Evidence map›Paper›PMID 39353281›Full record

ArticleEBioMedicine2024

Influence of Th1 versus Th2 immune bias on viral, pathological, and immunological dynamics in SARS-CoV-2 variant-infected human ACE2 knock-in mice.

Shailendra Kumar Verma, Fernanda Ana-Sosa-Batiz, Julia Timis, Norazizah Shafee, Erin Maule, Paolla Beatriz Almeida Pinto, Chris Conner, Kristen M Valentine, Dale O Cowley, Robyn Miller and 10 more

Abstract read
In one paragraph

Article in EBioMedicine, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

9 citing papers in PubMed.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

20 authors.

Shailendra Kumar VermaCenter for Vaccine Innovation, La Jolla Institute for Immunology, La Jolla, CA, 92037, USA.
Fernanda Ana-Sosa-BatizCenter for Vaccine Innovation, La Jolla Institute for Immunology, La Jolla, CA, 92037, USA.
Julia TimisCenter for Vaccine Innovation, La Jolla Institute for Immunology, La Jolla, CA, 92037, USA.
Norazizah ShafeeSynbal Inc., 1759 Yorktown Rd., San Mateo, CA, 94402, USA.
Erin MauleCenter for Vaccine Innovation, La Jolla Institute for Immunology, La Jolla, CA, 92037, USA.
Paolla Beatriz Almeida PintoCenter for Vaccine Innovation, La Jolla Institute for Immunology, La Jolla, CA, 92037, USA.
Chris ConnerSynbal Inc., 1759 Yorktown Rd., San Mateo, CA, 94402, USA.
Kristen M ValentineCenter for Vaccine Innovation, La Jolla Institute for Immunology, La Jolla, CA, 92037, USA.
Dale O CowleyTransViragen Inc., 109 Mason Farm Road, Chapel Hill, NC, 27599, USA.
Robyn MillerCenter for Vaccine Innovation, La Jolla Institute for Immunology, La Jolla, CA, 92037, USA.
Annie Elong NgonoCenter for Vaccine Innovation, La Jolla Institute for Immunology, La Jolla, CA, 92037, USA.
Linda TranCenter for Vaccine Innovation, La Jolla Institute for Immunology, La Jolla, CA, 92037, USA.
Krithik VargheseCenter for Vaccine Innovation, La Jolla Institute for Immunology, La Jolla, CA, 92037, USA.
Rúbens Prince Dos Santos AlvesCenter for Vaccine Innovation, La Jolla Institute for Immunology, La Jolla, CA, 92037, USA.
Kathryn M HastieCenter for Vaccine Innovation, La Jolla Institute for Immunology, La Jolla, CA, 92037, USA.
Erica Ollmann SaphireCenter for Vaccine Innovation, La Jolla Institute for Immunology, La Jolla, CA, 92037, USA.
David R WebbSynbal Inc., 1759 Yorktown Rd., San Mateo, CA, 94402, USA.
Kurt JarnaginSynbal Inc., 1759 Yorktown Rd., San Mateo, CA, 94402, USA.
Kenneth KimHistopathology Core Facility, La Jolla Institute for Immunology, La Jolla, CA, 92037, USA. Electronic address: kenneth@lji.org.
Sujan ShrestaCenter for Vaccine Innovation, La Jolla Institute for Immunology, La Jolla, CA, 92037, USA; Division of Host-Microbe Systems and Therapeutics, Department of Pediatrics, UC San Diego School of Medicine, La Jolla, CA, 92037, USA. Electronic address: sujan@lji.org.

Funding

Specific and Broadly Active Monoclonal Antibody Therapeutics Against The FilovirusesU19AI142790 · NIAID · LA JOLLA INSTITUTE FOR IMMUNOLOGY · PI SAPHIRE, ERICA OLLMANN · 2019 to 2023
$40.0M
NIAID NIH HHS U19 AI142790
6 · The paper itself

Abstract

backgroundMouse models that recapitulate key features of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection are important tools for understanding complex interactions between host genetics, immune responses, and SARS-CoV-2 pathogenesis. Little is known about how predominantly cellular (Th1 type) versus humoral (Th2 type) immune responses influence SARS-CoV-2 dynamics, including infectivity and disease course.

methodsWe generated knock-in (KI) mice expressing human ACE2 (hACE2) and/or human TMPRSS2 (hTMPRSS2) on Th1-biased (C57BL/6; B6) and Th2-biased (BALB/c) genetic backgrounds. Mice were infected intranasally with SARS-CoV-2 Delta (B.1.617.2) or Omicron BA.1 (B.1.1.529) variants, followed by assessment of disease course, respiratory tract infection, lung histopathology, and humoral and cellular immune responses.

findingsIn both B6 and BALB/c mice, hACE2 expression was required for infection of the lungs with Delta, but not Omicron BA.1. Disease severity was greater in Omicron BA.1-infected hTMPRSS2-KI and double-KI BALB/c mice compared with B6 mice, and in Delta-infected double-KI B6 and BALB/c mice compared with hACE2-KI mice. hACE2-KI B6 mice developed more severe lung pathology and more robust SARS-CoV-2-specific splenic CD8 T cell responses compared with hACE2-KI BALB/c mice. There were no notable differences between the two genetic backgrounds in plasma cell, germinal center B cell, or antibody responses to SARS-CoV-2.

interpretationSARS-CoV-2 Delta and Omicron BA.1 infection, disease course, and CD8 T cell response are influenced by the host genetic background. These humanized mice hold promise as important tools for investigating the mechanisms underlying the heterogeneity of SARS-CoV-2-induced pathogenesis and immune response.

fundingThis work was funded by NIH U19 AI142790-02S1, the GHR Foundation, the Arvin Gottleib Foundation, and the Overton family (to SS and EOS); Prebys Foundation (to SS); NIH R44 AI157900 (to KJ); and by an American Association of Immunologists Career Reentry Fellowship (FASB).

Indexed as

Angiotensin-Converting Enzyme 2COVID-19Disease Models, AnimalSARS-CoV-2Th1 CellsTh2 CellsAnimalsAntibodies, ViralGene Knock-In TechniquesHumansLungMiceMice, Inbred BALB CMice, Inbred C57BLMice, TransgenicSerine EndopeptidasesACE2 protein, humanAngiotensin-Converting Enzyme 2Antibodies, ViralSerine EndopeptidasesBALB/cB cellsC57BL/6CD4 T cellsCD8 T cellsDeltahACE2hTMPRSS2Mouse modelOmicron BA.1

Identifiers

PMID39353281
PMCPMC11472634

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.