Escape from neutralizing antibodies by SARS-CoV-2 spike protein variants

By Y. Weisblum, F. Schmidt, Fengwen Zhang, Justin DaSilva, Dan H. Poston, Julio C. C. Lorenzi, Frauke Muecksch, Magda Rutkowska, Hans-Heinrich Hoffmann, E. Michailidis and 14 more. bioRxiv, 2020

1,107 citations recorded by the source corpus.

Neutralizing antibodies elicited by prior infection or vaccination are likely to be key for future protection of individuals and populations against SARS-CoV-2. Moreover, passively administered antibodies are among the most promising therapeutic and prophylactic anti-SARS-CoV-2 agents. However, the degree to which SARS-CoV-2 will adapt to evade neutralizing antibodies is unclear. Using a recombinant chimeric VSV/SARS-CoV-2 reporter virus, we show that functional SARS-CoV-2 S protein variants with mutations in the receptor binding domain (RBD) and N-terminal domain that confer resistance to monoclonal antibodies or convalescent plasma can be readily selected. Notably, SARS-CoV-2 S variants that resist commonly elicited neutralizing antibodies are now present at low frequencies in circulating SARS-CoV-2 populations. Finally, the emergence of antibody-resistant SARS-CoV-2 variants that might limit the therapeutic usefulness of monoclonal antibodies can be mitigated by the use of antibody combinations that target distinct neutralizing epitopes.

Subfields: Infectious Diseases, Radiology, Nuclear Medicine and Imaging

View Paper: https://www.semanticscholar.org/paper/e6ba723e25122d5780de5bdf8e242df0df2844bd

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Infectious Diseases

Citations in the corpus

COVID-19 re-infection by a phylogenetically distinct SARS-coronavirus-2 strain confirmed by whole genome sequencing (2020, background): “Several mutations in the spike protein receptor binding domain and N-terminal domain have been shown to confer reduced susceptibility to neutralizing antibodies [27].”
Nanobody cocktails potently neutralize SARS-CoV-2 D614G N501Y variant and protect mice (2021, positive): “E484K has recently been demonstrated to reduce virus neutralization for several monoclonal antibodies and polyclonal human sera (19 – 21).”
Recurrent deletions in the SARS-CoV-2 spike glycoprotein drive antibody escape (2021, background): “Viruses cultured in vitro in the presence of immune 151 serum have also acquired substitutions in RDR2 that confer neutralization resistance (22).”
Genomics and epidemiology of the P.1 SARS-CoV-2 lineage in Manaus, Brazil (2021, background): “The lineage carries a unique constellation of mutations (table S1), including several that have been previously determined to be of virological importance (6-10) and which are located in the spike protein receptor binding domain (RBD), the region of the virus involved in recognition of the angiotens”
Comprehensive mapping of mutations to the SARS-CoV-2 receptor-binding domain that affect recognition by polyclonal human serum antibodies (2021, background): “This lack of concordance between the epitopes of serum and monoclonal antibodies is consistent with other studies reporting that the specificities of potent monoclonal antibodies often do not recapitulate the sera from which they were isolated (Barnes et al., 2020b; Weisblum et al., 2020).”
Omicron extensively but incompletely escapes Pfizer BNT162b2 neutralization (2021, neutral): “This putative escape mutation 24 , which may confer moderate antibody resistance (https://jbloomlab.github.io/ SARS2_RBD_Ab_escape_maps/escape-calc/), is not found in the majority with two doses of BNT162b2 and previously SARS-CoV-2 infected (blue) or uninfected (orange).”
Complete mapping of mutations to the SARS-CoV-2 spike receptor-binding domain that escape antibody recognition (2020, positive): “In addition, anti-RBD antibodies often dominate the neutralizing activity of the polyclonal antibody response elicited by natural infection (Barnes et al., 2020a; Steffen et al., 2020; Weisblum et al., 2020).”
Neutralizing and protective human monoclonal antibodies recognizing the N-terminal domain of the SARS-CoV-2 spike protein (2021, positive): “(2020) identified an NTD epitope (residues 148 to 151), and mutations in this epitope enabled escape from neutralizing antibody activity in a donor plasma specimen (Weisblum et al., 2020).”
A human coronavirus evolves antigenically to escape antibody immunity (2020, background): “…al., 2020), mutations to the NTD also reduce neutralization by some antibodies and sera (Chi et al., 2020; Kemp et al., 2020; Liu et al., 2020a; McCarthy et al., 2020; Weisblum et al., 2020; Zhou et al., 2019)—and some regions of the NTD undergo significant sequence evolution in 229E (Figure 4A).”
SARS-CoV-2 501Y.V2 escapes neutralization by South African COVID-19 donor plasma (2021, positive): “Indeed, mutations at 484 have been shown to reduce neutralization sensitivity 23,24 .”
Emergence of SARS-CoV-2 B.1.1.7 Lineage — United States, December 29, 2020–January 12, 2021 (2021, background): “A recent case report documented the first case of SARS-CoV-2 reinfection in Brazil with a SARS-CoV-2 variant that contained the E484K mutation,** which has been shown to reduce neutralization by convalescent sera and monoclonal antibodies (9,10).”