Emerging SARS-CoV-2 variants reduce neutralization sensitivity to convalescent sera and monoclonal antibodies

Hu, Jie; Peng, Pai; Wang, Kai; Fang, Liang; Luo, Fei yang; Jin, Ai shun; Liu, Bei zhong; Tang, Ni; Huang, Ailong

doi:10.1038/s41423-021-00648-1

Cited by 103 publications

(80 citation statements)

References 12 publications

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“…ll observed increased entry by pseudoviruses carrying the L452R mutation compared to D614G alone, with a 6.7-to 22.5-fold increase in 293T cells and a 5.8-to 14.7-fold increase in HAOs (Figures 4B and 4C). This increase in pseudovirus infection with the L452R mutation is slightly lower than the increase observed with the N501Y mutation (11.4-to 30.9-fold increase in 293T cells and 23.5-to 37.8-fold increase in HAO relative to D614G alone), which has previously been reported to increase pseudovirus entry (Hu et al, 2021). Pseudoviruses carrying the W152C mutation demonstrated small increases in infection of 293T cells and HAO relative to the D614 control, although these increases were not as pronounced as those observed for the L452R and N501Y pseudoviruses.…”

Section: Increased Transmissibility and Infectivitycontrasting

confidence: 55%

Transmission, infectivity, and neutralization of a spike L452R SARS-CoV-2 variant

Deng

Garcia-Knight

Khalid

et al. 2021

Cell

480

354

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We identified an emerging SARS-CoV-2 variant by viral whole-genome sequencing of 2,172 nasal/nasopharyngeal swab samples from 44 counties in California, a state in the Western United States. Named B.1.427/B.1.429 to denote its 2 lineages, the variant emerged in May 2020 and increased from 0% to >50% of sequenced cases from September 2020 to January 2021, showing 18.6-24% increased transmissibility relative to wild-type circulating strains. The variant carries 3 mutations in the spike protein, including an L452R substitution. We found 2-fold increased B.1.427/B.1.429 viral shedding in vivo and increased L452R pseudovirus infection of cell cultures and lung organoids, albeit decreased relative to pseudoviruses carrying the N501Y mutation common to variants B.1.1.7, B.1.351, and P.1. Antibody neutralization assays revealed 4.0 to 6.7-fold and 2.0-fold decreases in neutralizing titers from convalescent patients and vaccine recipients, respectively. The increased prevalence of a more transmissible variant in California exhibiting decreased antibody neutralization warrants further investigation.

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Section: Increased Transmissibility and Infectivitycontrasting

confidence: 55%

Transmission, infectivity, and neutralization of a spike L452R SARS-CoV-2 variant

Deng

Garcia-Knight

Khalid

et al. 2021

Cell

480

354

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show abstract

“…The B.1.1.7 spike mutations have been shown to diminish neutralization of a higher proportion of NTD-specific neutralizing antibodies (9 of 10; 90%) than RBD-specific neutralizing antibodies (5 of 31; 16%) 63 . Given the immunodominance of the RBD, this could explain the modest reductions in neutralizing activity of convalescent sera against authentic B.1.1.7 or pseudoviruses carrying the B.1.1.7 spike mutations 64 , 65 . The co-occurrence of ΔY144 and E484K is concerning with respect to the polyclonal antibody response as the N3 loop, which ΔY144 changes, is predicted to be among the most immunogenic regions of the spike protein (Fig.…”

Section: Variants Of Interest or Concernmentioning

confidence: 99%

SARS-CoV-2 variants, spike mutations and immune escape

et al. 2021

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Although most mutations in the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genome are expected to be either deleterious and swiftly purged or relatively neutral, a small proportion will affect functional properties and may alter infectivity, disease severity or interactions with host immunity. The emergence of SARS-CoV-2 in late 2019 was followed by a period of relative evolutionary stasis lasting about 11 months. Since late 2020, however, SARS-CoV-2 evolution has been characterized by the emergence of sets of mutations, in the context of ‘variants of concern’, that impact virus characteristics, including transmissibility and antigenicity, probably in response to the changing immune profile of the human population. There is emerging evidence of reduced neutralization of some SARS-CoV-2 variants by postvaccination serum; however, a greater understanding of correlates of protection is required to evaluate how this may impact vaccine effectiveness. Nonetheless, manufacturers are preparing platforms for a possible update of vaccine sequences, and it is crucial that surveillance of genetic and antigenic changes in the global virus population is done alongside experiments to elucidate the phenotypic impacts of mutations. In this Review, we summarize the literature on mutations of the SARS-CoV-2 spike protein, the primary antigen, focusing on their impacts on antigenicity and contextualizing them in the protein structure, and discuss them in the context of observed mutation frequencies in global sequence datasets.

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“…Only N501 and E484 are in proximity of the Fu2 interaction interface. In silico analyses with the PISA server (25) confirmed that the two interfaces do not change in these mutants. Both buried surface areas of the interfaces as well as the number of possible hydrogen bonds remain unchanged (Fig.…”

Section: B1351 Variant Of Concernmentioning

confidence: 84%

“…The newly emerged SARS-CoV-2 B.1.351 variant shows nine amino acid changes in the spike protein. While biological properties of this variant remain to be determined, two amino acid substitutions in the receptor binding motif are of potential concern for vaccine efficacy, neutralization efficiency of existing monoclonal antibody therapies, and altered dynamics of virus spread [23][24][25] . The novel nanobody described here, Fu2, can effectively neutralize the B.1.351 variant and therefore has a strong and unique potential to form the basis for development of therapeutic interventions against this emerging variant of concern.…”

Section: Discussionmentioning

confidence: 99%

A bispecific monomeric nanobody induces spike trimer dimers and neutralizes SARS-CoV-2 in vivo

Hanke

Das

Sheward

et al. 2021

Preprint

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Antibodies binding to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike have therapeutic promise, but emerging variants show the potential for virus escape. Thus, there is a need for therapeutic molecules with distinct and novel neutralization mechanisms. Here we isolated a nanobody that potently neutralizes SARS-CoV-2, including the B.1.351 variant, and cross-neutralizes SARS-CoV. We demonstrate the therapeutic potential of the nanobody in a human ACE2 transgenic mouse model. Using biochemistry and electron cryomicroscopy we show that this nanobody simultaneously interacts with two RBDs from different spike trimers, rapidly inducing the formation of spike trimer-dimers. This naturally elicited bispecific monomeric nanobody establishes a novel strategy for potent immobilization of viral antigens.

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Emerging SARS-CoV-2 variants reduce neutralization sensitivity to convalescent sera and monoclonal antibodies

Cited by 103 publications

References 12 publications

Transmission, infectivity, and neutralization of a spike L452R SARS-CoV-2 variant

Transmission, infectivity, and neutralization of a spike L452R SARS-CoV-2 variant

SARS-CoV-2 variants, spike mutations and immune escape

A bispecific monomeric nanobody induces spike trimer dimers and neutralizes SARS-CoV-2 in vivo

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