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Record W3193567675 · doi:10.1038/s41467-021-25167-5

Two doses of SARS-CoV-2 vaccination induce robust immune responses to emerging SARS-CoV-2 variants of concern

2021· article· en· W3193567675 on OpenAlexfundno aff
Donal Skelly, Adam Harding, Javier Gilbert‐Jaramillo, Michael L. Knight, Stéphanie Longet, Anthony Brown, Sandra Adele, Emily Adland, Helen Brown, Senthil Chinnakannan, Timothy Donnison, Mohammad Ali, Patpong Rongkard, Matthew Pace, Peny Zacharopoulou, Nicola Robinson, Anna Csala, Cathy De Lara, Claire Hutchings, Hema Mehta, Lian Ni Lee, Matthew Edmans, Carl-Philipp Hackstein, Prabhjeet Phalora, Wenqin Li, Eloise Phillips, Tom Malone, Ane Ogbe, Cecilia Jay, Timothy Tipoe, Tom Tipton, Lizzie Stafford, Alexander J. Mentzer, Síle A. Johnson, Ali Amini, Thomas Marjot, Stavros Dimitriadis, Beatrice Simmons, Alexandra Deeks, Sven Kerneis, Hibatullah Abuelgasim, Robert Wilson, Sarah Thomas, Adam Watson, Ahmed Alhussni, Joseph Cutteridge, Esme Weeks, Lucy Denly, Katy Lillie, Jennifer Holmes, Philippa C. Matthews, Denise O’Donnell, Tiong Kit Tan, Lisa Schimanski, Kuan-Ying A. Huang, Pramila Rijal, Lance Turtle, Thushan I. de Silva, Alex Richter, C.J. Duncan, Rebecca Payne, Shona C. Moore, Julian C. Knight, Mark Philip Cassar, Betty Raman, Stefan Neubauer, Anastasia Fries, Nick P. Talbot, Nayia Petousi, Ling‐Pei Ho, Yanchun Peng, Tao Dong, Susana Camara, Spyridoula Marinou, Aline Linder, Syed Adlou, Mwila Kasanyinga, Alice Bridges-Webb, Jennifer Hill, Laura Silva-Reyes, Luke Blackwell, John Frater, Philip Goulder, Christopher P. Conlon, Katie Jeffery, Christina Dold, Andrew J. Pollard, Alex Sigal, Túlio de Oliveira, Alain Townsend, Paul Klenerman, Susanna Dunachie, Eleanor Barnes, Miles W. Carroll, William James

Bibliographic record

VenueNature Communications · 2021
Typearticle
Languageen
FieldMedicine
TopicSARS-CoV-2 and COVID-19 Research
Canadian institutionsnot available
FundersMedical Research CouncilNational Institutes of HealthHamilton Health Sciences FoundationUniversity of OxfordPublic Health EnglandDepartment of Health and Social CareNational Institute for Health and Care ResearchNational Institute for Health Research Health Protection Research UnitUniversity of New South WalesBritish Heart FoundationNIHR Oxford Biomedical Research CentreWellcome TrustBiotechnology and Biological Sciences Research CouncilHuo Family FoundationUK Research and InnovationUK Coronavirus Immunology ConsortiumMeso Scale Diagnostics
KeywordsSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2)Coronavirus disease 2019 (COVID-19)2019-20 coronavirus outbreakSars virusVaccinationVirologyImmune systemBetacoronavirusMedicineCoronavirus InfectionsPandemicImmunologyOutbreakInfectious disease (medical specialty)Disease

Abstract

fetched live from OpenAlex

Abstract Both natural infection with SARS-CoV-2 and immunization with vaccines induce protective immunity. However, the extent to which such immune responses protect against emerging variants is of increasing importance. Such variants of concern (VOC) include isolates of lineage B.1.1.7, first identified in the UK, and B.1.351, first identified in South Africa. Our data confirm that VOC, particularly those with substitutions at residues 484 and 417, escape neutralization by antibodies directed to the ACE2-binding Class 1 and the adjacent Class 2 epitopes but are susceptible to neutralization by the generally less potent antibodies directed to Class 3 and 4 epitopes on the flanks of the receptor-binding domain. To address the potential threat posed by VOC, we sampled a SARS-CoV-2 uninfected UK cohort recently vaccinated with BNT162b2 (Pfizer-BioNTech, two doses delivered 18-28 days apart), alongside a cohort sampled in the early convalescent stages after natural infection in the first wave of the pandemic in Spring 2020. We tested antibody and T cell responses against a reference isolate of the original circulating lineage, B, and the impact of sequence variation in the B.1.1.7 and B.1.351 VOC. Neutralization of the VOC compared to B isolate was reduced, and this was most evident for the B.1.351 isolate. This reduction in antibody neutralization was less marked in post-boost vaccine-induced responses compared to naturally induced immune responses and could be largely explained by the potency of the homotypic antibody response. After a single vaccination, which induced only modestly neutralizing homotypic antibody titres, neutralization against the VOC was completely abrogated in the majority of vaccinees. Importantly, high magnitude T cell responses were generated after two vaccine doses, with the majority of the T cell response directed against epitopes that are conserved between the prototype isolate B and the VOC. These data indicate that VOC may evade protective neutralizing responses induced by prior infection, and to a lesser extent by immunization, particularly after a single vaccine dose, but the impact of the VOC on T cell responses appears less marked. The results emphasize the need to generate high potency immune responses through vaccination in order to provide protection against these and other emergent variants.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.001
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.002
Threshold uncertainty score0.006

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.001
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.001
Insufficient payload (model declined to judge)0.0020.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.127
GPT teacher head0.439
Teacher spread0.312 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designBench or experimental
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations191
Published2021
Admission routes1
Has abstractyes

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