Intestinal helminth infection impairs vaccine-induced T cell responses and protection against SARS-CoV-2 in mice

• Published in: Science translational medicine Vol. 16; no. 761; p. eado1941
• Main Authors: Desai, Pritesh, Karl, Courtney E, Ying, Baoling, Liang, Chieh-Yu, Garcia-Salum, Tamara, Santana, Ana Carolina, Ten-Caten, Felipe, Joseph F Urban, Jr, Elbashir, Sayda M, Edwards, Darin K, Ribeiro, Susan P, Thackray, Larissa B, Sekaly, Rafick P, Diamond, Michael S
• Format: Journal Article
• Language: English
• Published: United States 21.08.2024
• Subjects: Animals; CD8-Positive T-Lymphocytes - immunology; COVID-19 - immunology; COVID-19 - prevention & control; COVID-19 Vaccines - immunology; Female; Interleukin-10 - metabolism; Mice; Mice, Inbred C57BL; Nematospiroides dubius - immunology; SARS-CoV-2 - immunology; Spike Glycoprotein, Coronavirus - immunology; STAT6 Transcription Factor - metabolism; Strongylida Infections - immunology; T-Lymphocytes - immunology
• ISSN: 1946-6242
• 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 (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.