Cow's Milk Protein Research Articles

Varying Doses of Epicutaneous Immunotherapy With Viaskin Milk vs Placebo in Children With Cow’s Milk Allergy

No approved treatment exists for allergen-specific immunoglobulin E (IgE)-mediated cow's milk allergy (CMA), a common childhood food allergy. To assess dose, efficacy, and safety of epicutaneous immunotherapy with Viaskin milk in children with IgE-mediated CMA. A phase 1/2, 2-part, randomized, double-blind, placebo-controlled dose-ranging clinical trial in children aged 2 to 17 years with IgE-mediated CMA was conducted between November 2014 through December 2017. It took place at 17 trial sites in the US and Canada. Current CMA was confirmed by double-blind, placebo-controlled food challenge at study entry. Part A assessed the short-term safety of 150 μg, 300 μg, or 500 μg of Viaskin milk; part B evaluated the efficacy and safety of the 3 doses vs placebo over 12 months of treatment. Of the 308 screened participants with physician-diagnosed CMA, 198 met eligibility criteria (including an eliciting dose 300 mg or less) and were randomized. Safety of Viaskin milk (150-μg, 300-μg, or 500-μg doses) was evaluated over a 3-week period (part A). In part B, 180 additional participants were randomized to receive Viaskin milk at doses of 150 μg, 300 μg, or 500 μg or placebo (1:1:1:1) for 12 months. The primary outcome was the proportion of treatment responders, defined as a 10-fold or more increase in the cumulative reactive dose of cow's milk protein (reaching at least 144 mg) or a cumulative reactive dose of cow's milk protein at 1444 mg or more at the month 12 double-blind, placebo-controlled food challenge. A total of 95.5% of the randomized participants (mean [SD] age, 8 [4.17] years; 124 of 198 were male [62.6%]) completed treatment. The highest response rate was observed in participants who received Viaskin milk at the 300-μg dose with 24 of 49 responders (49.0%) overall vs 16 of 53 responders (30.2%) in the placebo group (odds ratio, 2.19; 95% CI, 0.91-5.41; P = .09), highest in the 2 to 11 years age group (22 of 38 [57.9%] vs 13 of 40 [32.5%]; P = .04). Most treatment-emergent adverse events were mild or moderate application-site reactions. One participant in the 500-μg Viaskin milk dose group experienced treatment-related anaphylaxis. In this randomized clinical trial, 12 months of daily epicutaneous immunotherapy with a dose of Viaskin milk at 300 μg was associated with a statistically significant treatment response in 2- to 11-year-old children with IgE-mediated CMA. Treatment-related anaphylaxis and treatment-related discontinuation rates were low. Further research is needed to explore Viaskin milk as a viable treatment option for children with IgE-mediated CMA. ClinicalTrials.gov Identifier: NCT02223182.

Amino Acid Composition of Cow's Milk of the North Caucasus Black-and-White Breed

The study of the amino acid composition of dairy raw materials, as shown in numerous studies of domestic and foreign authors, is relevant for conducting breeding work on genetic improvement of dairy, optimizing the system of raising animals of various sex and age groups, including lactating cows to prolong the productive longevity period. The purpose of the research was to study the amino acid composition of the milk of cows of the black-and-white Holsteinized breed, considering genotypic, age-related aspects, as well as with an increase in cow milk protein content. Studies on the composition of amino acids in milk were carried out on cows of a black-and-white breed of a pedigree breeding unit of the Stavropol Territory, the Russian Federation. The obtained results showed that the amino acid content in the black-and-white cow milk in the conditions of the North Caucasus corresponds to the parameters characteristic of the black-and-white Holsteinized breed, while the ratio of essential and interchangeable amino acids, considering age and genetic factors, varies in the range of 0.945-0.951, which is typical for high-quality milk. It was also found that in the process of increasing the protein content of cows by 0.2 abs. percentage from a protein level of 3.10% to 3.30%, a more intensive increase in essential amino acids in relation to interchangeable amino acids is observed, while the ratio of essential to interchangeable amino acids statistically significantly (p<0.05) increased by 1.66%, which is of particular importance for planning measures for the genetic improvement of protein content herds of black-and-white cattle.

To Diet or Not to Diet This Is the Question in Food-Protein-Induced Allergic Proctocolitis (FPIAP)-A Comprehensive Review of Current Recommendations.

Food-protein-induced allergic proctocolitis (FPIAP) is an increasingly reported transient and benign form of colitis that occurs commonly in the first weeks of life in healthy breastfed or formula-fed infants. Distal colon mucosal inflammation is caused by a non-IgE immune reaction to food allergens, more commonly to cow's milk protein. Rectal bleeding possibly associated with mucus and loose stools is the clinical hallmark of FPIAP. To date, no specific biomarker is available, and investigations are reserved for severe cases. Disappearance of blood in the stool may occur within days or weeks from starting the maternal or infant elimination diet, and tolerance to the food allergen is typically acquired before one year of life in most patients. In some infants, no relapse of bleeding occurs when the presumed offending food is reassumed after a few weeks of the elimination diet. Many guidelines and expert consensus on cow's milk allergy have recently been published. However, the role of diet is still debated, and recommendations on the appropriateness and duration of allergen elimination in FPIAP are heterogeneous. This review summarizes and compares the different proposed nutritional management of infants suffering from FPIAP, highlighting the pros and cons according to the most recent literature data.

Growth pattern of paediatric patients affected by cow milk protein allergy fed with rice hydrolyzed formula.

Formulas made from hydrolyzed rice proteins (HRPF) are well-tolerated plant-based alternatives to cow's milk protein (CMP)-based formulas for the dietary management of paediatric patients with CMP allergy (CMPA). Growth in patients with CMPA fed with HRPF has been evaluated in several studies with conflicting results. The aim was to evaluate the growth pattern of children with CMPA over a 12-month follow-up period. Prospective cohort study evaluating growth patterns in challenge proven CMPA paediatric patients receiving HRPF for 12 months. Outcomes were anthropometry (body weight, body length, head circumference), adherence to the study formula and occurrence of adverse events (AEs). Sixty-six children were included and completed the 12-month study. At baseline, all CMPA patients were weaned. For the entire CMPA pediatric patients' cohort, from baseline to the end of the study period, the growth pattern resulted within the normal range of World Health Organization (WHO) growth references. The formula was well tolerated. Adherence was optimal and no AEs related to HRPF use were reported. HRPF is well tolerated and can help support healthy growth and development in infants and young children with CMPA. These type of formula can be given with complementary foods in the dietary management of CMPA.

Effect of maturation at birth on the clinical features of neonatal cow's milk protein allergy: A retrospective study.

Neonatal immune regulation transitions from fetal immunity and varies with maturation status, but its role in neonatal cow's milk protein allergy (CMPA) remains unknown. We studied the association between maturation status at birth and neonatal CMPA. Clinical and laboratory data of neonates presenting with CMPA symptoms were retrospectively collected from two tertiary hospitals. Patients were assessed according to gestational age at birth: preterm, late-preterm, and full-term. Fifty-five infants (26 females, 14 preterm, 15 late-preterm, and 26 full-term) were included; 44 were negative for milk-specific IgE. Neonatal CMPA was common during moderately premature periods. Preterm infants exhibited longer latency from initial CM exposure to disease onset, lower incidence of bloody stool, and absence of elevated monocyte counts. However, immunoreactivity to CM antigens was retained in all infants. Neonatal CMPA features varied with infant maturation status at birth. Our results improve the understanding of intestinal immunity development, fetal/neonatal immune regulation, and CMPA pathogenesis.

In Vitro Digestibility Assessment of Whey from Goat and Camel Milk Fermented with Lactobacillus helveticus for Use as a Base in Formulating Follow-On Formula.

Follow-on formulas are necessary for newborns that are unable to breastfeed. Thus, the development of formulas more tailored to infants' needs is highly important. Recently, using camel milk, goat milk, and sweet milk whey in the formulation of follow-on formulas has gained researchers' attention. Moreover, developing postbiotic systems to create formulas that mimic human milk, are easy to digest, improve compatibility with an infant's gut, and boost immunity is crucial. Thus, this study aimed to create and assess different formulations using fermented whey from camel and goat milks. The fermentation process involved the use of Lactobacillus helveticus as a probiotic and proteolytic lactic acid bacterium strain. The study monitored the proteolytic activity and antioxidant properties of sweet whey produced from cow, camel, and goat milks during the fermentation process with L. helveticus. Also, three different milk fat blends were recombined using edible vegetable oils (coconut oil, rice bran oil, and canola oil) and then they were used to formulate follow-on formulas with a similar fat composition to human milk. Finally, the prepared formulas were tested for their in vitro digestibility and antioxidant activity before and after digestion. The L. helveticus strain had high proteolytic activity towards whey proteins from all the types of milk used in the study. A fermentation time of 6 h produced a higher proteolytic degree and antioxidant activity than 2 and 4 h of fermentation. No significant differences were observed for proteolytic degree and antioxidant activity between 6 and 12 h of fermentation for the cow, camel, and goat whey samples. Regarding the fat blends, animal milk fat, rice bran oil, and canola oil in a fat combination were essential to provide the required amount of unsaturated fatty acids in the follow-on formulas, especially the linoleic acid-α-linolenic acid (LA:ALA) ratio. Adding coconut oil in small amounts to the follow-on formulas provided the required amounts of saturated fatty acids, especially lauric and meristic acids. The follow-on formula based on cow or goat milk whey fermented with L. helveticus released more free amino acids (mmol tyrosine equivalent mL-1) with high levels of antioxidants compared to unfermented ones. The release of free amino acids in the follow-on formula based on camel milk whey was not affected by fermentation. Our results recommend using L. helveticus in the fermentation of follow-on formulas based on camel and goat whey instead of formulas based on cow milk proteins.

Gut microbiota and inflammatory mediators differentiate IgE mediated and non-IgE mediated cases of cow's milk protein at diagnosis.

Analyze fecal and blood samples at point of diagnosis in IgE mediated cow's milk protein allergy (CMPA) and non-IgE mediated (NIM)-CMPA patients to look for potential new biomarkers. Fourteen patients with IgE mediated CMPA and 13 with NIM-CMPA were recruited in three hospitals in the north of Spain, and were compared with 25 infants from a control group of the same age range. To characterize intestinal microbiota, 16S rDNA gene and internal transcribed spaceramplicons of bifidobacteria were sequenced with Illumina technology. Fatty acids were analyzed by gas chromatography, meanwhile intestinal inflammation markers were quantified by enzyme-linked immunosorbent assayand a multiplex system. Immunological analysis of blood was performed by flow cytometry. The fecal results obtained in the NIM-CMPA group stand out. Among them, a significant reduction in the abundance of Bifidobacteriaceae and Bifidobacterium sequences with respect to controls was observed. Bifidobacterial species were also different, highlighting the lower abundance of Bifidobacterium breve sequences. Fecal calprotectin levels were found to be significantly elevated in relation to IgE mediated patients. Also, a higher excretion of IL-10 and a lower excretion of IL-1ra and platelet derived growth factor-BB was found in NIM-CMPA patients. The differential fecal parameters found in NIM-CMPA patients could be useful in the diagnosis of NIM food allergy to CM proteins.

Pepsin-induced hydrolysis and coagulation of proteins in goat, sheep and cow milk

The kinetics of pepsin-induced κ-casein hydrolysis and coagulation in cow, goat, and sheep milk were investigated at 37 °C, pH 6.3 and 6.0. At a 0.1 U mg−1 pepsin-to-κ-casein ratio, sheep milk showed the fastest κ-casein hydrolysis, followed by cow and goat milk as assessed by quantifying the release of para-κ-casein using RP-HPLC. Sheep milk coagulated most rapidly, with κ-casein hydrolysis of 64% and 59% at pH 6.3 and 6.0. Goat milk required higher levels of κ-casein hydrolysis (90% and 86% at pH 6.3 and 6.0), before coagulation could occur. Sheep milk formed denser curds, whereas goat milk curd had a more porous structure. Additionally, small-angle neutron scattering showed differing rates of aggregate size growth among species. These findings indicate κ-casein hydrolysis and coagulation differences are not just due to casein content but also physicochemical characteristics such as casein micelle size. This study deepens our understanding of sheep and goat milk coagulation mechanisms compared to cow milk during the early stages of gastric digestion.

Management of cow's-milk protein allergy in infants and children. What's new in 2023?

The World Allergy Organization Diagnosis and Rationale for Action against Cow's Milk Allergy in 2022 and the European Society of Paediatric Gastroenterology, Hepatology and Nutrition in 2023 updated their guidelines for cow's-milk protein allergy (CMPA) management in infants and children. The objective of this paper is to underline the main points of these new guidelines and debate about some of them.

Epidemiology of food allergy

Food allergy is very common throughout the world and has become a major public health problem, with 220 million people suffering from it. Food allergy has been disproportionately observed in people from industrialized or Western countries and was previously considered to predominate in the pediatric versus adult population. However, the current exponential growth of the adult population and older adults, especially in Western countries, and environmental and lifestyle changes, have profoundly changed the epidemiology of food allergy, with a growing increase even at advanced ages. The foods that represent the greatest severity and clinical impact are peanuts, walnuts, fish, shellfish, eggs, cow's milk protein, wheat, soy and seeds. Although some types of food allergies (cow's milk and egg) may disappear, peanut and tree nut allergies may persist into adulthood. The control or cure of cow's milk protein allergy is gradual throughout childhood and adolescence. Despite the predominance of allergy to fish, shellfish, peanuts, and tree nuts in most reactions in adults, the most common form of IgE-mediated food allergy is oral allergy syndrome or pollen allergy syndrome. food.

Classification of food allergy: generalities

The prevalence of food allergy has increased in some regions of the world, and with it the incidence, according to geographical variability, in the phenotype and clinical manifestations. Food allergy arises from the specific immune response induced by exposure to the proteins of a certain food. Food intolerance refers to non-immune reactions, caused by unique physiological characteristics of the individual, including metabolic, toxic, pharmacological and undefined mechanisms. Adverse reactions to foods are classified as: IgE-mediated: Type I Hypersensitivity, non-IgE-mediated: Type IV Hypersensitivity, mixed: Types I and IV Hypersensitivity Non-Allergic; toxic, pharmacological, metabolic, intolerances. These types of alterations are rare but have increased in recent years; These include protein-induced enterocolitis syndrome, which can cause emesis, diarrhea and hypotension, and shock, which begins two hours after ingestion of the allergen. Protein-induced allergic proctocolitis is a condition that includes allergy to cow's milk protein. Delayed reactions usually affect the digestive system, are more insidious in their onset and are not immediately controlled, even with the suspension of food. There are eight foods responsible for 90% of food allergies: milk, eggs, soy, wheat, peanuts, walnuts, fish, and shellfish.

Navigating formula shortages: associations of parental perspectives on transitioning to alternative infant formulas for cow's milk protein allergy during the 2022 national formula shortage.

The COVID-19 pandemic led to supply chain disruptions causing a severe shortage of infant formula. The shortage impacted parents of infants with cow's milk protein allergy (CMPA) who rely on specialized formulas. However, research on parent perspectives during formula shortages is limited. We aimed to understand the factors guiding parents' decisions when transitioning to alternative amino acid formula (AAF) or extensively hydrolyzed formula (eHF) during the national formula shortage. We conducted a survey using the ZSMoments platform and found that before the shortage, parents valued safety (83%), tolerability (78%), and reputability (78%) as primary factors in selecting eHFs and AAFs. Post-shortage, formula tolerability (86%), assurance (84%), and safety (80%) gained more importance. Among those switching eHF (n = 54), health care provider recommendations (81%), reputability (78%), taste (78%), and tolerability (78%) were rated as "extremely important." Among those switching AAF (n = 26), top factors included tolerability (77%), assurance (73%), safety (73%), cost-effectiveness (73%), and formula trustworthiness (73%). These data suggest that parents carefully weigh various factors when managing their child's CMPA and transitioning to different AAF or eHF options.

Expert consensus on diagnosis and management of neonatal cow's milk protein allergy (2023)

Expert consensus on diagnosis and management of neonatal cow's milk protein allergy (2023)

Influence of lactoferrin and enzymatiс hydrolysates of cow's and mare's milk proteins on anaphylactic sensitivity and cytokine profile of rats

The development of innovative ingredients of specialized formula for children with intolerance to cow's milk proteins requires accounting the influence of the protein component on the allergic sensitivity. The aim of the research was to study the effect of lactoferrin (LF) from cow colostrum, cow's milk protein hydrolysate (CMPH) and mare's milk protein hydrolysate (MMPH) on the severity of the systemic anaphylaxis reaction, the levels of specific IgG antibodies and cytokines in rats parenterally sensitized with ovalbumin (OVA). Material and methods. The experiment was carried out on 4 groups of 26 male Wistar rats, which were sensitized intraperitoneally with chicken egg OVA and a systemic anaphylaxis reaction was induced on the day 29 by intravenous administration of a challenge dose of the antigen (6 mg per kg body weight). LF, CMPH and MMPH were introduced into the diet in doses of 1.4-2 g/kg body weight per day (on an average 1.59±0.04, 1.53±0.05 and 1.48±0.05 g per kg body weight respectively). The content of IgG antibodies in the blood serum was determined by an indirect ELISA; the levels of cytokines IL-1α, IL-1β, IL-2, IL-4, IL-5, IL-6, IL-10, IL-12(p70), IL-13, GM-CSF, IFN-γ and TNF-α were detected by multiplex immunoassay. Results. Dietary LF did not have a significant effect on the severity of active anaphylactic shock (AAS), concentrations of antibodies and cytokines in the blood of animals. As a result of CMPH consumption, there were no significant changes in AAS severity and IgG antibodies to OVA but significant increase in TNF-α level was observed as well as a significant decrease in IL-1α (p<0.05). In animals receiving MMPH, there were also no significant changes in the severity of AAS, but a 1.9-fold decrease in the level of IgG antibodies to OVA (p<0.001) was noticed along with a significant increase in IL-12(p70) (p<0.05) and IL-10 (p<0.10) level. Conclusion. Cosumption of LF by sensitized rats didn't significantly affect their anaphylactic sensitivity and cytokine profile, while CMPH intake induced some signs of pro-inflammatory processes. Consumption of MMPH was accompanied by the formation of an anti-inflammatory cytokine profile, which corresponds to a decrease in the intensity of the humoral immune response to the model allergen. Differences in the effects of two hydrolisates, which have similar degrees of hydrolysis, may be associated with the specific composition of glycopeptides formed during the enzymatic cleavage of milk protein produced by these two species of dairy animals.

Decoding the relationship between cow's milk proteins and development of type 1 diabetes mellitus.

To analyze in silico the evidence of molecular mimicry between human beta-cell autoantigens and cow's milk proteins as a potential type 1 diabetes mellitus (T1DM) trigger. The in silico analysis was performed using bioinformatics tools to compare the amino acid sequences of cow's milk proteins (bovine serum albumin [BSA] and beta-lactoglobulin [BLG]) and human beta-cell autoantigens (glutamic acid decarboxylase-65 [GAD-65], insulin, and zinc transporter 8 [ZnT8]). The structural and functional characteristics of the proteins were analyzed to identify potential molecular mimicry mechanisms. The results of the in silico analysis showed significant sequence similarity between BSA/BLG and GAD-65/human insulin/ZnT8, ranging from 19.64% to 27.27%. The cow's milk proteins evaluated shared structural features with the beta-cell antigens selected for comparison, indicating a potential for molecular mimicry between these proteins. The findings of this study provide further evidence for a potential role of cow's milk proteins in triggering T1DM. The in silico analysis suggests that molecular mimicry mechanisms between cow's milk proteins and human beta-cell antigens may contribute to the autoimmune response leading to T1DM.

Mexican consensus on cow's milk protein allergy.

The aim of this study is to present the current views of a diverse group of experts on the diagnosis and treatment of Cow's Milk Protein Allergy (CMPA) in children under 2 years of age in Mexico. The study, led by a scientific committee of five experts in CMPA, was divided into six phases, including a modified Delphi process. A total of 20 panelists, all of whom were pediatric specialists, participated in administering a comprehensive 38-item questionnaire. The questionnaire was divided into two blocks: Diagnosis and Treatment (20 items each). Consensus was reached on all the proposed items, with an agreement rate of over 70% for each of them. As a result, a diagnostic and treatment algorithm was developed that emphasized the reduction of unnecessary diagnostic studies and encouraged breastfeeding whenever possible. In cases where breast milk is not available, appropriate use of hypoallergenic formulas was recommended. In addition, recommendations on treatment duration and gradual reintroduction of cow's milk protein were provided. The recommendations endorsed by 20 Mexican pediatricians through this study are applicable to everyday clinical practice, thereby enhancing the diagnosis and treatment of children under 2 years of age with CMPA. This, in turn, will foster improved health outcomes and optimize the utilization of healthcare resources.

Allergenicity evaluation of an extensively hydrolyzed infant formula based on cow milk protein.

Cow milk protein allergy (CMPA) is the most common food allergy in infants. Currently, hypoallergenic infant formulas on the market are mainly divided into extensively hydrolyzed whey protein formulas and extensively hydrolyzed casein formulas. There are few extensively hydrolyzed infant formulas (EHFs) with a similar protein composition to breast milk. Therefore, we developed a hypoallergenic infant formula based on extensively hydrolyzed cow milk protein (whey protein-to-casein ratio of 6 : 4) and evaluated its allergenicity in vitro and in vivo. The results showed that the antigenicity of EHF was significantly decreased. The levels of Treg and Th1 cells were increased, while the levels of Th2 cells, IgE and IgG1, plasma histamine and serum mast cell enzymes were significantly decreased. At the same time, the allergic symptoms of the jejunum and lungs of mice were relieved. This study provides a solution for the development of cow milk protein based hypoallergenic infant formulas.

КАЧЕСТВО БЕЛКОВОГО КОМПОНЕНТА МОЛОКА КОРОВ КРАСНО-ПЁСТРОЙ ПОРОДЫ, ПОЛУЧЕННОГО В УСЛОВИЯХ ТЕХНОЛОГИИ ПРИВЯЗНОГО СОДЕРЖАНИЯ

. The uniqueness of milk as a food product lies in the fact that it contains protein, the biological value of which is significantly higher than all known proteins of animal origin. The protein content of milk is under the control of the genotype of cows, but the degree of realization of its achieved potential is influenced by the environmental factor. The red-mottled breed, created in this region, is widely used on traditional dairy farms in the Voronezh Region, characterized by sufficiently high milk productivity and good adaptive properties. In this case, it is relevant to assess the qualitative characteristics of the protein complex of red-mottled cow milk obtained under the conditions of tethered keeping technology, which indicated the purpose of the research. The object of the study were samples of milk from full-aged cows of 5 months of lactation (n = 4) obtained at LLC Bolshevik in the Voronezh region. A sufficiently high concentration of proteins (3.39 ± 0.004 %) was established, the amino acid structure of which is adequate to cow's milk, which indicated their usefulness. The calculated values of amino acid numbers varied in a fairly wide range. The highest amino acid score for all population ages was found in the amino acid complex PH+TYR – 145.8–187.8 %, and the lowest – Met + Cys – 75.2–88.3 %. Amino acids Met + Cys determine the level of bioavailability of cow's milk proteins in the population group "children from 6 months. up to 3 years old", being the first limiting amino acid, up to 75.2 %, and in the group "growing up and children over 3 years old" – up to 88.3 %.

Effect of UHT Thermal Treatment on the Secondary Structures of Milk Proteins: Insights From FTIR Analysis and Potential Allergenic Activity.

Although thermal treatments are beneficial for the preservation and safety of milk, they can also alter its immunogenic activity by affecting its protein components. To achieve precise results, it is essential to identify the specific proteins that cause food allergies. Therefore, investigating the possible alterations of cow's milk proteins (CMPs) resulting from thermal treatments is necessary. In this study, the Fourier transform infrared spectroscopy (FTIR) technique was used to analyze the effect of UHT thermal treatment on the secondary structures of milk casein. Using the second derivative, six characteristic peaks were identified in the Amide I region, ranging from 1700 to 1600 cm-1. It was found that thermal treatments produce shifts in absorption peaks, indicating changes in protein conformation and possibly in allergenic activity. These shifts were clearly identified in the first characteristic peak of samples M8 and M9, from 1621 to 1600 cm-1. The results suggest that thermal treatments may promote protein aggregation by increasing β turns and reducing β sheets and α helices, which could enhance the allergenic potential of the proteins and facilitate the formation of complexes between different milk proteins, such as β-lactoglobulin and κ-casein. Further studies are needed to experimentally validate the allergenic activity of proteins modified by thermal treatments, as only an analytical method (FTIR) was used to evaluate the secondary structures of the proteins.

Blockade of exosome release alleviates the hypersensitive reaction by influencing the T helper cell population in cow's milk allergic mice.

The aim of this work was to evaluate the ameliorative effects of exosome biogenesis in cow's milk allergy (CMA) response. In this context, BALB/c mice were systemically sensitized with cow's milk proteins plus an aluminum adjuvant to induce CMA. The inhibitor GW4869 of exosome biogenesis was added before sensitization and then the anaphylactic reactions were evaluated both in vivo (clinical score and body temperature) and in vitro (serum histamine, allergen-specific antibodies, cytokines by ELISA and cell analysis by flow cytometry) to explore the role of exosomes in the development of CMA. Nanoparticle tracking analysis (NTA) and transmission electron microscopy (TEM) showed that the size distribution and morphology of CMA-derived exosomes were not changed after GW4869 preconditioning, and the concentration of exosomes was much lower than that of the CMA group. In the GW4869 group, inhibition of release of exosomes modulated the induction of T helper 2 cell (Th2)-related substances, with a decrease in histamine and allergen-specific immunoglobulin (Ig) E, and the expression of Th1, Th2, and Th17 cells all decreased as well. Moreover, the experimental data were integrated by means of principal component analysis (PCA) to give an overview that the percentage of Th cells and concentrations of cytokines were more influenced by GW4869 treatment. These data for the first time demonstrated that exosomes are involved in the development of CMA and the blockade of exosome release with GW4869 suppressed the IgE-mediated immune response in CMA.