanobody–SARS-CoV-2 receptor-binding domain complexes reveal distinct sites of interaction

Contact Info

Product

Resources

About