Abstract
Human clinical trials have shown that a specific partially hydrolyzed 100% whey-based infant formula (pHF-W) reduces AD risk in the first yeast of life. Meta-analyses with a specific pHF-W (pHF-W1) confirm a protective effect while other meta-analyses pooling different pHF-W show conflicting results. Here we investigated the molecular composition and functional properties of the specific pHF-W1 as well as the stability of its manufacturing process over time. This specific pHF-W1 was compared with other pHF-Ws. We used size exclusion chromatography to characterize the peptide molecular weight (MW), a rat basophil degranulation assay to assess the relative level of beta-lactoglobulin (BLG) allergenicity and a preclinical model of oral tolerance induction to test prevention of allergic sensitization. To analyze the exact peptide sequences before and after an HLA binding assay, a mass cytometry approach was used. Peptide size allergenicity and oral tolerance induction were conserved across pHF-W1 batches of production and time. The median MW of the 37 samples of pHF-W1 tested was 800 ± 400 Da. Further oral tolerance induction was observed using 10 different batches of the pHF-W1 with a mean reduction of BLG-specific IgE levels of 0.76 log (95% CI = −0.95; −0.57). When comparing pHF-W1 with three other formulas (pHF-W2 3 and 4), peptide size was not necessarily associated with allergenicity reduction in vitro nor oral tolerance induction in vivo as measured by specific IgE level (p < 0.05 for pHF-W1 and 2 and p = 0.271 and p = 0.189 for pHF-W3 and 4 respectively). Peptide composition showed a limited overlap between the formulas tested ranging from 11.7% to 24.2%. Furthermore nine regions in the BLG sequence were identified as binding HLA-DR. In conclusion, not all pHF-Ws tested have the same peptide size distribution decreased allergenicity and ability to induce oral tolerance. Specific peptides are released during the different processes used by different infant formula producers.
Highlights
Allergies represent a public health concern in numerous countries worldwide [1,2].Food allergies, atopic dermatitis (AD), and respiratory allergies affect an estimated 20%of the global population [1,2]
Size exclusion chromatography (SEC) with UV detection was used to evaluate the peptide molecular weight (MW) distribution in pHF-W, according to the protocol described by Johns et al [20], except for the protein and peptide standards used for MW calibration
We identified that the peptide size distribution thethe formula could notnot predict allergenicity, nor its effect at inducing tolerance
Summary
Allergies represent a public health concern in numerous countries worldwide [1,2].Food allergies, atopic dermatitis (AD), and respiratory allergies affect an estimated 20%of the global population [1,2]. While the etiology of allergic manifestations is still unclear, clinical signs of atopic dermatitis (AD) often predate the development of asthma and 4.0/). Allergic rhinitis later in life, referred to as the atopic march [3,4]. For infants with a family history of allergy and who cannot be exclusively breastfed for the first four to six months, a 100% whey protein-based partially hydrolyzed formula (pHF-W) has been recommended [7,8], as several meta-analyses show a significant decrease in the risk of developing atopic dermatitis in at-risk infants [10,11] and infants from the general population [12] during the first year of life. There are conflicting data in the literature and more well-designed clinical studies are necessary
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