Multiple SARS-CoV-2 variants escape neutralization by vaccine-induced humoral immunity

García-Beltrán, Wilfredo F.; Lam, Evan C.; Denis, Kerri J St; Nitido, Adam; Garcia, Zeidy H.; Hauser, Blake M.; Feldman, Jared; Pavlovic, Maia; Gregory, David; Poznansky, Mark C.; Sigal, Alex; Schmidt, Aaron; Iafrate, A. John; Naranbhai, Vivek; Balazs, Alejandro B.

doi:10.1016/j.cell.2021.04.006

Cited by 370 publications

(369 citation statements)

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“…Compared with wild type, pseudoviruses with D614G or the mutations defining lineages B.1.1.7, B.1.1.298 and B.1.429 each showed non-statistically significant decreases in neutralization 90 . Lineages P.1 and P.2 each showed significant decreases, with both BNT162b2 (6.7-fold and 5.8-fold, respectively) and mRNA-1273 (4.5-fold and 2.9-fold, respectively) postvaccination sera 90 . The three B.1.351 variants investigated, representing the majority of deposited B.1.351 sequences, showed much larger decreases in neutralization activity, ranging from 34-fold to 42-fold (BNT162b2) and from 19.2-fold to 27.7-fold (mRNA-1273).…”

Section: Vaccine Efficacy Against New Variantsmentioning

confidence: 85%

“…However, one study tested eight SARS-CoV-2 variants of interest or concern, including B.1.1.298, B.1.1.7 and P.1, as well as three B.1.351 variants, distinguished by their combination of NTD mutations, representing sequence diversity in circulating viruses of this lineage. Pseudoviruses were generated by the same system and tested with postvaccination sera from individuals who received two doses of either the BNT162b2 vaccine ( n = 30) or the mRNA-1273 vaccine ( n = 35) 90 . Compared with wild type, pseudoviruses with D614G or the mutations defining lineages B.1.1.7, B.1.1.298 and B.1.429 each showed non-statistically significant decreases in neutralization 90 .…”

Section: Vaccine Efficacy Against New Variantsmentioning

confidence: 99%

“…Pseudoviruses were generated by the same system and tested with postvaccination sera from individuals who received two doses of either the BNT162b2 vaccine ( n = 30) or the mRNA-1273 vaccine ( n = 35) 90 . Compared with wild type, pseudoviruses with D614G or the mutations defining lineages B.1.1.7, B.1.1.298 and B.1.429 each showed non-statistically significant decreases in neutralization 90 . Lineages P.1 and P.2 each showed significant decreases, with both BNT162b2 (6.7-fold and 5.8-fold, respectively) and mRNA-1273 (4.5-fold and 2.9-fold, respectively) postvaccination sera 90 .…”

Section: Vaccine Efficacy Against New Variantsmentioning

confidence: 99%

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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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Section: Vaccine Efficacy Against New Variantsmentioning

confidence: 85%

Section: Vaccine Efficacy Against New Variantsmentioning

confidence: 99%

Section: Vaccine Efficacy Against New Variantsmentioning

confidence: 99%

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

et al. 2021

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“…Variants first isolated in the UK (B.1.1.7 lineage), South Africa (B.1.351) 6 , Brazil (P.1) 2 , South California (B.1.429), New York, (B.1.526), Japan (R.1), Uganda (A.23.1) or the newest emerging variants in India (lineages B.1.617 and B.1.618) share mutations on the spike protein, which have evolved independently. Amongst those, mutations K417E/N/T, L452R, E484K and N501Y are of major concern, as these residues are associated with an enforced receptor binding 7 , and thus increased transmissibility and/or immune escape of the virus 3,8-–11 .…”

Section: Introductionmentioning

confidence: 99%

Ensovibep, a novel trispecific DARPin candidate that protects against SARS-CoV-2 variants

Rothenberger

Walser

Malvezzi

et al. 2021

Preprint

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The SARS-CoV-2 virus responsible for the COVID-19 pandemic has so far infected more than 100 million people globally, and continues to undergo genomic evolution. Emerging SARS-CoV-2 variants show increased infectivity and may lead to resistance against immune responses of previously immunized individuals or existing therapeutics, especially antibody-based therapies. Several monoclonal antibody therapeutics authorized for emergency use or in development start to lose potency against various SARS-CoV-2 variants. Cocktails of two different monoclonal antibodies constitute a promising approach to protect against such variants as long as both antibodies are potent, but come with increased development complexity and therefore cost. As an alternative, we developed two multi-specific DARPin® therapeutics, each combining three independent DARPin® domains binding the SARS-CoV-2 spike protein in one molecule, to potently neutralize the virus and overcome virus escape. Here, we show in a panel of in vitro studies that both multi-specific DARPin® therapeutics, ensovibep (MP0420) and MP0423, are highly potent against the new circulating SARS-CoV-2 variants B.1.1.7 (UK variant) and B.1.351 (South African variant) and the most frequent emerging mutations in the spike protein. Additionally, viral passaging experiments show potent protection by ensovibep and MP0423 against development of escape mutations. Furthermore, we demonstrate that the cooperative binding of the individual modules in a multi-specific DARPin® antiviral is key for potent virus inhibition and protection from escape variants. These results, combined with the relatively small size and high production yields of DARPin® molecules, suggests ensovibep and MP0423 as superior alternatives to monoclonal antibody cocktails for global supply and demonstrate the strength of the DARPin® platform for achieving potent and lasting virus inhibition for SARS-CoV-2 and possibly other viruses.

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“…Currently, several COVID-19 vaccines are in use, and numerous others are in different phases of development. Despite their excellent efficacy and safety profile, the finding that sera from vaccinated individuals showed reduced in vitro neutralization of 5 of 10 pseudoviruses representing circulating SARS-CoV-2 strains is concerning [ 18 ]. Moreover, protection from vaccines may wane and not all people will be able to tolerate the vaccines or mount protective responses.…”

Section: Vaccines For Covid-19: Where Do We Stand?mentioning

confidence: 99%