Escape of SARS-CoV-2 501Y.V2 from neutralization by convalescent plasma

Cele, Sandile; Gazy, Inbal; Jackson, Laurelle; Hwa, Shi-Hsia; Tegally, Houriiyah; Lustig, Gila; Giandhari, Jennifer; Pillay, Sureshnee; Wilkinson, Eduan; Naidoo, Yeshnee; Karim, Farina; Ganga, Yashica; Khan, Khadija; Bernstein, Mallory; Balazs, Alejandro B.; Gosnell, Bernadett I.; Hanekom, Willem A.; Moosa, Mahomed-Yunus S.; Lessells, Richard J; Oliveira, Túlio de; Sigal, Alex

doi:10.1038/s41586-021-03471-w

Cited by 587 publications

(554 citation statements)

References 28 publications

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“…The results of this study are consistent with previous analyses of the effect of emerging SARS-CoV-2 variants on infection- and vaccine-induced immune responses 5-7 . Indeed, the reductions in neutralisation titres (and by extension, vaccine-induced protection) observed with the 501Y.V2 variant are comparable for leading nucleic acid based COVID-19 vaccines – approximately 4-fold for INO-4800 (Inovio Pharmaceuticals), compared to 6.5-fold for BNT162b2 (BioNTech/Pfizer) and 8.6-fold for mRNA-1273 (Moderna) – and substantially less than the 86-fold reduction reported for AZD1222 (Oxford/AstraZeneca) 5 .…”

Section: Discussionsupporting

confidence: 91%

“…Recent publications have demonstrated that these concerns have some basis, with reduced neutralisation of both the ‘501Y.V1’ variant (also called the ‘UK variant’ or ‘B.1.1.7’) and the ‘501Y.V2’ variant (also called the ‘South African variant’ or ‘B.1.351’) by leading mRNA-based vaccines 5 . Similarly, neutralisation studies using human serum samples from coronavirus disease-19 (COVID-19) patients in South Africa reveal significant decreases in neutralisation efficiency against the 501Y.V2 variant 6,7 .…”

Section: Introductionmentioning

confidence: 99%

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Live Virus Neutralisation of the 501Y.V1 and 501Y.V2 SARS-CoV-2 Variants following INO-4800 Vaccination of Ferrets

Riddell

Goldie

McAuley

et al. 2021

Preprint

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The ongoing COVID-19 pandemic has resulted in significant global morbidity and mortality on a scale similar to the influenza pandemic of 1918. Over the course of the last few months, a number of SARS-CoV-2 variants have been identified against which vaccine-induced immune responses may be less effective. These variants-of-concern have garnered significant attention in the media, with discussion around their impact on the future of the pandemic and the ability of leading COVID-19 vaccines to protect against them effectively. To address concerns about emerging SARS-CoV-2 variants affecting vaccine-induced immunity, we investigated the neutralisation of representative G614, 501Y.V1 and 501Y.V2 virus isolates using sera from ferrets that had received prime-boost doses of the DNA vaccine, INO-4800. Neutralisation titres against G614 and 501Y.V1 were comparable, but titres against the 501Y.V2 variant were approximately 4-fold lower, similar to results reported with other nucleic acid vaccines and supported by in silico biomolecular modelling. The results confirm that the vaccine-induced neutralising antibodies generated by INO-4800 remain effective against current variants-of-concern, albeit with lower neutralisation titres against 501Y.V2 similar to other leading nucleic acid-based vaccines.

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Section: Discussionsupporting

confidence: 91%

Section: Introductionmentioning

confidence: 99%

Live Virus Neutralisation of the 501Y.V1 and 501Y.V2 SARS-CoV-2 Variants following INO-4800 Vaccination of Ferrets

Riddell

Goldie

McAuley

et al. 2021

Preprint

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“…The plasma neutralizing activity of the 13 healthcare workers infected with B.1.1.7 VOC was found to be highest against the homotypic pseudovirus (i.e., B.1.1.7, GMT: 265) and to be reduced to undetectable levels in most cases against the wildtype (D614G) pseudovirus and the other VOC tested, including B.1.427/B.1.429 (Fig. 2 I,L-M) , which is different from what was observed with B.1.351-elicited Abs ( 35 , 36 ). Since B.1.1.7 is now the prevalent lineage in Europe and several other countries( 26 ) the finding that infection with B.1.1.7 elicits a low level of cross-neutralizing Abs towards the other co-circulating lineages is concerning.…”

Section: Resultscontrasting

confidence: 56%

SARS-CoV-2 immune evasion by variant B.1.427/B.1.429

McCallum

Bassi

Marco

et al. 2021

Preprint

152

186

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SARS-CoV-2 entry is mediated by the spike (S) glycoprotein which contains the receptor-binding domain (RBD) and the N-terminal domain (NTD) as the two main targets of neutralizing antibodies (Abs). A novel variant of concern (VOC) named CAL.20C (B.1.427/B.1.429) was originally detected in California and is currently spreading throughout the US and 29 additional countries. It is unclear whether antibody responses to SARS-CoV-2 infection or to the prototypic Wuhan-1 isolate-based vaccines will be impacted by the three B.1.427/B.1.429 S mutations: S13I, W152C and L452R. Here, we assessed neutralizing Ab responses following natural infection or mRNA vaccination using pseudoviruses expressing the wildtype or the B.1.427/B.1.429 S protein. Plasma from vaccinated or convalescent individuals exhibited neutralizing titers, which were reduced 3-6 fold against the B.1.427/B.1.429 variant relative to wildtype pseudoviruses. The RBD L452R mutation reduced or abolished neutralizing activity of 14 out of 35 RBD-specific monoclonal antibodies (mAbs), including three clinical-stage mAbs. Furthermore, we observed a complete loss of B.1.427/B.1.429 neutralization for a panel of mAbs targeting the N-terminal domain due to a large structural rearrangement of the NTD antigenic supersite involving an S13I-mediated shift of the signal peptide cleavage site. These data warrant closer monitoring of signal peptide variants and their involvement in immune evasion and show that Abs directed to the NTD impose a selection pressure driving SARS-CoV-2 viral evolution through conventional and unconventional escape mechanisms.

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“…Poor neutralization activity against the P.1 variant has been reported, mainly related to the E484K mutation alone or in combination with other mutations in the receptor-binding domain, reducing the vaccine efficiency, so fully vaccinated people should be mindful of the potential risk of becoming infected and transmitting the virus to other people [11][12][13].…”

Section: Discussionmentioning

confidence: 99%

Mild Symptomatic SARS-CoV-2 P.1 (B.1.1.28) Infection in a Fully Vaccinated 83-Year-Old Man

Fabiani¹,

Margiotti²,

Viola³

et al. 2021

Pathogens

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The novel severe acute respiratory syndrome coronavirus (SARS-CoV-2) and the associated coronavirus disease 2019 (COVID-19) continue to spread throughout the world, causing more than 120 million infections. Several variants of concern (VOCs) have emerged and spread with implications for vaccine efficacy, therapeutic antibody treatments, and possible reinfections. On 17 March 2021, several VOCs were detected, including lineage B.1.1.7, first identified in the UK, B.1.351 in South Africa, Lineage P.1 (B.1.1.28.1) in Brazil, and novel Sub-Lineage A (A.23.1), reported in Uganda, and B.1.525, reported in Nigeria. Here, we describe an 83-year-old man infected with the SARS-CoV-2 P.1 variant after two doses of the BNT162b2 mRNA COVID-19 vaccine.

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Escape of SARS-CoV-2 501Y.V2 from neutralization by convalescent plasma

Cited by 587 publications

References 28 publications

Live Virus Neutralisation of the 501Y.V1 and 501Y.V2 SARS-CoV-2 Variants following INO-4800 Vaccination of Ferrets

Live Virus Neutralisation of the 501Y.V1 and 501Y.V2 SARS-CoV-2 Variants following INO-4800 Vaccination of Ferrets

SARS-CoV-2 immune evasion by variant B.1.427/B.1.429

Mild Symptomatic SARS-CoV-2 P.1 (B.1.1.28) Infection in a Fully Vaccinated 83-Year-Old Man

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