B.1.526 SARS-CoV-2 variants identified in New York City are neutralized by vaccine-elicited and therapeutic monoclonal antibodies

Zhou, Hao; Dcosta, Belinda M; Samanovic, Marie I.; Mulligan, Mark J.; Landau, Nathaniel R.; Tada, Takuya

doi:10.1101/2021.03.24.436620

Cited by 37 publications

(40 citation statements)

References 36 publications

(33 reference statements)

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“…18 lineages, have shown reduced susceptibility to neutralization from convalescent serum and resistance to monoclonal antibodies. [18][19][20][21][22][23][24][25] Importantly, mutations in the NTD domain, and specifically the neutralization supersite, are extensive in the B.1.351 lineage virus. 18 Using 2 orthogonal pseudovirus neutralization (PsVN) assays based on vesicular stomatitis virus (VSV) and lentivirus expressing S variants, neutralizing capacity of sera from phase 1 participants and non-human primates (NHPs) that received 2 doses of mRNA-1273 was reported.…”

Section: Introductionmentioning

confidence: 99%

Variant SARS-CoV-2 mRNA vaccines confer broad neutralization as primary or booster series in mice

Choi

Koch

et al. 2021

Preprint

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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of a global pandemic that has led to more than 2.8 million deaths worldwide. Safe and effective vaccines are now available, including Moderna's COVID-19 vaccine (mRNA-1273) that showed 94% efficacy in prevention of symptomatic COVID-19 disease in a phase 3 clinical study. mRNA-1273 encodes for a prefusion stabilized full length spike (S) protein of the Wuhan-Hu-1 isolate. However, the emergence of SARS-CoV-2 variants has led to concerns of viral escape from vaccine-induced immunity. Several emerging variants have shown decreased susceptibility to neutralization by vaccine induced immunity, most notably the B.1.351 variant, although the overall impact on vaccine efficacy remains to be determined. Here, we present the initial evaluation in mice of two updated COVID-19 mRNA vaccines designed to target emerging SARS-CoV-2 variants: (1) monovalent mRNA-1273.351 encodes for the S protein found in the B.1.351 lineage and (2) mRNA-1273.211 comprising a 1:1 mix of mRNA-1273 and mRNA-1273.351. Both vaccines were evaluated as a 2-dose primary series in mice; mRNA-1273.351 was also evaluated as a booster dose in animals previously vaccinated with 2-doses of mRNA-1273. The results demonstrated that a primary vaccination series of mRNA-1273.351 was effective at increasing neutralizing antibody titers against the B.1.351 lineage, while mRNA-1273.211 was most effective at providing broad cross-variant neutralization in mice. In addition, these results demonstrated a third dose of mRNA-1273.351 significantly increased both wild-type and B.1.351-specific neutralization titers. Both mRNA-1273.351 and mRNA-1273.211 are currently being evaluated in additional pre-clinical challenge models and in phase 1/2 clinical studies.

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Section: Introductionmentioning

confidence: 99%

Variant SARS-CoV-2 mRNA vaccines confer broad neutralization as primary or booster series in mice

Choi

Koch

et al. 2021

Preprint

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“…E484K has also appeared in VOC-202102-02, a subset of the B.1.1.7 lineage identified in the UK (“SARS-CoV-2 Variants of concern and variants under investigation - GOV.UK,” 2021). The S477N mutation became dominant for periods in Australia (clade 20F) and parts of Europe (20A.EU2), and then appeared in New York in lineage B.1.526 (H. Zhou et al, 2021).…”

Section: Resultsmentioning

confidence: 99%

Effects of common mutations in the SARS-CoV-2 Spike RBD domain and its ligand the human ACE2 receptor on binding affinity and kinetics

Barton

MacGowan

Kutuzov

et al. 2021

Preprint

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The interaction between the SARS-CoV-2 virus Spike protein receptor binding domain (RBD) and the ACE2 cell surface protein is required for viral infection of cells. Mutations in the RBD domain are present in SARS-CoV-2 variants of concern that have emerged independently worldwide. For example, the more transmissible B.1.1.7 lineage has a mutation (N501Y) in its Spike RBD domain that enhances binding to ACE2. There are also ACE2 alleles in humans with mutations in the RBD binding site. Here we perform a detailed affinity and kinetics analysis of the effect of five common RBD mutations (K417N, K417T, N501Y, E484K and S477N) and two common ACE2 mutations (S19P and K26R) on the RBD/ACE2 interaction. We analysed the effects of individual RBD mutations, and combinations found in new SARS-CoV-2 variants first identified in the UK (B.1.1.7), South Africa (B.1.351) and Brazil (P1). Most of these mutations increased the affinity of the RBD/ACE2 interaction. The exceptions were mutations K417N/T, which decreased the affinity. Taken together with other studies, our results suggest that the N501Y and S477N mutations primarily enhance transmission, the K417N/T mutations facilitate immune escape, and the E484K mutation facilitates both transmission and immune escape.

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“…Acquisition of amino acid substitutions in the S RBD-- namely K417N, E484K, and N501Y—and in the NTD, such as L18F, D80A, D215G, and Δ242-244, is associated with increased transmissibility and reduction in neutralization sensitivity 7-17 . Variants containing these substitutions originally isolated in the United Kingdom (UK) (B.1.1.7), Republic of South Africa (B.1.351), Brazil (P.1 lineage), New York (B.1.526), and California (B.1.427/B.1.429), have shown varying reduction in neutralization by convalescent and vaccine serum, and are resistant to some monoclonal antibodies 14,18-24 . Among these variants, B.1.351 contains the most concerning set of mutations in the RBD and NTD subdomains 25 .…”

Section: Introductionmentioning

confidence: 99%

Evaluation of mRNA-1273 against SARS-CoV-2 B.1.351 Infection in Nonhuman Primates

Corbett

Werner

Connell

et al. 2021

Preprint

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Background: Vaccine efficacy against the B.1.351 variant following mRNA-1273 vaccination in humans has not been determined. Nonhuman primates (NHP) are a useful model for demonstrating whether mRNA-1273 mediates protection against B.1.351. Methods: Nonhuman primates received 30 or 100 microgram of mRNA-1273 as a prime-boost vaccine at 0 and 4 weeks, a single immunization of 30 microgram at week 0, or no vaccine. Antibody and T cell responses were assessed in blood, bronchioalveolar lavages (BAL), and nasal washes. Viral replication in BAL and nasal swabs were determined by qRT-PCR for sgRNA, and histopathology and viral antigen quantification were performed on lung tissue post-challenge. Results: Eight weeks post-boost, 100 microgram x2 of mRNA-1273 induced reciprocal ID50 neutralizing geometric mean titers against live SARS-CoV-2 D614G and B.1.351 of 3300 and 240, respectively, and 430 and 84 for the 30 microgram x2 group. There were no detectable neutralizing antibodies against B.1351 after the single immunization of 30 microgram. On day 2 following B.1.351 challenge, sgRNA in BAL was undetectable in 6 of 8 NHP that received 100 microgram x2 of mRNA-1273, and there was a ~2-log reduction in sgRNA in NHP that received two doses of 30 microgram compared to controls. In nasal swabs, there was a 1-log10 reduction observed in the 100 microgram x2 group. There was limited inflammation or viral antigen in lungs of vaccinated NHP post-challenge. Conclusions: Immunization with two doses of mRNA-1273 achieves effective immunity that rapidly controls lower and upper airway viral replication against the B.1.351 variant in NHP.

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B.1.526 SARS-CoV-2 variants identified in New York City are neutralized by vaccine-elicited and therapeutic monoclonal antibodies

Cited by 37 publications

References 36 publications

Variant SARS-CoV-2 mRNA vaccines confer broad neutralization as primary or booster series in mice

Variant SARS-CoV-2 mRNA vaccines confer broad neutralization as primary or booster series in mice

Effects of common mutations in the SARS-CoV-2 Spike RBD domain and its ligand the human ACE2 receptor on binding affinity and kinetics

Evaluation of mRNA-1273 against SARS-CoV-2 B.1.351 Infection in Nonhuman Primates

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