Evidence map›Paper›PMID 40266063›Full record

ArticleVaccines2025

Sequential SARS-CoV-2 mRNA Vaccination Induces Anti-Idiotype (Anti-ACE2) Antibodies in K18 Human ACE2 Transgenic Mice.

Craig P Collins, Christian Herzog, Logan V Vick, Ryan Nielsen, Yanping Izak Harville, Dan L Longo, John M Arthur, William J Murphy

Abstract read
In one paragraph

Article in Vaccines, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing 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

4 citing papers in PubMed.

  1. Review
  2. Review
  3. Article
  4. Article
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

8 authors.

Craig P CollinsSchool of Medicine, University of California, Davis, CA 95817, USA.
Christian HerzogDepartment of Internal Medicine Nephrology, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA.
Logan V VickSchool of Medicine, University of California, Davis, CA 95817, USA.
Ryan NielsenSchool of Medicine, University of California, Davis, CA 95817, USA.
Yanping Izak HarvilleDepartment of Internal Medicine Nephrology, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA.
Dan L LongoDepartment of Medicine, Harvard Medical School, Boston, MA 02115, USA.
John M ArthurDepartment of Internal Medicine Nephrology, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA.
William J MurphySchool of Medicine, University of California, Davis, CA 95817, USA.

Funding

Immunoregulatory and effector roles of natural killer cell subsetsR01HL140921 · NHLBI · UNIVERSITY OF CALIFORNIA AT DAVIS · PI MURPHY, WILLIAM JOSEPH · 2018 to 2021
$1.9M
NIH HHS R01 HL140921
6 · The paper itself

Abstract

BACKGROUND/

objectivesNovel mRNA vaccines have been successfully utilized to curtail the SARS-CoV-2 pandemic. However, the immunology underlying CoV2 vaccinations, particularly with repeated boosting, has not been properly characterized due to limitations in the preclinical modeling of SARS-CoV-2 infection/vaccinations as well as constantly changing vaccine formulations. The immunoregulatory aspects involved in such vaccine approaches remain unclear. Antibodies, due to inherent immunogenicity by VDJ gene rearrangement, have the potential to induce antibodies directed towards them called anti-idiotype antibodies, which can play a downregulatory role in responses. The paratope of some of these anti-idiotype antibodies can also act as a mirror to the original antigen, which, in the case of SARS-CoV-2 vaccines, would be to the spike protein and, therefore, also be capable of binding its target, ACE2, potentially causing adverse effects.

methodsTo investigate if sequential SARS-CoV-2 mRNA vaccination can induce anti-idiotype antibody responses, K18 hACE2 transgenic mice were serially vaccinated with a SARS-CoV-2 mRNA construct to determine the kinetics of anti-spike and anti-ACE2 responses via custom-made ELISAs.

resultsWhile sequential vaccination produced robust anti-spike responses, anti-ACE2 levels were also detected and gradually amplified with each boost. These anti-ACE2 antibodies persisted for 3 months after the final vaccination and showed evidence of hACE2 binding, as levels were lower in K18 mice in comparison to the wild type.

conclusionsThese data would suggest that sequential SARS-CoV-2 mRNA vaccination has the potential to induce anti-ACE2 antibodies in mice, with each boost amplifying the amount of antibody.

Indexed as

anti-ACE2 antibodiesanti-idiotype antibodiesK18 mouse modelpreclinical SARS-CoV-2 modelingSARS-CoV-2vaccination

Identifiers

PMID40266063
PMCPMC11946769

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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.