2084 Allergenicity assessment of hydrolysed infant formula; A multicenter comparison of a mouse model and a Guinea pig model for cow's milk allergy

Thursday, 15 October 2015
Hall D1 Foyer (Floor 3) (Coex Convention Center)

Betty C.a.m. Van Esch , Utrecht University, Utrecht, Netherlands

Jolanda Van Bilsen, PhD , Tno, Zeist, Netherlands

Prescilla V. Jeurink , Utrecht University, Utrecht, Netherlands

Marjan Gros , Friesland Campina, Wageningen, Netherlands

Johan Garssen, MD, PhD , Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, Netherlands

Joost J Smit, PhD , Institute for Risk Assessment Sciences, Utrecht, Netherlands

Raymond H.H. Pieters , Institute for Risk Assessment Sciences, Utrecht, Netherlands

Leon Knippels, PhD , Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, Netherlands

This study is part of a multi-phase project aiming to validate a mouse model to assess the potential allergenicity of hydrolysed infant formulas. The sensitizing properties of 3 partially hydrolysed whey proteins (pWH-A, -B and -C) were investigated in the mouse model as well as the classically used guinea pig model. Mice and guinea pigs were orally sensitized with whey by gavage or ad libitum via the drinking water respectively. In mice, whey-IgE, acute allergic skin responses, mMCP-1 release, body temperature and anaphylactic shock symptoms were determined upon oral challenge in 4 research centers. In the guinea pigs anaphylactic shock symptoms upon intravenous challenge were measured as a single parameter at 1 center. Elevated levels of whey-specific IgE/IgG1 were detected in whey-sensitized mice in all centers, although the group-average did not reach significance for IgE in center 2.  In contrast to whey-sensitized mice, no acute skin response or mMCP-1 release upon whey challenge was observed in pWH-A-treated mice which corresponded with the absence of anaphylactic shock symptoms in both the mouse and guinea pig model. For pWH-B and pWH-C, that showed positive in the guinea-pig ASA-test, results in mice were inconclusive. None of the centers was able to differentiate between the residual sensitizing capacities of the pWH-B and -C based on a single elicitation parameter and results per center differed. To determine the potential influence of an altered microbiota at the different locations on the sensitizing capacity, an analysis of the microbial composition at the start and end of the study was conducted. Results show that for a well-balanced prediction on the potential allergenicity of hydrolysed infant formulas a multiple parameter model is needed. Therefore, it is concluded that the murine model is suitable to give a safe and nuanced prediction on the allergenicity of pWH’s. A future challenge is to develop an overall scoring system for proper risk assessment, taking all assessed parameters into account.