Intestinal helminth infection impairs oral and parenteral vaccine efficacy

The impact of endemic parasitic infection on vaccine efficacy is an important consideration for vaccine development and deployment. We have examined whether intestinal infection with the natural murine helminth Heligmosomoides polygyrus bakeri alters antigen-specific antibody and cellular immune responses to oral and parenteral vaccination in mice. We found that oral vaccination of mice with a clinically relevant, live, attenuated, recombinant Salmonella vaccine that expresses chicken egg ovalbumin ( Salmonella -OVA) disrupts ovalbumin-specific regulatory T cell networks in the gut associated lymphoid tissue and promotes T-effector responses to OVA. Chronic intestinal helminth infection significantly reduced Th1-skewed antibody responses to oral vaccination with Salmonella- OVA. Activated, adoptively-transferred, OVA-specific CD4+ T cells accumulated in draining mesenteric lymph nodes (MLN) of vaccinated mice, irrespective of their helminth-infection status. However, helminth infection increased the frequencies of adoptively-transferred OVA-specific CD4+ T cells producing IL-4 and IL-10 in the MLN. Chronic intestinal helminth infection also significantly reduced Th2-skewed antibody responses to parenteral vaccination with OVA adsorbed to alum. These findings suggest helminth-induced impairment of vaccine antibody responses may be driven by the development of IL-10-secreting CD4+ T regulatory cells. They also underscore the potential need to treat parasitic infection before mass vaccination campaigns in helminth-endemic areas. ### Competing Interest Statement Cathryn R. Nagler is the President and Co-Founder of ClostraBio, Inc. Onyinye Iweala is a consultant for Blueprint Medicines and Novartis. The other authors declare no conflicts of interest. * GALT : gut-associated lymphoid tissue LP : lamina propria MLN : mesenteric lymph node OT-II Tg : OT-II transgenic RAG1 KO : recombination-activating gene 1– deficient Treg : regulatory T cell Teff : T-effector cell WHO : World Health Organization