The main problems with the use of antibodies to prevent and control infectious diseases are the variability of the antigen. The genotype and serotype of
H. pylori of different regions varies significantly from country to country, and even between regions within the same country [
39,
40]. Previous studies have indicated that the
H. pylori-specific antibodies bind to different clinically isolated
H. pylori stains with less than a tenfold variation in titer [
38]. Our clinical trial has shown a positive effect and safety in O blood group
H. pylori-infected subpopulations following the oral administration of polyclonal antibodies in defatted milk, in which casein has not been discarded considering that casein can elevate mucus pH. However, to date, an effective treatment of the
H. pylori infection has proven difficult, considering costs, adverse effects, and the increasing emergence of antibiotic-resistant strains [
12,
13,
15,
41,
42]. The use of anti-
H. pylori bovine antibodies in milk to control the
H. pylori infection has many advantages such as low costs, nutrients, and good compliance, without the development of antibiotic resistance in
H. pylori or other flora and the tolerance of long-term use. Many factors might influence the clinical effect, including the different pH microenvironments between patients, the antibodies titers in the milk, high gastric acidity, a high bacterial load, persistent infection, bacterial self-protecting mechanisms (such as the flagella of
H. pylori, which are covered by a flagellar sheath and therefore are thought to be shielded from antibody selection), the different blood types of patients, the genotype deference between immunized and infected bacteria, the optimal length and dose of treatment, the oral administration time, and the size of the study population. However, the degree of match between the immunization and the patient infection strains might be the crucial in influencing the effect of the clinical trial. Therefore, we have selected the locally prevalent
H. pylori stains to immunize the dairy cows.
H. pylori possesses an enormous genomic diversity and plasticity that facilitate host adaptation. Simultaneously, many studies have suggested that
H. pylori has a much higher recombination rate and mutation than most other microorganisms [
43]. Variable expression of fucosyltransferases enables
H. pylori strains to alter their host-recognizable antigens by mimicking human Lewis antigens in order to evade their host’s immune response [
9,
44]. Genetic diversification of the
H. pylori adhesin genes might allow the adaptation of adherence properties to better facilitate persistence, despite host defenses. The different genotypes of
H. pylori have their respective phenotypes with regard to cell envelope and surface structure, especially their adhesins [
45]. Different adhesins bind different antigens [
46,
47]. For example, adhesins SabB and SabA bind sialic acid, and adhesin BabB binds Lewis b antigen [
47,
48]. Frequent
H. pylori infection in crowded living conditions and the clustering of the cases occurring within family units indicate that different regions have different locally prevalent strains. The local prevalent
H. pylori strains must therefore be selected to immunize the dairy cows. However, the overall efficacy of the 33.3% (10/30) clearance rate in our study is low and is not suitable clinically for the treatment of
H. pylori infection. This might be because the selected immunization strain was not the actual locally prevalent strain in our study because we screened a single
vacA gene locus. More gene loci such as the genes of the flagellum and adhesins need to be screened.
Breast-feeding during the first months after birth decreases human infant morbidity and mortality from diarrheal and systemic infection because the colostrum conveys protection to the immunologically naïve infant against a variety of microbial pathogens by immunoglobulins [
49]. Whole bovine immune-milk mimics natural protection in humans and has been used in infants for the treatment or prevention of enteric infections by bacterial, viral, and protozoal pathogens.
H. pylori expresses adhesins of BabA/B, SabA, AlpA/B, OipA, and HopZ, which confer intimate adherence to the gastric epithelium, whereby the bacteria can gain easy access to nutrients from host tissues [
10,
11,
37,
46,
48]. Antibodies against BabA/B, SabA/B, AlpA/B, OipA, HopZ, and urease can disrupt the ability of
H. pylori to colonize the gastric mucosa and limit its ability to garner essential nutrients. Our study might have been limited by the fact that we did not ascertain whether milk taken from immunized cows contained the specific antibodies mentioned above. Therefore, future research is necessary to ascertain the type of antibodies described above.