Intestinal Helminth Infection Impairs Oral and Parenteral Vaccine Efficacy

To investigate how intestinal helminth infections impact immune responses to oral and parenteral vaccines and to examine the underlying mechanisms of this interplay, particularly in the context of optimizing vaccine efficacy in helminth-endemic populations.The study used a murine model that included mice infected with Heligmosomoides polygyrus bakeri (a murine helminth) or not. The mice were then given oral or parenteral vaccination with a recombinant attenuated Salmonella vaccine expressing chicken egg ovalbumin (OVA).This was a murine model study that used C57BL/6J mice and OT-II transgenic mice. Mice were infected intragastrically with 200 third-stage larvae of Heligmosomoides polygyrus bakeri. Both infected and control mice were then orally vaccinated using a live attenuated recombinant Salmonella vaccine strain (Salmonella-OVA) expressing chicken egg ovalbumin versus an empty vector vaccine (Salmonella-BEM). Mice were also given a parenteral, intramuscular vaccine that consisted of OVA absorbed to alum (OVA-alum). To study cellular immune responses, OVA-specific CD4 + T cells from OT-II transgenic mice were extracted and transferred into recipient mice. Blood and fecal samples were collected to measure OVA-specific antibodies using ELISA.Helminth infection with Heligmosomoides polygyrus bakeri significantly reduced the effectiveness of both oral and parenteral vaccines in mice. Helminth-infected mice had lower Th1 and Th2-skewed responses to both oral (Salmonella-OVA) and parenteral (OVA-alum) vaccines. Helminthic infection increased OVA-specific CD4 + T cells producing IL-4 and IL-10, indicating a shift toward a Th2 and regulatory T cell response, which impairs vaccine efficacy. Despite this, helminth infection did not affect the systemic dissemination of the Salmonella vaccine.Intestinal helminth infections with Heligmosomoides polygyrus bakeri significantly blunt the efficacy of both oral and parenteral vaccines by altering the immune response toward a Th2 and regulatory T cell profile. This impairment suggests that treating helminth infections before vaccination may ensure optimal vaccine efficacy and protect against infectious diseases in endemic regions. The findings underscore the need for integrated health strategies that address parasitic infections to improve global vaccination outcomes.Global vaccination efforts in underserved, low- to middle-income countries face multiple challenges, with vaccine safety and efficacy being paramount. Areas with endemic parasitic infections also need improved vaccine coverage against deadly pathogens such as Salmonella, which can cause typhoid and paratyphoid fever. This study demonstrates that helminth infections impair vaccine-induced immunity in a murine model, highlighting a critical issue for public health initiatives in these regions. The findings suggest that treating helminth infections in endemic regions before vaccination could significantly enhance vaccine efficacy, thereby improving the overall success of vaccination programs and better protecting vulnerable populations.

Authors

Publication Details

Journal
PEDIATRICS
Published
2024-12-01
DOI
https://doi.org/10.1542/peds.2024-069114n
Primary Topic
Clostridium difficile and Clostridium perfringens research
Type
article
Field-Weighted Citation Impact
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article

Intestinal Helminth Infection Impairs Oral and Parenteral Vaccine Efficacy

Christopher C. Parrish, Anna Cheng
PEDIATRICS
Clostridium difficile and Clostridium perfringens research
article

Intestinal Helminth Infection Impairs Oral and Parenteral Vaccine Efficacy

Christopher C. Parrish, Anna Cheng
article en

Abstract

To investigate how intestinal helminth infections impact immune responses to oral and parenteral vaccines and to examine the underlying mechanisms of this interplay, particularly in the context of optimizing vaccine efficacy in helminth-endemic populations.The study used a murine model that included mice infected with Heligmosomoides polygyrus bakeri (a murine helminth) or not. The mice were then given oral or parenteral vaccination with a recombinant attenuated Salmonella vaccine expressing chicken egg ovalbumin (OVA).This was a murine model study that used C57BL/6J mice and OT-II transgenic mice. Mice were infected intragastrically with 200 third-stage larvae of Heligmosomoides polygyrus bakeri. Both infected and control mice were then orally vaccinated using a live attenuated recombinant Salmonella vaccine strain (Salmonella-OVA) expressing chicken egg ovalbumin versus an empty vector vaccine (Salmonella-BEM). Mice were also given a parenteral, intramuscular vaccine that consisted of OVA absorbed to alum (OVA-alum). To study cellular immune responses, OVA-specific CD4 + T cells from OT-II transgenic mice were extracted and transferred into recipient mice. Blood and fecal samples were collected to measure OVA-specific antibodies using ELISA.Helminth infection with Heligmosomoides polygyrus bakeri significantly reduced the effectiveness of both oral and parenteral vaccines in mice. Helminth-infected mice had lower Th1 and Th2-skewed responses to both oral (Salmonella-OVA) and parenteral (OVA-alum) vaccines. Helminthic infection increased OVA-specific CD4 + T cells producing IL-4 and IL-10, indicating a shift toward a Th2 and regulatory T cell response, which impairs vaccine efficacy. Despite this, helminth infection did not affect the systemic dissemination of the Salmonella vaccine.Intestinal helminth infections with Heligmosomoides polygyrus bakeri significantly blunt the efficacy of both oral and parenteral vaccines by altering the immune response toward a Th2 and regulatory T cell profile. This impairment suggests that treating helminth infections before vaccination may ensure optimal vaccine efficacy and protect against infectious diseases in endemic regions. The findings underscore the need for integrated health strategies that address parasitic infections to improve global vaccination outcomes.Global vaccination efforts in underserved, low- to middle-income countries face multiple challenges, with vaccine safety and efficacy being paramount. Areas with endemic parasitic infections also need improved vaccine coverage against deadly pathogens such as Salmonella, which can cause typhoid and paratyphoid fever. This study demonstrates that helminth infections impair vaccine-induced immunity in a murine model, highlighting a critical issue for public health initiatives in these regions. The findings suggest that treating helminth infections in endemic regions before vaccination could significantly enhance vaccine efficacy, thereby improving the overall success of vaccination programs and better protecting vulnerable populations.

PEDIATRICSVol. 154(Supplement 4)
Zero hunger
Openalex Percentile: Top 73%
Clostridium difficile and Clostridium perfringens research
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