Inhibition of cow's milk allergy development in mice by oral delivery of β-lactoglobulin-derived peptides loaded PLGA nanoparticles is associated with systemic whey-specific immune silencing.

Abstract

BACKGROUND:

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-risk non-exclusively breastfed infants. Therefore, safe and effective strategies to improve early life oral tolerance induction may be considered.

OBJECTIVE:

We aim to investigate the efficacy of CMA prevention using oral pre-exposure of two selected 18-AA β-lactoglobulin-derived peptides loaded poly (lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) in a whey-protein induced CMA murine model.

METHODS:

The peptides were loaded in PLGA NPs via a double emulsion solvent evaporation technique. In vivo, 3-week-old female C3H/HeOuJ mice received 6 daily gavages with PBS, whey, Peptide-mix, a high- or low-dose Peptide-NPs or empty-NP plus Peptide-mix, prior to 5 weekly 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-specific serum immunoglobulins and ex vivo whey-stimulated cytokine release by splenocytes was measured.

RESULTS:

Mice pre-treated with high-dose Peptide-NPs but not low-dose or empty-NP plus Peptide-mix, were protected from anaphylaxis and showed a significantly lower acute allergic skin response upon intradermal whey challenge compared to whey-sensitized mice. Compared with the Peptide-mix or empty-NP plus Peptide-mix pre-treatment, the high-dose Peptide-NPs-pre-treatment inhibited ex vivo whey-stimulated pro-inflammatory cytokine TNF-α release by splenocytes.

CONCLUSION & CLINICAL RELEVANCE:

Oral pre-exposure of mice to two β-lactoglobulin-derived peptides loaded PLGA NPs induced a dose-related partial prevention of CMA symptoms upon challenge to whole whey protein and silenced whey-specific systemic immune response. These findings encourage further development of the concept of peptide-loaded PLGA NPs for CMA prevention towards clinical application.

• Authors: Mengshan Liu, Suzan Thijssen, Cornelus F van Nostrum, Wim E Hennink, Johan Garssen, Linette E M Willemsen
• Journal: Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology (Clin Exp Allergy) Vol. 52 Issue 1 Pg. 137-148 (01 2022) ISSN: 1365-2222 [Electronic] England
• PMID: 34145667 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2021 The Authors. Clinical & Experimental Allergy published by John Wiley & Sons Ltd.

Chemical References

• Cytokines
• Lactoglobulins
• Milk Proteins
• Whey Proteins

Topics

• Animals
• Cattle
• Cytokines (metabolism)
• Disease Models, Animal
• Female
• Humans
• Lactoglobulins
• Mice
• Mice, Inbred C3H
• Milk Hypersensitivity
• Milk Proteins
• Nanoparticles
• Whey (metabolism)
• Whey Proteins