EP4294214A1 - Milk with a high immunoglobulin content - Google Patents

Abstract

The present invention relates to a process for producing dairy products with a high active immunoglobulin content and a high weight ratio active sIgA / active IgG, involving the steps of collecting mature milk from ruminants with a parity of at least 3, and optionally subjecting said milk to a pasteurization treatment; and to uses of this process. The invention also relates to specific milk products having a high active sIgA / active IgG weight ratio.

Description

MILK WITH A HIGH IMMUNOGLOBULIN CONTENT

The present invention relates to milk and milk-derived products with a high immunoglobulin content and high slgA/lgG weight ratio; and to uses thereof. The invention also relates to processes for providing such milk and milk-derived products.

Milk provides the sole source of nutrition for mammalian offspring until they are able to digest food from other sources. Colostrum (defined as milk obtained within the first 3 days after calving) and milk of all lactating animals contain immunoglobulins (Ig’s), which provide the offspring immunological protection against microbial pathogens and toxins and protect the mammary gland against infections. The major classes of immunoglobulins in milk of various ruminants are IgG, IgA, and IgM, which differ in structure and biological activity. IgG can be subdivided in IgGi and lgG2; IgA can be subdivided in serum IgA and secretory IgA (slgA).

In human breast milk, the major Ig is IgA. Human breast milk contains about 85-90 wt% IgA, about 2-3 wt% IgG, and about 8-10 wt% IgM (J.A. Cakebread et al. , J. Agric. Food Chem., 63 (2015) 7311 -7316).

In ruminant milk, on the other hand, the major Ig is IgG. For instance, in mature bovine milk (defined as bovine milk other than colostrum) about 80 wt% of the Ig’s is IgG (the far majority being IgGi), about 10 wt% is IgM, and about 10 wt% is slgA. The Ig-content in bovine colostrum is much higher than in mature bovine milk: 70-80 wt% of the total protein content of colostrum are Ig’s, whereas in mature bovine milk Ig’s only provide for 1-2 wt% of the total protein content. The IgG/slgA ratio in bovine colostrum is even higher than in mature bovine milk.

There is a continuing desire to produce infant formula which resembles human breast milk as closely as possible. Hence, there is a desire to increase the active immunoglobulin content and/or the active slgA / active IgG ratio of infant formula in order to reach that goal.

Infant formulae are prepared by combining at least one source of whey protein, at least one source of casein protein, at least one source of lipids, at least one carbohydrate source, and vitamins and minerals. Ruminant milk, such as bovine or goat milk, is one of the applied sources of these proteins, carbohydrates, lipids, and vitamins. Suitable whey protein sources - in addition to milk - are whey protein concentrate (WPC) and serum protein concentrate (SPC). These products are the result of separating (skimmed) milk into a casein-rich and a whey protein-rich fraction; either by renneting (i.e. cheese making, leading to cheese whey), acidification (leading to acid whey), or microfiltration (leading to native whey). Immunoglobulins exist in the milk serum phase, instead of the casein micelle phase, and are therefore considered whey proteins.

Whey protein concentrate (WPC) is a product obtained by ultrafiltration and/or reverse osmosis, and optionally demineralization, of acid or cheese whey. By ultrafiltration, a large part of the water, lactose, and ash are removed from the product, thereby concentrating the whey proteins. Reverse osmosis can be used to remove water and to further concentrate the WPC.

Serum protein concentrate (SPC) is also a concentrated whey protein product and differs from WPC in the origin of the whey fraction. Instead of acid or cheese whey, the whey proteins in SPC result from microfiltration of skimmed milk. Said microfiltration results in a concentrated casein retentate fraction and a serum fraction containing most of the whey proteins as the permeate. Conventionally, this permeate fraction is then subjected to ultrafiltration and/or reverse osmosis in order to remove lactose, ash, and water.

In order to preserve food safety and reduce its microbial content, ruminant milk products - such as skimmed milk, WPC, and SPC - have to be heat-treated at least once before consumption and before their use as ingredient in infant formulae. All suitable heat treatments, also the relatively mild ones, negatively affect the active Ig content of the milk; and even more so the active slgA content, since slgA is more heat sensitive than IgG. Hence, heat-treatment will negatively affect the total active Ig content and reduce the active slgA/active IgG ratio. Hence, in order to obtain safe ruminant (e.g. bovine) milk-based food products with a high active total immunoglobulin content and especially a high active slgA content, it is desired to start with raw milk having a total Ig content and slgA/lgG ratio as high as possible.

In order to reach higher Ig contents, it is not an option to use ruminant colostrum instead of or in admixture with mature bovine milk. First of all, the composition of colostrum (e.g. its high concentration of whey proteins) is such that it negatively affects various industrial dairy processing steps: it tends to precipitate on the surface of heat exchangers and evaporators, causing problems in their cleaning and maintenance. In addition, the produced quantities of colostrum are only a fraction of that of normal milk and colostrum is normally not collected from farms. So, using colostrum to adjust Ig levels would cause a significant price increase. Furthermore, at least in the case of bovine products, it would not help in increasing the slgA/lgG ratio because bovine colostrum has an even lower ratio than mature bovine milk.

It is therefore an object of the present invention to provide ruminant mature milk with a high active Ig content and a higher active slgA/active IgG weight ratio than regularly provided mature milk from the same type of ruminant.

It is a further object to provide heat-treated ruminant mature milk with a high active Ig content and a higher weight ratio active slgA/active IgG than regularly provided heat- treated mature milk from the same type of ruminant.

It is a further object to provide a WPC or SPC with a high active Ig content and a higher weight ratio active slgA/active IgG than regularly provided WPC or SPC from the same type of ruminant.

The use of this heat-treated milk, WPC, and/or SPC for producing infant formula results in infant formula with an active slgA/active IgG ratio closer to that of human breast milk.

These objects are met by selecting mature milk from ruminants with a parity of at least 3. Parity, also called lactation number, is the number of times the ruminant has had offspring. Ruminants with a parity of 3 are thus in their third lactation cycle.

The inventors have found that ruminants with a parity of 3 or more have a higher slgA/lgG ratio than the same ruminants with a lower parity.

Accordingly, in one aspect the invention relates to the use of mature milk from ruminants with a parity of at least 3 in a process for producing dairy products with a high active immunoglobulin content and a high weight ratio active slgA / active IgG. In one embodiment, the invention relates to a use of mature milk from ruminants with a parity of at least 3 in a process for producing dairy products with an active immunoglobulin content of at least 418 pg/mL and a weight ratio active slgA / active IgG of at least 0.13, said process involving the steps of collecting mature milk from ruminants with a parity of at least 3, and optionally subjecting said milk to a pasteurization treatment; preferably the active immunoglobulin content is at least 430 pg/mL and the weight ratio active slgA / active IgG is at least 0.14, more preferably the active immunoglobulin content is at least 446 pg/mL and the weight ratio active slgA / active IgG is at least 0.15.

The term “ruminant” includes true ruminants, like cattle, sheep, and goats, and pseudo ruminants, like camels. The preferred ruminants from which milk is selected according to the invention are cattle and goats, meaning that the preferred ruminant milk and ruminant WPC/SPC are bovine milk, bovine WPC, and bovine SPC and goat milk, goat WPC, and goat SPC. The most preferred milk, WPC, and SPC to be produced according to the present invention are bovine milk, bovine WPC, and bovine SPC.

It is known that the total Ig concentration in mature ruminant milk depends on various factors, including lactation stage, breed, age, season, keeping conditions (housing versus grazing), feeding, and parity.

The effect of parity on different Ig ratio’s has also been studied before. For instance, A.J. Guidry and R.H. Miller, J. Dairy Sci. 69 (1986) 1799-1805, reported significant higher IgA and IgM concentrations in bovine milk of lactation number 3 compared to lactation number 1 . But since the IgGi concentration increased in a similar manner, the IgA/lgG weight ratio they reported remained in the range 0.03-0.04, independent of parity - as IgGi is the main component in IgG.

The increase in IgGi as a function of parity was also reported by Liu et al. , The Veterinary Journal 182 (2009) 79-85; whereas J.E. Devery-Pocius and B.L. Larson, J. Dairy Sci. 66 (1983) 221-226, reported that the IgA content in bovine colostrum did not change with age or parity.

Contrary to the finding of Guidry and Miller, data analysis of farm trials has now shown that parity is the most important factor in affecting the slgA/lgG ratio in raw milk.

For instance, regular mature milk collected from healthy Holstein Friesian cows from various farms not selected by parity has a mean slgA/lgG ratio of about 0.13. Selecting the raw milk from healthy cows with a parity of at least 3, resulted in a mean slgA/lgG ratio of at least 0.14, preferably at least 0.15. Upon heat treatment of the milk, the difference between the active slgA/active IgG weight ratios of milk from different parties increases, since slgA is more sensitive to heat treatment than IgG. Healthy ruminants in the present application are defined as ruminants that do not suffer from mastitis. Mastitis results in an increase in Ig’s in the milk; but the milk has low quality. Milk from ruminants having mastitis has a higher somatic cell content. Therefore, the raw milk used in the processes of the present invention has a somatic cell count below 200,000 cells/mL, preferably below 150,000 cells/mL, and most preferably below 100,000 cells/mL as determined by microscopy according to ISO 13366-1 :1977 [Milk - Enumeration of somatic cells - Part 1 : Microscopic method (Reference method); International Organization for Standardization (ISO), Geneva, Switzerland]

The present invention relates to heat-treated mature ruminant milk comprising, after said heat treatment, at least 0.50 g, preferably at least 0.75 g, more preferably at least 0.90, and most preferably at least 1.00 g active immunoglobulins - defined as active slgA + active IgG - per 100 gram protein and a weight ratio active slgA / active IgG of at least 0.13 preferably wherein the heat-treatment is a pasteurisation process.

Active immunoglobulins are immunoglobulins that are in native, i.e. undenatured state. In one embodiment, at least 50 wt% of the total amount of immunoglobulins present in the heat-treated milk is active - i.e. in undenatured state - such as at least 60 wt% or 70 wt%, preferably at least 75 wt%, such as at least 80 wt% or 85 wt%, more preferably at least 90 wt%, even more preferably at least 95 wt%.

The active immunoglobulin content and active slgA / active IgG weight ratio are determined by use of the bovine ELISA quantitation set as described by R. L. Valk- Weeber, T. Eshuis-de Ruiter, L. Dijkhuizen, S.S. van Leeuwen ( International Dairy Journal, Volume 110, November 2020, 104814).

The total protein content in milk can be determined by either the well-known standard Kjeldahl method, with a nitrogen to protein conversion factor of 6.38, or by infrared spectroscopy using Milkoscan™ (complient with ISO 9622:2013). Since the first method is used to calibrate the latter, both methods will result in the same values for the same milk sample.

In order to obtain heat-treated mature ruminant milk with the indicated active slgA and active IgG content and active slgA / active IgG weight ratio, it is first of all important to start with raw milk having a relatively high content of Ig’s; and especially slgA. As mentioned above, slgA is more heat sensitive than IgG and the active slgA/ active IgG ratio thus decreases upon heat treatment.

Starting with a high initial Ig content and in particular a high slgA content thus requires starting from mature milk from ruminants with a parity of at least 3, preferably cows and goats with a parity of at least 3, more preferably cows, with a parity of at least 3.

The subsequent heat treatment, which is required for food safety purposes, should be mild in order to preserve as much active Ig’s - in particular slgA - as possible. The heat treatment according to the present invention is therefore preferably a pasteurization process.

Milk is considered to be pasteurized if it can be classified as “phosphatase-negative” according to the alkaline phosphate test of ISO 118161 IDF 155. Phosphatase is an enzyme that is naturally present in milk, but is destroyed at a temperature just near to the pasteurization temperature. The alkaline phosphatase test is based on the principle that the alkaline phosphatase enzyme in raw milk liberates phenol from a disodium para-nitro phenyl phosphate and forms a yellow coloured complex at alkaline pH. The intensity of the yellow colour is proportional to the activity of the enzyme. The colour intensity is measured by direct comparison with standard colour discs in a Lovibond comparator. Phosphatase-negative is defined as a color intensity corresponding to a phosphatase content below 350U/I.

Various suitable time and temperature combinations can be used to achieve the required pasteurization. Examples of suitable combinations are: 72-75°C for 15-20 seconds, 63-65°C for 30-40 minutes, and 80-85°C for 1-5 seconds.

In a preferred embodiment, the milk is obtained from cows or goats.

Examples of suitable cow breeds are Holstein-Friesian, Holstein, Jersey, Brown Swiss cows, Fleckvieh (Simmental), Montbeliarde, Guernsey, and Ayrshire. The preferred cow breed is Holstein-Friesian.

Examples of suitable goat breeds are Saanen, Nigerian Dwarf, Alpine, Nubian, Anglo- Nubian, Lamancha, Toggenburg, Appenzell, Bunte Deatsche Edelziege, Chamois Colored, Grison Striped, Peacock, and Valais Blackneck. The preferred goat breed is Saanen. The present invention also relates to a whey protein concentrate or serum protein concentrate comprising at least 9 g active immunoglobulins per 100 gram protein and a weight ratio active slgA / active IgG of at least 0.10.

WPC and SPC can be produced with generally known processes, involving ultrafiltration of acid whey, cheese whey, or native whey, an optional demineralization step, concentration, and optionally (spray) drying. During the production, at least one step of reducing the count of micro-organisms, preferably at least one pasteurization step, is conducted: to the milk after skimming and/or before concentration and optional (spray) drying. In order to preserve as much active immunoglobulins as possible, it is desired to limit the number of heating steps, such as pasteurization treatments. In one embodiment, a pasteurization treatment is performed to the milk before separation of the whey/serum fraction.

The heat-treated milk and the whey protein concentrate according to the invention are particularly suitable for use as a nutritional product of as an ingredient of a nutritional composition.

An example of such a nutritional composition is formula milk. The formula milk is selected from the group of infant formulas, follow-up formulas and growing-up formulas (also called young child formulas). Accordingly, the invention further relates to a nutritional composition, typically a nutritional composition for a child, such as formula milk, in particular an infant formula, a follow-up formula, or a growing-up formula. Other examples of nutritional compositions are compositions for adults, such as patients or frail elderly or anyone else desiring to boost their immune system.

Infant formula, baby formula or just formula (American English) or baby milk, infant milk or first milk (British English), is a manufactured food designed and marketed for feeding to babies and infants under 12 months of age, usually prepared for bottle-feeding or cup-feeding from powder (mixed with water) or liquid (with or without additional water). The U.S. Federal Food, Drug, and Cosmetic Act (FFDCA) defines infant formula as "a food which purports to be or is represented for special dietary use solely as a food for infants by reason of its simulation of human milk or its suitability as a complete or partial substitute for human milk". Similarly, the Codex Alimentarius international food standards (WFIO and FAO) defines infant formula as a breast-milk substitute specially manufactured to satisfy, by itself, the nutritional requirements of infants during the first months of life up to the introduction of appropriate complementary feeding. The Codex Alimentarius describes the essential composition of an infant formula with amounts and specifications for the lipid source, protein source, carbohydrate source, vitamins and minerals.

In order to constitute the nutritional composition, in particular the formula milk, the heat- treated milk according to the invention and/or the WPC or SPC according to the invention are combined with at least a lipid source, at least one carbohydrate source, and vitamins and minerals.

In one embodiment, the nutritional composition comprising the heat-treated milk according to the invention and/or the whey protein concentrate and/or serum protein concentrate according to the invention, comprises at least 0.50 g active immunoglobulins per 100 gram protein and a weight ratio active slgA / active IgG of at least 0.10.

In another embodiment, the invention relates to the use of the heat-treated milk according or the invention and/or the whey protein concentrate and/or serum protein concentrate according the invention in a nutritional composition.

The lipid source in the above-mentioned nutritional composition may be any lipid or fat suitable for use in formula milk. Preferred fat sources include milk fat, safflower oil, egg yolk lipid, canola oil, olive oil, coconut oil, palm kernel oil, soybean oil, fish oil, palm oleic, high oleic sunflower oil and high oleic safflower oil, and microbial fermentation oil containing long-chain, polyunsaturated fatty acids. In one embodiment, anhydrous milk fat is used. The lipid source may also be in the form of fractions derived from these oils such as palm olein, medium chain triglycerides, and esters of fatty acids such as arachidonic acid, linoleic acid, palmitic acid, stearic acid, docosahexaenoic acid, linolenic acid, oleic acid, lauric acid, capric acid, caprylic acid, caproic acid, and the like. Small amounts of oils containing high quantities of preformed arachidonic acid and docosahexaenoic acid such as fish oils or microbial oils may be added. The fat source preferably has a ratio of n-6 to n-3 fatty acids of about 5:1 to about 15:1 ; for example about 8:1 to about 10:1. In a specific aspect, the infant formula comprises an oil mix comprising palmitic acid esterified to triacylglycerols, for example wherein the palmitic acid esterified in the sn-2 position of triacylglycerol is in the amount from 10% to 60% by weight of total palmitic acid and palmitic acid esterified in the sn-1/sn-3 position of triacylglycerol is in the amount of from 30% to 80% by weight of total palmitic acid.

Examples of vitamins and minerals that are preferably present in formula milk are vitamin A, vitamin B1 , vitamin B2, vitamin B6, vitamin B12, vitamin E, vitamin K, vitamin C, vitamin D, folic acid, inositol, niacin, biotin, pantothenic acid, choline, calcium, phosphorous, iodine, iron, magnesium, copper, zinc, manganese, chloride, potassium, sodium, selenium, chromium, molybdenum, taurine, and L-carnitine. Minerals are usually added in salt form.

Examples of carbohydrates that are preferably present in formula milk are lactose, non- digestible oligosaccharides such as galacto-oligosaccharides (GOS), fructo- oligosaccharides (FOS), inulin, xylo-oligosaccharides, and human milk oligosaccharides (HMOs). Suitable HMOs include 2 -FL, 3’-GL, 3’-SL, 6’-SL, LNT, LNnT, and combinations thereof. FIMO’s are commercially available or can be isolated from milk in particular from human breast milk.

If necessary, the nutritional composition may contain emulsifiers and stabilisers such as soy lecithin, citric acid esters of mono- and di-glycerides, and the like. It may also contain other substances which may have a beneficial effect such as lactoferrin, nucleotides, nucleosides, probiotics, and the like.

Suitable probiotics include Lactobacteria, Bifidobacterium lactis such as Bifidobacterium lactis Bb12, Streptococcus thermophilus, Lactobacillus johnsonii La1, Bifidobacterium longum BL999, Lactobacillus rhamnosus LPR, L rhamnosus GG, Lactobacillus reuteri, Lactobacillus salivarius. Such prebiotics are commercially available.

Formula milk is generally available as a spray-dried powder. Spray-drying involves an additional heating step. In order to preserve as much of the active immunoglobulins, in particular active IgA, it is desired to keep the heating conditions during spray-drying as mild as possible. If a dairy product according to the invention e.g. a WPC or SPC, is used for producing the nutritional composition of the present invention, it is preferably either dry blended with the other ingredients or mixed as liquid WPC or liquid SPC with other liquid ingredients; all in order to the reduce the number of heat treatments that may negatively affect the immunoglobulin content. EXAMPLES

Example 1

Raw milk samples were collected from 1998 cows on 21 Dutch farms. The cows were not suffering from mastitis and hence the milk had a somatic cell count below 200,000 cells/mL. Fresh milk samples were analyzed for their protein content; stored frozen samples were used for analysis of active IgG and active slgA content. The protein content was measured by infrared spectroscopy using a MilkoScan™ (ISO 9622, Qlip, Zutphen, the Netherlands). Contents of active IgG and active slgA were measured using the quantitative ELISA method as described by R. L. Valk-Weebera, T. Eshuis - de Ruiter, L. Dijkhuizen, S.S. van Leeuwen {International Dairy Journal, Volume 110, November 2020, 104814).

Table 1 shows the mean active Ig and total protein contents, per parity class and for the overall population not selected on parity.

Table 1 - Raw milk data

Example 2

The milk samples listed in Table 1 were pasteurized under standard pasteurization conditions: 75°C, 20 seconds. Table 2 shows the active slgA and active IgG levels and the weight ratio active slgA/active IgG for these heat treated milks.

Table 2 - pasteurized milk data Example 3

The heat-treated milk samples of Example 2 were used to prepare a whey protein concentrate with a protein content of 70 wt%, as follows.

First of all, cheese was produced from said milk samples and the resulting whey was collected. The whey was subsequently concentrated to a protein content of 35 wt% using a 10 kD UF spiral wound membrane.

A second filtration was performed using a ceramic membrane with a pore size ranging from 0.5 to 2.0 pm in order to reduce the microbial count. The resulting permeate was subjected to a second ultrafiltration in order to increase the protein content to 70 wt%. The resulting whey protein concentrate was finally pasteurized at 75°C, 20 seconds.

The total protein content was determined using the Kjeldahl method (conversion factor 6.38). The active slgA and active IgG contents were determined by the same method as in Examples 1 and 2.

Table 3 - WPC data

Example 4

Milk from Example 2 was microfiltered and skimmed. The microfiltered skimmed milk was standardized on a whey protein/casein weight ratio of 1.1. using Hiprotal® Milkserum 60 Liquid (FrieslandCampina, The Netherlands). To this were added a premix of minerals, a premix of vitamins, and lactose. The resulting blend was heat treated for 30 seconds at 75°C, and evaporated in a Mechanical Vapor Recompression evaporator at 60°C. Afterwards, a vegetable fat blend was added and the product was homogenized and spray-dried. The resulting base powder was dry blended with the WPC of Example 3 in order to obtain a whey protein/total protein weight ratio of 0.64 and a whey protein/casein weight ratio of 1 .76 . The final product (IFT) contained 10.2 g protein and 26 g fat per 100 g powder. The active slgA and IgG levels and the ratio active slgA/active IgG in the final IFT formula product are summarized in Table 4.

Table 4 - IFT data

Claims

1. Use of mature milk from ruminants with a parity of at least 3 in a process for producing dairy products with a high active immunoglobulin content and a high weight ratio active slgA / active IgG; preferably a use of mature milk from ruminants with a parity of at least 3 in a process for producing dairy products with an active immunoglobulin content of at least 430 pg/mL and a weight ratio active slgA / active IgG of at least 0.14, said process involving the steps of collecting mature milk from ruminants with a parity of at least 3, and optionally subjecting said milk to a pasteurization treatment; wherein active immunoglobulins are immunoglobulins that are in native state; and the active immunoglobulin content and active slgA / active IgG weight ratio are determined by use of the bovine ELISA quantitation set as described by R. L. Valk-Weeber, T. Eshuis-de Ruiter, L. Dijkhuizen, S.S. van Leeuwen (International Dairy Journal, Volume 110, November 2020, 104814), preferably the active immunoglobulin content is at least 446 pg/mL and the weight ratio active slgA / active IgG is at least 0.15.

2. Use according to claim 1 wherein the ruminant is selected from the group consisting of goats, sheep, and cattle, preferably selected from goats and cows, more preferably cows.

3. Heat treated mature ruminant milk comprising at least 0.50 g active immunoglobulins per 100 gram protein and a weight ratio active slgA / active IgG of at least 0.13; wherein the heat treatment is a pasteurisation process; the active immunoglobulins are immunoglobulins that are in native state; and the active immunoglobulin content and active slgA / active IgG weight ratio are determined by use of the bovine ELISA quantitation set as described by R. L. Valk-Weeber, T. Eshuis-de Ruiter, L. Dijkhuizen, S.S. van Leeuwen (International Dairy Journal, Volume 110, November 2020, 104814).

4. Heat treated mature ruminant milk according to claim 3 wherein the milk is bovine milk.

5. Process for producing the heat treated ruminant milk product of claim 3 or 4, by pasteurizing mature milk obtained from ruminants with a parity of at least 3.

6. Whey protein concentrate or serum protein concentrate comprising at least 9 g active immunoglobulins per 100 gram protein and a weight ratio active slgA / active IgG of at least 0.10; wherein active immunoglobulins are immunoglobulins that are in native state; and the active immunoglobulin content and active slgA / active IgG weight ratio are determined by use of the bovine ELISA quantitation set as described by R. L. Valk-Weeber, T. Eshuis-de Ruiter, L. Dijkhuizen, S.S. van Leeuwen (International Dairy Journal, Volume 110, November 2020, 104814).

7. Process for producing the whey protein concentrate or serum protein concentrate of claim 6, comprising the steps of separating mature milk from ruminants with a parity of at least 3 in a whey protein-rich fraction and a casein- rich fraction, and concentrating and drying the whey protein rich fraction, wherein the process contains at least one step of reducing the count of micro organisms, preferably a pasteurization step.

8. Process according to claim 7 wherein milk is bovine milk.

9. Nutritional composition comprising the heat-treated milk according to claim 3 or 4 and/or the whey protein concentrate and/or serum protein concentrate according to claim 6, the composition comprising at least 0.50 g active immunoglobulins per 100 gram protein and a weight ratio active slgA / active IgG of at least 0.10; the active immunoglobulins are immunoglobulins that are in native state; and the active immunoglobulin content and active slgA / active IgG weight ratio are determined by use of the bovine ELISA quantitation set as described by R. L. Valk-Weeber, T. Eshuis-de Ruiter, L. Dijkhuizen, S.S. van Leeuwen (International Dairy Journal, Volume 110, November 2020, 104814).

10. Nutritional composition according to claim 9 wherein the nutritional composition is an infant formula, follow-up formula or growing-up milk.

11. Use of the heat-treated milk according to claim 3 or 4 and/or the whey protein concentrate and/or serum protein concentrate according to claim 6 in a nutritional composition.

12. Use according to claim 9 wherein the nutritional composition is an infant formula, follow-up formula or growing-up milk.

13. Process for producing the nutritional composition of claim 9 or 10 by combining milk, at least a lipid source, a carbohydrate source, vitamins and minerals, wherein the milk is a heat-treated milk according to claim 3 or 4.

14. Process for producing the nutritional composition of claim 9 or 10 by combining heat-treated milk, at least a lipid source, a carbohydrate source, vitamins and minerals, and a whey protein concentrate or serum protein concentrate, wherein the whey protein concentrate or serum protein concentrate is a whey protein concentrate or serum protein concentrate according to claim 6.

15. Process according to claim 12 wherein the milk is a heat-treated milk according to claim 3 or 4.