Potent SARS-CoV-2 neutralizing antibodies directed against spike N-terminal domain target a single supersite

Cerutti, Gabriele; Guo, Yicheng; Zhou, Tongqing; Gorman, Jason; Lee, Myungjin; Rapp, Micah; Madan, Bharat; Yu, Jian; Bahna, Fabiana; Bimela, Jude; Huang, Yaoxing; Katsamba, Phinikoula S.; Liu, Lihong; Nair, Manoj S.; Rawi, Reda; Olia, Adam S.; Wang, Pengfei; Zhang, Baoshan; Chuang, Gwo Yu; Ho, David D.; Sheng, Zizhang; Kwong, Peter D.; Shapiro, Lawrence

doi:10.1016/j.chom.2021.03.005

Cited by 512 publications

(645 citation statements)

References 94 publications

Supporting

Mentioning

618

Contrasting

Unclassified

Order By: Relevance

“…Numerous neutralizing anti-RBD monoclonal antibodies (mAbs) have been characterized, the most potent of which block the RBD-ACE2 interaction (16, 17, [22][23][24][32][33][34][35][36][37]. Neutralizing against other region of the viral spike have also been identified (24,33,(38)(39)(40)(41)(42).…”

mentioning

confidence: 99%

mRNA vaccination boosts cross-variant neutralizing antibodies elicited by SARS-CoV-2 infection

Stamatatos

Czartoski

Wan

et al. 2021

Science

548

121

492

View full text Add to dashboard Cite

Emerging SARS-CoV-2 variants have raised concerns about resistance to neutralizing antibodies elicited by previous infection or vaccination. We examined whether sera from recovered and naïve donors collected prior to, and following immunizations with existing mRNA vaccines, could neutralize the Wuhan-Hu-1 and B.1.351 variants. Pre-vaccination sera from recovered donors neutralized Wuhan-Hu-1 and sporadically neutralized B.1.351, but a single immunization boosted neutralizing titers against all variants and SARS-CoV-1 by up to 1000-fold. Neutralization was due to antibodies targeting the receptor binding domain and was not boosted by a second immunization. Immunization of naïve donors also elicited cross-neutralizing responses, but at lower titers. Our study highlights the importance of vaccinating both uninfected and previously infected persons to elicit cross-variant neutralizing antibodies.

show abstract

mentioning

confidence: 99%

mRNA vaccination boosts cross-variant neutralizing antibodies elicited by SARS-CoV-2 infection

Stamatatos

Czartoski

Wan

et al. 2021

Science

548

121

492

View full text Add to dashboard Cite

show abstract

“…To date, advanced genomic approaches have identified thousands of variants of SARS-CoV-2 with multiple RBD mutations circulating due to natural selection 16,17 . The variability of RBD epitopes is of specific concern as such mutations might reduce vaccine efficacy, increase viral transmission, or impair acquired immunity by neutralizing antibodies 10,18,19 . For the pandemic to be brought under control, herd immunity must be achieved through vaccination.…”

mentioning

confidence: 99%

Immune response to SARS-CoV-2 variants of concern in vaccinated individuals

et al. 2021

View full text Add to dashboard Cite

SARS-CoV-2 is evolving with mutations in the receptor binding domain (RBD) being of particular concern. It is important to know how much cross-protection is offered between strains following vaccination or infection. Here, we obtain serum and saliva samples from groups of vaccinated (Pfizer BNT-162b2), infected and uninfected individuals and characterize the antibody response to RBD mutant strains. Vaccinated individuals have a robust humoral response after the second dose and have high IgG antibody titers in the saliva. Antibody responses however show considerable differences in binding to RBD mutants of emerging variants of concern and substantial reduction in RBD binding and neutralization is observed against a patient-isolated South African variant. Taken together our data reinforce the importance of the second dose of Pfizer BNT-162b2 to acquire high levels of neutralizing antibodies and high antibody titers in saliva suggest that vaccinated individuals may have reduced transmission potential. Substantially reduced neutralization for the South African variant further highlights the importance of surveillance strategies to detect new variants and targeting these in future vaccines.

show abstract

“…These antibodies, identified in separate studies of infected donors from around the world ( Barnes et al., 2020 ; Hansen et al., 2020 ; Lv et al., 2020 ; Pinto et al., 2020 ) were generally chosen for study due to their neutralization potency. Overall, these studies identified antibodies mainly targeting RBD ( Brouwer et al., 2020 ; Shi et al., 2020 ; Tortorici et al., 2020 ; Wu et al., 2020 ), with some NTD-directed neutralizers ( Cerutti et al., 2021 ; Chi et al., 2020 ), with antibodies of the same class often identified in multiple studies. The residue-level antibody-interaction frequencies we present for RBD are likely to represent a reasonable estimate of relative frequencies, but only for the most potent and most frequent classes.…”

Section: Discussionmentioning

confidence: 99%

“…SARS CoV-2 S2P spike density was modeled using PDB entry 7L2E ( Cerutti et al., 2021 ), as initial template. The initial model for 1-57 Fab variable region was obtained using the SAbPred server ( Dunbar et al., 2016 ).…”

Section: Methodsmentioning

confidence: 99%

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

et al. 2021

Self Cite

View full text Add to dashboard Cite

Emerging SARS-CoV-2 strains, B.1.1.7 and B.1.351, from the UK and South Africa, respectively, show decreased neutralization by monoclonal antibodies and convalescent or vaccinee sera raised against the original wild-type virus, and are thus of clinical concern. However, the neutralization potency of two antibodies, 1–57 and 2–7, which target the receptor-binding domain (RBD) of the spike, was unaffected by these emerging strains. Here, we report cryo-EM structures of 1–57 and 2–7 in complex with spike, revealing each of these antibodies to utilize a distinct mechanism to bypass or accommodate RBD mutations. Notably, each antibody represented an immune response with recognition distinct from those of frequent antibody classes. Moreover, many epitope residues recognized by 1–57 and 2–7 were outside hotspots of evolutionary pressure for ACE2 binding and neutralizing antibody escape. We suggest the therapeutic use of antibodies, such as 1–57 and 2–7, which target less prevalent epitopes, could ameliorate issues of monoclonal antibody escape.

show abstract

Potent SARS-CoV-2 neutralizing antibodies directed against spike N-terminal domain target a single supersite

Cited by 512 publications

References 94 publications

mRNA vaccination boosts cross-variant neutralizing antibodies elicited by SARS-CoV-2 infection

mRNA vaccination boosts cross-variant neutralizing antibodies elicited by SARS-CoV-2 infection

Immune response to SARS-CoV-2 variants of concern in vaccinated individuals

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

Contact Info

Product

Resources

About