tetano
Editor, Senior Moderator
J Med Virol
. 2024 Jan;96(1):e29408.
doi: 10.1002/jmv.29408. Th2 and Th17-associated immunopathology following SARS-CoV-2 breakthrough infection in Spike-vaccinated ACE2-humanized mice
Tianyi Zhang[SUP] 1 [/SUP], Nicholas Magazine[SUP] 1 [/SUP], Michael C McGee[SUP] 1 [/SUP], Mariano Carossino[SUP] 1 2 [/SUP], Gianluca Veggiani[SUP] 1 [/SUP], Konstantin G Kousoulas[SUP] 1 [/SUP], Avery August[SUP] 3 [/SUP], Weishan Huang[SUP] 1 3 [/SUP]
Affiliations
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[SUP]+[/SUP] 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.
Keywords: Spike protein vaccine; Th17; Th2; breakthrough infection; eosinophil; pulmonary immunopathology.
. 2024 Jan;96(1):e29408.
doi: 10.1002/jmv.29408. Th2 and Th17-associated immunopathology following SARS-CoV-2 breakthrough infection in Spike-vaccinated ACE2-humanized mice
Tianyi Zhang[SUP] 1 [/SUP], Nicholas Magazine[SUP] 1 [/SUP], Michael C McGee[SUP] 1 [/SUP], Mariano Carossino[SUP] 1 2 [/SUP], Gianluca Veggiani[SUP] 1 [/SUP], Konstantin G Kousoulas[SUP] 1 [/SUP], Avery August[SUP] 3 [/SUP], Weishan Huang[SUP] 1 3 [/SUP]
Affiliations
- PMID: 38258331
- DOI: 10.1002/jmv.29408
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[SUP]+[/SUP] 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.
Keywords: Spike protein vaccine; Th17; Th2; breakthrough infection; eosinophil; pulmonary immunopathology.