{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T12:48:03Z","timestamp":1781786883937,"version":"3.54.5"},"reference-count":45,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2021,7,1]],"date-time":"2021-07-01T00:00:00Z","timestamp":1625097600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004543","name":"China Scholarship Council","doi-asserted-by":"publisher","award":["201707720004"],"award-info":[{"award-number":["201707720004"]}],"id":[{"id":"10.13039\/501100004543","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clin Experimental Allergy"],"published-print":{"date-parts":[[2022,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Two to four percentage of infants are affected by cow's milk allergy (CMA), which persists in 20% of cases. Intervention approaches using early oral exposure to cow's milk protein or hydrolysed cow's milk formula are being studied for CMA prevention. Yet, concerns regarding safety and\/or efficacy remain to be tackled in particular for high\u2010risk non\u2010exclusively breastfed infants. Therefore, safe and effective strategies to improve early life oral tolerance induction may be considered.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objective<\/jats:title><jats:p>We aim to investigate the efficacy of CMA prevention using oral pre\u2010exposure of two selected 18\u2010AA \u03b2\u2010lactoglobulin\u2010derived peptides loaded poly (lactic\u2010co\u2010glycolic acid) (PLGA) nanoparticles (NPs) in a whey\u2010protein induced CMA murine model.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The peptides were loaded in PLGA NPs via a double emulsion solvent evaporation technique. In vivo, 3\u2010week\u2010old female C3H\/HeOuJ mice received 6 daily gavages with PBS, whey, Peptide\u2010mix, a high\u2010 or low\u2010dose Peptide\u2010NPs or empty\u2010NP plus Peptide\u2010mix, prior to 5\u00a0weekly oral sensitizations with cholera toxin plus whey or PBS (sham). One week after the last sensitization, the challenge induced acute allergic skin response, anaphylactic shock score, allergen\u2010specific serum immunoglobulins and ex vivo whey\u2010stimulated cytokine release by splenocytes was measured.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Mice pre\u2010treated with high\u2010dose Peptide\u2010NPs but not low\u2010dose or empty\u2010NP plus Peptide\u2010mix, were protected from anaphylaxis and showed a significantly lower acute allergic skin response upon intradermal whey challenge compared to whey\u2010sensitized mice. Compared with the Peptide\u2010mix or empty\u2010NP plus Peptide\u2010mix pre\u2010treatment, the high\u2010dose Peptide\u2010NPs\u2010pre\u2010treatment inhibited ex vivo whey\u2010stimulated pro\u2010inflammatory cytokine TNF\u2010\u03b1 release by splenocytes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion &amp; Clinical relevance<\/jats:title><jats:p>Oral pre\u2010exposure of mice to two \u03b2\u2010lactoglobulin\u2010derived peptides loaded PLGA NPs induced a dose\u2010related partial prevention of CMA symptoms upon challenge to whole whey protein and silenced whey\u2010specific systemic immune response. These findings encourage further development of the concept of peptide\u2010loaded PLGA NPs for CMA prevention towards clinical application.<\/jats:p><\/jats:sec>","DOI":"10.1111\/cea.13967","type":"journal-article","created":{"date-parts":[[2021,6,18]],"date-time":"2021-06-18T05:29:29Z","timestamp":1623994169000},"page":"137-148","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Inhibition of cow\u2019s milk allergy development in mice by oral delivery of \u03b2\u2010lactoglobulin\u2010derived peptides loaded PLGA nanoparticles is associated with systemic whey\u2010specific immune silencing"],"prefix":"10.1111","volume":"52","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9831-5550","authenticated-orcid":false,"given":"Mengshan","family":"Liu","sequence":"first","affiliation":[{"name":"Division of Pharmaceutics Utrecht Institute for Pharmaceutical Sciences Utrecht University Utrecht The Netherlands"},{"name":"Division of Pharmacology Utrecht Institute for Pharmaceutical Sciences Utrecht University Utrecht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suzan","family":"Thijssen","sequence":"additional","affiliation":[{"name":"Division of Pharmacology Utrecht Institute for Pharmaceutical Sciences Utrecht University Utrecht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cornelus F.","family":"van Nostrum","sequence":"additional","affiliation":[{"name":"Division of Pharmaceutics Utrecht Institute for Pharmaceutical Sciences Utrecht University Utrecht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wim E.","family":"Hennink","sequence":"additional","affiliation":[{"name":"Division of Pharmaceutics Utrecht Institute for Pharmaceutical Sciences Utrecht University Utrecht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johan","family":"Garssen","sequence":"additional","affiliation":[{"name":"Division of Pharmacology Utrecht Institute for Pharmaceutical Sciences Utrecht University Utrecht The Netherlands"},{"name":"Department of Immunology Nutricia Research B.V Utrecht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linette E. 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