Intestinal helminth infection impairs vaccine-induced T cell responses and protection against SARS-CoV-2
Desai, P.; Karl, C. E.; Ying, B.; Liang, C.-Y.; Garcia-Salum, T.; Santana, A. C.; Caten, F. T.; Urban, J. F.; Elbashir, S. M.; Edwards, D. K.; Ribeiro, S. P.; Thackray, L. B.; Sekaly, R.-P. K.; Diamond, M. S.
Show abstract
Although vaccines have reduced COVID-19 disease burden, 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 hookworm, on the efficacy of an mRNA vaccine targeting the Wuhan-1 spike protein of SARS-CoV-2. 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 to animals immunized without Hpb infection. Helminth mediated suppression of spike-specific CD8+ T cell responses occurred independently of STAT6 signaling, whereas blockade of IL-10 rescued vaccine-induced CD8+ T cell responses. In mice, intestinal helminth infection impairs vaccine induced T cell responses via an IL-10 pathway and compromises protection against antigenically shifted SARS-CoV-2 variants.
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