{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T21:18:32Z","timestamp":1777497512201,"version":"3.51.4"},"reference-count":54,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,12,21]],"date-time":"2021-12-21T00:00:00Z","timestamp":1640044800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>Helminths still infect a quarter of the human population. They manage to establish chronic infections by downmodulating the immune system of their hosts. Consequently, the immune response of helminth-infected individuals to vaccinations may be impaired as well. Here we study the impact of helminth-induced immunomodulation on vaccination efficacy in the mouse system. We have previously shown that an underlying <jats:italic>Litomosoides sigmodontis<\/jats:italic> infection reduced the antibody (Ab) response to anti-influenza vaccination in the context of a systemic expansion of type 1 regulatory T cells (Tr1). Most important, vaccine-induced protection from a challenge infection with the 2009 pandemic H1N1 influenza A virus (2009 pH1N1) was impaired in vaccinated, <jats:italic>L. sigmodontis-<\/jats:italic>infected mice. Here, we aim at the restoration of vaccination efficacy by drug-induced deworming. Treatment of mice with Flubendazole (FBZ) resulted in elimination of viable <jats:italic>L. sigmodontis<\/jats:italic> parasites in the thoracic cavity after two weeks. Simultaneous FBZ-treatment and vaccination did not restore Ab responses or protection in <jats:italic>L. sigmodontis-<\/jats:italic>infected mice. Likewise, FBZ-treatment two weeks prior to vaccination did not significantly elevate the influenza-specific Ig response and did not protect mice from a challenge infection with 2009 pH1N1. Analysis of the regulatory T cell compartment revealed that <jats:italic>L. sigmodontis-<\/jats:italic>infected and FBZ-treated mice still displayed expanded Tr1 cell populations that may contribute to the sustained suppression of vaccination responses in successfully dewormed mice. To outcompete this sustained immunomodulation in formerly helminth-infected mice, we finally combined the drug-induced deworming with an improved vaccination regimen. Two injections with the non-adjuvanted anti-influenza vaccine Begripal conferred 60% protection while MF59-adjuvanted Fluad conferred 100% protection from a 2009 pH1N1 infection in FBZ-treated, formerly <jats:italic>L. sigmodontis-<\/jats:italic>infected mice. Of note, applying this improved prime-boost regimen did not restore protection in untreated <jats:italic>L. sigmodontis-<\/jats:italic>infected mice. In summary our findings highlight the risk of failed vaccinations due to helminth infection.<\/jats:p>","DOI":"10.3389\/fimmu.2021.784141","type":"journal-article","created":{"date-parts":[[2021,12,21]],"date-time":"2021-12-21T04:54:01Z","timestamp":1640062441000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":19,"title":["A Combination of Deworming and Prime-Boost Vaccination Regimen Restores Efficacy of Vaccination Against Influenza in Helminth-Infected Mice"],"prefix":"10.3389","volume":"12","author":[{"given":"Nadine","family":"Stetter","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wiebke","family":"Hartmann","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marie-Luise","family":"Brunn","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stephanie","family":"Stanelle-Bertram","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"G\u00fclsah","family":"Gabriel","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Minka","family":"Breloer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2021,12,21]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1016\/bs.apar.2018.08.001","article-title":"Helminthiasis Epidemiology and Control: Scoring Successes and Meeting the Remaining Challenges","volume":"103","author":"King","year":"2019","journal-title":"Adv Parasitol"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI34261","article-title":"Helminth Infections: The Great Neglected Tropical Diseases","volume":"118","author":"Hotez","year":"2008","journal-title":"J Clin Invest"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2016.07.007","article-title":"Regulation of the Host Immune System by Helminth Parasites","volume":"138","author":"Maizels","year":"2016","journal-title":"J Allergy Clin Immunol"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1111\/all.13944","article-title":"Regulation of Immunity and Allergy by Helminth Parasites","volume":"75","author":"Maizels","year":"2020","journal-title":"Allergy"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1016\/j.imbio.2007.03.009","article-title":"Chronic Helminth Infections Induce Immunomodulation: Consequences and Mechanisms","volume":"212","author":"van Riet","year":"2007","journal-title":"Immunobiology"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2020.06.064","article-title":"Do Parasite Infections Interfere With Immunisation? 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