Background: Cow’s milk allergy is the most common cause of clinically relevant adverse reactions to food in infants and children. Partially and extensively hydrolyzed formulae are used for the therapy and prevention of cow’s milk allergy. However, the immunogenic potency of hydrolyzed cow’s milk formulae to induce and/or enhance the allergic phenotype in vivo is still under debate. The aim of this study was to assess the sensitizing capacity and residual allergenicity of various partially and extensively hydrolyzed cow’s milk formulae in a murine model of cow’s milk allergy. Methods: BALB/c mice were immunized with either a cow’s milk formula or various partially and extensively hydrolyzed formulae. Immediate cutaneous hypersensitivity reactions and allergen-specific antibody production were assessed. Results: Although immunization with cow’s milk resulted in 12/13 cases in a positive skin test response to intradermal injection of cow’s milk formulae, only 1 mouse showed a positive skin test to one of the partially hydrolyzed formulae, and none showed positive reactions to other partially hydrolyzed formulae, any of the extensively hydrolyzed formulae, phosphate-buffered saline or the amino acid formula. However, 6 of 8 mice showed positive skin tests when immunized with partially hydrolyzed formulae and with one of the extensively hydrolyzed formulae. Conclusions: The residual allergenic potential is markedly reduced in many hydrolyzed formulae, but most of the formulae investigated could induce an allergic immune response in BALB/c mice. Our murine model seems to be suitable to investigate the sensitizing capacity of hydrolyzed formulae and to differentiate even between extensively hydrolyzed formulae.

Gerrard JW, MacKenzie JWA, Goluboff N, Garson JZ, Maningas CS: Cow’s milk allergy: Prevalence and manifestation in an unselected series of newborns. Acta Paediatr Scand Suppl 1973;234:1–21.
Høst A, Husby S, Østerballe O: A prospective study of cow’s milk allergy in exclusively breast-fed infants. Acta Paediatr Scand 1988;77:663–670.
Jakobsson I, Lindberg T: A prospective study of cow’s milk protein intolerance in Swedish infants. Acta Paediatr Scand 1979;68:853–859.
Høst A, Koletzko B, Dreborg S, Muraro A, Wahn U, Aggett P, Bresson JL, Hernell O, Lafeber H, Michaelsen KF, Micheli JL, Rigo J, Weaver L, Heymans H, Strobel S, Vandenplas Y: Dietary products used in infants for treatment and prevention of food allergy. Arch Dis Child 1999;81:80–84.
Niggemann B, Binder C, Klettke U, Wahn U: In vivo and in vitro studies on the residual allergenicity of partially hydrolysed infant formulae. Acta Paediatr 1999;88:394–398.
Rugo E, Wahl R, Wahn U: How allergenic are hypoallergenic infant formulae? Clin Exp Allergy 1992;22:635–639.
Görtler I, Urbanek R, Forster J: Characterization of antigens and allergens in hypo-allergenic infant formulae. Eur J Pediatr 1995;154:289–294.
Plebani A, Restani P, Naselli A, Galli CL, Meini A, Cavagni G, Ugazio AG, Poiesi C: Monoclonal and polyclonal antibodies against casein components of cow milk for evaluation of residual antigenic activity in ‘hypoallergenic’ infant formulas. Clin Exp Allergy 1997;27:949–956.
Restani P, Plebani A, Velona T, Cavagni G, Ugazio AG, Poiesi C, Muraro A, Galli CL: Use of immunoblotting and monoclonal antibodies to evaluate the residual antigenic activity of milk protein hydrolysed formulae. Clin Exp Allergy 1996;26:1182–1187.
Chirico G, Gasparoni A, Ciardelli L, De Amici M, Colombo A, Rondini G: Immunogenicity and antigenicity of a partially hydrolyzed cow’s milk formula. Allergy 1997;52:82–88.
Szépfalusi Z, Nentwich I, Jost E, Gerstmayr M, Ebner C, Frischer T, Urbanek R: Cord blood mononuclear cells and milk-specific T-cell clones are tools to evaluate the residual immunogenicity of hydrolyzed milk formulas. J Allergy Clin Immun 1998;101:514–520.
Saylor JD, Bahna SL: Anaphylaxis to casein hydrolysate formula. J Pediatr 1991;118:71–74.
Businco L, Cantani A, Longhi A, Giampietro PG: Anaphylactic reactions to a cow’s milk whey protein hydrolysate (Alfa-Ré, Nestlé) in infants with cow’s milk allergy. Ann Allergy 1989;62:333–335.
Nilsson C, Öman H, Halldén G, Lilja G, Lundberg M, Härfast B: A case of allergy to cow’s milk hydrolysate. Allergy 1999;54:1322–1326.
Ragno V, Giampietro PG, Bruno G, Businco L: Allergenicity of milk protein hydrolysate formulae in children with cow’s milk allergy. Eur J Pediatr 1993;152:760–762.
Oldæus G, Anjou K, Björkstén B, Moran JR, Kjellman NIM: Extensively and partially hydrolysed infant formulas for allergy prophylaxis. Arch Dis Child 1997;77:4–10.
Herz U, Braun A, Rückert R, Renz H: Various immunological phenotypes are associated with increased airway responsiveness. Clin Exp Allergy 1998;28:625–634.
Van Halteren AGS, van der Cammen MJF, Biewenga J, Savelkoul HFJ, Kraal G: IgE and mast cell responses on intestinal allergen exposure: A murine model to study the onset of food allergy. J Allergy Clin Immunol 1997;99:94–99.
Byars N, Ferraresi RW: Intestinal anaphylaxis in the rat as a model of food allergy. Clin Exp Immunol 1976;24:352–356.
Li XM, Schofield BH, Huang CK, Kleiner GI, Sampson HA: A murine model of IgE-mediated cow’s milk hypersensitivity. J Allergy Clin Immunol 1999;103:206–214.
Cordle CT, Mahmoud MI, Moore V: Immunogenicity evaluation of protein hydrolysates for hypoallergenic infant formulae. J Pediatr Gastroenterol Nutr 1991;13:270–276.
Cordle CT, Duska-McEwen G, Janas LM, Malone WT, Hirsch MA: Evaluation of the immunogenicity of protein hydrolysate formulas using laboratory animal hyperimmunization. Pediatr Allergy Immunol 1994;5:14–19.
Atkinson HAC, Miller K: Assessment of the brown Norway rat as a suitable model for the investigation of food allergy. Toxicology 1994;91:281–288.
Fritsche R: Induction of oral tolerance to cow’s milk proteins in rats fed with a whey protein hydrolysate. Nutr Res 1998;18:1335–1341.
Poulsen OM, Hau J, Kollerup J: Effect of homogenization and pasteurization on the allergenicity of bovine milk analysed by a murine anaphylactic shock model. Clin Allergy 1987;17:449–458.
Poulsen OM, Hau J: Murine passive cutaneous anaphylaxis test (PCA) for the ‘all or none’ determination of allergenicity of bovine whey proteins and peptides. Clin Allergy 1987;17:75–83.
Ito K, Inagaki-Ohara K, Murosaki S, Nishimura H, Shimokata T, Torii S, Matsuda T, Yoshikai Y: Murine model of IgE production with a predominant Th2-response by feeding protein antigen without adjuvants. Eur J Immunol 1997;27:3427–3437.
Knippels LMJ, van der Kleij HPM, Koppelman SJ, Houben GF, Penninks AH, Felius AA: Comparison of antibody responses to hen’s egg and cow’s milk proteins in orally sensitized rats and food-allergic patients. Allergy 2000;55:251–258.
Poulsen OM, Nielsen BR, Basse A, Hau J: Comparison of intestinal anaphylactic reactions in sensitized mice challenged with untreated bovine milk and homogenized bovine milk. Allergy 1990;45:321–326.
Oldæus G, Björkstén B, Jenmalm MC, Kjellman NIM: Cow’s milk IgE and IgG antibody responses to cow’s milk formulas. Allergy 1999;54:352–357.
Oshiba A, Hamelmann E, Takeda K, Bradley KL, Loader JE, Larsen GL, Gelfand EW: Passive transfer of immediate hypersensitivity and airway hyperresponsiveness by allergen-specific immunoglobulin (Ig) E and IgG1 in mice. J Clin Invest 1996;97:1398–1408.
Oldæus G, Björkstén B, Einarsson R, Kjellman NIM: Antigenicity and allergenicity of cow milk hydrolysates intended for infant feeding. Pediatr Allergy Immunol 1991;4:156–164.
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