Breakthrough infections by SARS-CoV-2 variants boost cross-reactive hybrid immune responses in mRNA-vaccinated Golden Syrian hamsters.

Autor: Diego JG; Infectious and Tropical Diseases Research Group (e-INTRO), Biomedical Research Institute of Salamanca-Research Centre for Tropical Diseases at the University of Salamanca (IBSAL-CIETUS), Faculty of Pharmacy, University of Salamanca, Salamanca, Spain.; Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America.; Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America., Singh G; Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America.; Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America., Jangra S; Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America.; Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America., Handrejk K; Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America.; Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America., Laporte M; Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America.; Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America., Chang LA; Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America.; Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America.; Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America., El Zahed SS; Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America.; Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America., Pache L; NCI Designated Cancer Center, Sanford-Burnham Prebys Medical Discovery Institute, La Jolla, California, United States of America., Chang MW; Department of Medicine, University of California San Diego, La Jolla, California, United States of America., Warang P; Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America.; Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America., Aslam S; Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America.; Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America., Mena I; Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America.; Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America., Webb BT; Department of Veterinary Sciences, University of Wyoming, Laramie, Wyoming, United States of America., Benner C; Department of Medicine, University of California San Diego, La Jolla, California, United States of America., García-Sastre A; Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America.; Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America.; Department of Medicine, Division of Infectious Diseases, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America.; The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America.; Department of Pathology, Molecular and Cell-Based Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America., Schotsaert M; Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America.; Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America.; Icahn Genomics Institute, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America.; Marc and Jennifer Lipschultz Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America.
Jazyk: angličtina
Zdroj: PLoS pathogens [PLoS Pathog] 2024 Jan 10; Vol. 20 (1), pp. e1011805. Date of Electronic Publication: 2024 Jan 10 (Print Publication: 2024).
DOI: 10.1371/journal.ppat.1011805
Abstrakt: Hybrid immunity (vaccination + natural infection) to SARS-CoV-2 provides superior protection to re-infection. We performed immune profiling studies during breakthrough infections in mRNA-vaccinated hamsters to evaluate hybrid immunity induction. The mRNA vaccine, BNT162b2, was dosed to induce binding antibody titers against ancestral spike, but inefficient serum virus neutralization of ancestral SARS-CoV-2 or variants of concern (VoCs). Vaccination reduced morbidity and controlled lung virus titers for ancestral virus and Alpha but allowed breakthrough infections in Beta, Delta and Mu-challenged hamsters. Vaccination primed for T cell responses that were boosted by infection. Infection back-boosted neutralizing antibody responses against ancestral virus and VoCs. Hybrid immunity resulted in more cross-reactive sera, reflected by smaller antigenic cartography distances. Transcriptomics post-infection reflects both vaccination status and disease course and suggests a role for interstitial macrophages in vaccine-mediated protection. Therefore, protection by vaccination, even in the absence of high titers of neutralizing antibodies in the serum, correlates with recall of broadly reactive B- and T-cell responses.
Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: the M.S. laboratory has received unrelated research funding in sponsored research agreements from ArgenX BV, Moderna, 7Hills Pharma and Phio Pharmaceuticals which has no competing interest with this work. The A.G.-S. laboratory has received research support from GSK, Pfizer, Senhwa Biosciences, Kenall Manufacturing, Blade Therapeutics, Avimex, Johnson & Johnson, Dynavax, 7Hills Pharma, Pharmamar, ImmunityBio, Accurius, Nanocomposix, Hexamer, N-fold LLC, Model Medicines, Atea Pharma, Applied Biological Laboratories and Merck, outside of the reported work. A.G.-S. has consulting agreements for the following companies involving cash and/or stock: Castlevax, Amovir, Vivaldi Biosciences, Contrafect, 7Hills Pharma, Avimex, Pagoda, Accurius, Esperovax, Farmak, Applied Biological Laboratories, Pharmamar, CureLab Oncology, CureLab Veterinary, Synairgen, Paratus and Pfizer, outside of the reported work. A.G.-S. has been an invited speaker in meeting events organized by Seqirus, Janssen, Abbott and Astrazeneca. A.G.-S. is inventor on patents and patent applications on the use of antivirals and vaccines for the treatment and prevention of virus infections and cancer, owned by the Icahn School of Medicine at Mount Sinai, New York, outside of the reported work.
(Copyright: © 2024 Diego et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)
Databáze: MEDLINE
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