Intestinal Helminth Infection Impairs Oral and Parenteral Vaccine Efficacy

作者：Yugen Zhang, LaKeya C. Hardy, Camille M. Kapita, Jason A. Hall, Liubov Arbeeva, Evelyn Campbell, Joseph F. Urban, Yasmine Belkaid, Cathryn R. Nagler, Onyinye I. Iweala · 发表于：The Journal of Immunology · 年份：2023 · DOI：10.4049/jimmunol.2300084 · 被引用次数：10 · 研究领域：Parasites and Host Interactions、Viral gastroenteritis research and epidemiology、Clostridium difficile and Clostridium perfringens research

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 Ag-specific Ab and cellular immune responses to oral and parenteral vaccination in mice. Oral vaccination of mice with a clinically relevant, live, attenuated, recombinant Salmonella vaccine expressing chicken egg OVA (Salmonella-OVA) induced the accumulation of activated, OVA-specific T effector cells rather than OVA-specific regulatory T cells in the GALT. Intestinal helminth infection significantly reduced Th1-skewed Ab responses to oral vaccination with Salmonella-OVA. Activated, adoptively transferred, OVA-specific CD4+ T cells accumulated in draining mesenteric lymph nodes of vaccinated mice, regardless 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 mesenteric lymph node. Ab responses to the oral Salmonella-OVA vaccine were reduced in helminth-free mice adoptively transferred with OVA-specific CD4+ T cells harvested from mice with intestinal helminth infection. Intestinal helminth infection also significantly reduced Th2-skewed Ab responses to parenteral vaccination with OVA adsorbed to alum. These findings suggest that vaccine-specific CD4+ T cells induced in the context of helminth infection retai...