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Systemic and mucosal IgA responses are variably induced in response to SARS-CoV-2 mRNA vaccination and are associated with protection against subsequent infection

2022· article· en· W4313428308 on OpenAlexaffabout
Salma Sheikh‐Mohamed, Gary Chao, Baweleta Isho, Michelle Zuo, Carmit Cohen, Yaniv Lustig, Georgie Nahass, Rachel E.A. Salomon, Grace Blacker, Mahya Fazel‐Zarandi, Bhavisha Rathod, Karen Colwill, Alainna Jamal, Zhijie Li, Keelia Quinn deLaunay, Alyson Takaoka, Julia Garnham-Takaoka, Anjali Patel, Christine Fahim, Aimee Patterson, Angel Liu, Nazrana Haq, Shiva Barati, Lois Gilbert, Karen Green, Mohammad Mozafarihashjin, Phillip Samaan, Patrick Budylowski, Walter L. Siqueira, Samira Mubareka, Mario Ostrowski, James M. Rini, Olga L. Rojas, Irving L. Weissman, Michal Caspi Tal, Allison McGeer, Gili Regev, Sharon E. Straus, Anne‐Claude Gingras, Jennifer L. Gommerman

Bibliographic record

VenueThe Journal of Immunology · 2022
Typearticle
Languageen
FieldMedicine
TopicSARS-CoV-2 and COVID-19 Research
Canadian institutionsSunnybrook Health Science CentreUniversity of SaskatchewanCentre for Social InnovationSt. Michael's HospitalSunnybrook HospitalLunenfeld-Tanenbaum Research InstituteUniversity of Toronto
Fundersnot available
KeywordsAntibodyVaccinationImmunologyImmunityImmune systemRespiratory tractHeterologousVirusMucosal immunityBiologyVirologyRespiratory systemMedicineMessenger RNAInternal medicineGene

Abstract

fetched live from OpenAlex

Abstract SARS-CoV-2 is a novel respiratory virus that has quickly spread across the globe. The virus uses a protein called Spike and its associated receptor binding domain (RBD) to interact with angiotensin converting enzyme-2 (ACE-2) on the surface of epithelial cells in the respiratory tract. Although a definite correlate of protection against COVID-19 has yet to emerge, many studies have quantified anti-Spike and anti-RBD IgG antibody (Ab) levels, as well as neutralizing Ab in the blood to ascertain immunity. This approach misses out on Ab that are produced in the upper respiratory tract (URT) mucosa – the site of viral encounter. Whether intramuscularly (i.m.) administered COVID-19 vaccines can promote immunity in the mucosa is not well understood. We recently completed a study where we showed that anti-Spike/RBD IgG could be detected in the saliva following i.m. vaccination with either two doses of mRNA vaccines (Pfizer or Moderna) or with a heterologous dosing of Astra Zeneca followed by an mRNA vaccine. Administration of a second dose of mRNA boosted the IgG but not IgA response, with only 30% of participants remaining positive for IgA at this timepoint. At 6 months post-dose 2, these participants had diminished anti-Spike/RBD IgG levels, although secretory component associated anti-Spike Ab were more stable. Examining two prospective cohorts we found that participants who experienced breakthrough infections with SARS-CoV-2 had lower levels of vaccine-induced serum anti-Spike/RBD IgA at 2–4 weeks post-dose 2 compared to participants who did not experience an infection, whereas IgG levels were comparable between groups. These data suggest that COVID-19 vaccines that elicit a durable IgA response may have utility in preventing infection. We received funding support from CIHR (Fund #15992), a COVID-19 Immunity Task force grant, an “Ontario Together” province of Ontario grant, a CIHR team grant to CoVARR-Net, a Donation from the Royal Bank of Canada (RBC) and a donation from the Krembil Foundation to the Sinai Health System Foundation.

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: Observational · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.002
Threshold uncertainty score0.007

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 head0.044
GPT teacher head0.316
Teacher spread0.272 · 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 designObservational
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

Citations0
Published2022
Admission routes2
Has abstractyes

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