tetano
Editor, Senior Moderator
Sci Transl Med
. 2024 Aug 21;16(761):eado1941.
doi: 10.1126/scitranslmed.ado1941. Epub 2024 Aug 21. Intestinal helminth infection impairs vaccine-induced T cell responses and protection against SARS-CoV-2 in mice
Pritesh Desai[SUP] 1 [/SUP], Courtney E Karl[SUP] 2 [/SUP], Baoling Ying[SUP] 1 [/SUP], Chieh-Yu Liang[SUP] 1 3 [/SUP], Tamara Garcia-Salum[SUP] 4 5 [/SUP], Ana Carolina Santana[SUP] 4 5 [/SUP], Felipe Ten-Caten[SUP] 4 5 [/SUP], Joseph F Urban Jr[SUP] 6 [/SUP], Sayda M Elbashir[SUP] 7 [/SUP], Darin K Edwards[SUP] 7 [/SUP], Susan P Ribeiro[SUP] 4 5 [/SUP], Larissa B Thackray[SUP] 1 [/SUP], Rafick P Sekaly[SUP] 4 5 8 [/SUP], Michael S Diamond[SUP] 1 2 3 9 [/SUP]
Affiliations
Although vaccines have reduced the burden of COVID-19, their efficacy in helminth infection-endemic areas is not well characterized. We evaluated the impact of infection by Heligmosomoides polygyrus bakeri (Hpb), a murine intestinal roundworm, on the efficacy of an mRNA vaccine targeting the Wuhan-1 spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in mice. Although immunization generated similar B cell responses in Hpb-infected and uninfected mice, polyfunctional CD4[SUP]+[/SUP] and CD8[SUP]+[/SUP] T cell responses were markedly reduced in Hpb-infected mice. Hpb-infected and mRNA-vaccinated mice were protected against the ancestral SARS-CoV-2 strain WA1/2020, but control of lung infection was diminished against an Omicron variant compared with animals immunized without Hpb infection. Helminth-mediated suppression of spike protein-specific CD8[SUP]+[/SUP] T cell responses occurred independently of signal transducer and activator of transcription 6 (STAT6) signaling, whereas blockade of interleukin-10 (IL-10) rescued vaccine-induced CD8[SUP]+[/SUP] T cell responses. Together, these data show that, in mice, intestinal helminth infection impaired vaccine-induced T cell responses through an IL-10 pathway, which compromised protection against antigenically drifted SARS-CoV-2 variants.
. 2024 Aug 21;16(761):eado1941.
doi: 10.1126/scitranslmed.ado1941. Epub 2024 Aug 21. Intestinal helminth infection impairs vaccine-induced T cell responses and protection against SARS-CoV-2 in mice
Pritesh Desai[SUP] 1 [/SUP], Courtney E Karl[SUP] 2 [/SUP], Baoling Ying[SUP] 1 [/SUP], Chieh-Yu Liang[SUP] 1 3 [/SUP], Tamara Garcia-Salum[SUP] 4 5 [/SUP], Ana Carolina Santana[SUP] 4 5 [/SUP], Felipe Ten-Caten[SUP] 4 5 [/SUP], Joseph F Urban Jr[SUP] 6 [/SUP], Sayda M Elbashir[SUP] 7 [/SUP], Darin K Edwards[SUP] 7 [/SUP], Susan P Ribeiro[SUP] 4 5 [/SUP], Larissa B Thackray[SUP] 1 [/SUP], Rafick P Sekaly[SUP] 4 5 8 [/SUP], Michael S Diamond[SUP] 1 2 3 9 [/SUP]
Affiliations
- PMID: 39167662
- DOI: 10.1126/scitranslmed.ado1941
Although vaccines have reduced the burden of COVID-19, their efficacy in helminth infection-endemic areas is not well characterized. We evaluated the impact of infection by Heligmosomoides polygyrus bakeri (Hpb), a murine intestinal roundworm, on the efficacy of an mRNA vaccine targeting the Wuhan-1 spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in mice. Although immunization generated similar B cell responses in Hpb-infected and uninfected mice, polyfunctional CD4[SUP]+[/SUP] and CD8[SUP]+[/SUP] T cell responses were markedly reduced in Hpb-infected mice. Hpb-infected and mRNA-vaccinated mice were protected against the ancestral SARS-CoV-2 strain WA1/2020, but control of lung infection was diminished against an Omicron variant compared with animals immunized without Hpb infection. Helminth-mediated suppression of spike protein-specific CD8[SUP]+[/SUP] T cell responses occurred independently of signal transducer and activator of transcription 6 (STAT6) signaling, whereas blockade of interleukin-10 (IL-10) rescued vaccine-induced CD8[SUP]+[/SUP] T cell responses. Together, these data show that, in mice, intestinal helminth infection impaired vaccine-induced T cell responses through an IL-10 pathway, which compromised protection against antigenically drifted SARS-CoV-2 variants.