Th2 and Th17-associated immunopathology following SARS-CoV-2 breakthrough infection in Spike-vaccinated ACE2-humanized mice.

Autor: Zhang T; Department of Pathobiological Sciences, Louisiana State University, Baton Rouge, Louisiana, USA., Magazine N; Department of Pathobiological Sciences, Louisiana State University, Baton Rouge, Louisiana, USA., McGee MC; Department of Pathobiological Sciences, Louisiana State University, Baton Rouge, Louisiana, USA., Carossino M; Department of Pathobiological Sciences, Louisiana State University, Baton Rouge, Louisiana, USA.; Louisiana Animal Disease Diagnostic Laboratory, School of Veterinary Medicine, Louisiana State University, Baton Rouge, Louisiana, USA., Veggiani G; Department of Pathobiological Sciences, Louisiana State University, Baton Rouge, Louisiana, USA., Kousoulas KG; Department of Pathobiological Sciences, Louisiana State University, Baton Rouge, Louisiana, USA., August A; Department of Microbiology and Immunology, Cornell University, Ithaca, New York, USA., Huang W; Department of Pathobiological Sciences, Louisiana State University, Baton Rouge, Louisiana, USA.; Department of Microbiology and Immunology, Cornell University, Ithaca, New York, USA.
Jazyk: angličtina
Zdroj: Journal of medical virology [J Med Virol] 2024 Jan; Vol. 96 (1), pp. e29408.
DOI: 10.1002/jmv.29408
Abstrakt: Vaccines have demonstrated remarkable effectiveness in protecting against COVID-19; however, concerns regarding vaccine-associated enhanced respiratory diseases (VAERD) following breakthrough infections have emerged. Spike protein subunit vaccines for SARS-CoV-2 induce VAERD in hamsters, where aluminum adjuvants promote a Th2-biased immune response, leading to increased type 2 pulmonary inflammation in animals with breakthrough infections. To gain a deeper understanding of the potential risks and the underlying mechanisms of VAERD, we immunized ACE2-humanized mice with SARS-CoV-2 Spike protein adjuvanted with aluminum and CpG-ODN. Subsequently, we exposed them to increasing doses of SARS-CoV-2 to establish a breakthrough infection. The vaccine elicited robust neutralizing antibody responses, reduced viral titers, and enhanced host survival. However, following a breakthrough infection, vaccinated animals exhibited severe pulmonary immunopathology, characterized by a significant perivascular infiltration of eosinophils and CD4 + T cells, along with increased expression of Th2/Th17 cytokines. Intracellular flow cytometric analysis revealed a systemic Th17 inflammatory response, particularly pronounced in the lungs. Our data demonstrate that aluminum/CpG adjuvants induce strong antibody and Th1-associated immunity against COVID-19 but also prime a robust Th2/Th17 inflammatory response, which may contribute to the rapid onset of T cell-mediated pulmonary immunopathology following a breakthrough infection. These findings underscore the necessity for further research to unravel the complexities of VAERD in COVID-19 and to enhance vaccine formulations for broad protection and maximum safety.
(© 2024 The Authors. Journal of Medical Virology published by Wiley Periodicals LLC.)
Databáze: MEDLINE
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