TY - JOUR
T1 - Intestinal helminth infection impairs vaccine-induced T cell responses and protection against SARS-CoV-2 in mice
AU - Desai, Pritesh
AU - Karl, Courtney E.
AU - Ying, Baoling
AU - Liang, Chieh Yu
AU - Garcia-Salum, Tamara
AU - Santana, Ana Carolina
AU - ten-Caten, Felipe
AU - Urban, Joseph F.
AU - Elbashir, Sayda M.
AU - Edwards, Darin K.
AU - Ribeiro, Susan P.
AU - Thackray, Larissa B.
AU - Sekaly, Rafick P.
AU - Diamond, Michael S.
N1 - Publisher Copyright:
Copyright © 2024 The Authors, some rights reserved
PY - 2024/8/21
Y1 - 2024/8/21
N2 - 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+ and CD8+ 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+ 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+ 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.
AB - 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+ and CD8+ 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+ 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+ 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.
UR - http://www.scopus.com/inward/record.url?scp=85201997984&partnerID=8YFLogxK
U2 - 10.1126/scitranslmed.ado1941
DO - 10.1126/scitranslmed.ado1941
M3 - Article
C2 - 39167662
AN - SCOPUS:85201997984
SN - 1946-6234
VL - 16
JO - Science translational medicine
JF - Science translational medicine
IS - 761
M1 - eado1941
ER -