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- Title
Intestinal helminth infection impairs vaccine-induced T cell responses and protection against SARS-CoV-2 in mice.
- Authors
Desai, Pritesh; Karl, Courtney E.; Ying, Baoling; Liang, Chieh-Yu; Garcia-Salum, Tamara; Santana, Ana Carolina; ten-Caten, Felipe; Joseph F.; Elbashir, Sayda M.; Edwards, Darin K.; Ribeiro, Susan P.; Thackray, Larissa B.; Sekaly, Rafick P.; Diamond, Michael S.
- Abstract
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. Editor's summary: Much of the global population lives in areas endemic to helminths, which are known to affect responses to vaccines. To discern how helminth infection affects responses to SARS-CoV-2 vaccines, Desai et al. infected mice with the hookworm Heligmosomoides polygyrus bakeri (Hpb) during the course of a primary SARS-CoV-2 vaccine series. The authors found that Hpb infection compromised T cell, but not antibody, responses to SARS-CoV-2 in an IL-10–dependent manner. Although Hpb-infected K18-hACE2 mice were protected from ancestral SARS-CoV-2 challenge through their antibody responses, they were more susceptible to challenge with an Omicron variant, which can evade antibodies but is still susceptible to T cell responses. Together, these data highlight the need to keep helminth infections in mind during vaccine development and deployment. —Courtney Malo
- Subjects
SARS-CoV-2; SARS-CoV-2 Omicron variant; HELMINTHIASIS; COVID-19 vaccines; T cells
- Publication
Science Translational Medicine, 2024, Vol 16, Issue 761, p1
- ISSN
1946-6234
- Publication type
Article
- DOI
10.1126/scitranslmed.ado1941