Abstract
Although vaccines have reduced the global COVID-19 disease burden, the impact of gastrointestinal helminth infection on their efficacy in endemic regions of the world remains uncertain. Here, using Heligmosomoides polygyrus bakeri (Hpb), a model, non-invasive murine intestinal hookworm, we evaluated whether Hpb infection affects the efficacy of mRNA S6P, a preclinical vaccine encoding a hexaproline stabilized spike of the Wuhan-1 strain of SARS-CoV-2. In the setting of Hpb infection, immunization of mRNA S6P generated equivalent serum antibody and antigen-specific B cell responses. However, antigen-specific CD4+ and CD8+ T cell responses were reduced compared to mice immunized without Hpb infection. Helminth infection did not skew vaccine-induced T cell responses but rather inhibited their capacity to produce polyfunctional cytokines. Hpb infection caused similar T cell defects in mice immunized with an approved adenoviral vectored SARS-CoV-2 vaccine (Ad26.COV2.S). Challenge experiments showed that although Hpb-infected mice vaccinated with mRNA S6P were fully protected against the ancestral SARS-CoV-2 strain WA1/2020, there was a loss of vaccine-mediated protection against Omicron variant BA5.5 compared to animals immunized in the absence of Hpb infection. These results in mice suggest that intestinal helminth infection can compromise T cell responses and protective efficacy of vaccines against SARS-CoV-2 variants that escape neutralizing antibody responses.
