Immunity of infants
Therapeutic antibodies, "like mom's," will protect against intracellular infections
A newborn human baby is completely helpless in many ways, including immunity. Many links of the immune defense will be formed in the child over time, and in the first months of life he "borrows" it from his mother. By investigating this maternal phenomenon, scientists have found a new way to create more effective antibody-based drugs.
Almost everyone now knows what antibodies or immunoglobulins are – thanks to the coronavirus pandemic. These special immune proteins of adaptive (acquired) immunity recognize and bind antigens – particles of bacteria and viruses, toxins and other potentially dangerous agents, protecting the body from them.
Immunoglobulins are divided into five classes (IgG, IgM, IgA, IgE and IgD), while the child gets IgG class antibodies from the mother, as well as, with milk, IgA. They begin to enter his body even before birth through the placenta (the organ that unites the functional systems of the mother and embryo organisms), and later – with breast milk. It is these antibodies that restrain the onslaught of pathogens from the external environment in the first few months of the baby's life.
Not so long ago, it was believed that antibodies, in principle, are not able to penetrate into cells, and only the T-cell link of adaptive immunity fights intracellular infections. Therefore, antibodies can only be targeted at pathogens located in the extracellular environment. Accordingly, therapeutic monoclonal antibodies cannot be used to treat infections caused by intracellular pathogens.
Scientists from the USA, having studied in detail the specific maternal immunity, found that IgG mothers have special properties.
It turned out that during pregnancy, the structure of one of the elements of the variable region of this antibody changes: the monosaccharide molecule sialic acid passes from the acetylated form to the deacetylated one. In this form, it can bind to the CD22 receptor, a membrane protein of B lymphocytes, which triggers certain immune defense mechanisms. And such a fine molecular modification is enough for maternal antibodies to protect infants from intracellular infections.
The researchers conducted studies on laboratory mice, studying the biochemical parameters associated with the work of antibodies in unborn and pregnant females. It turned out that during pregnancy, the enzyme sialic acid acetylesterase is actively developed in the body of mice, which is responsible for the transformation of this molecule. In the experiment, this modification provided the offspring with protection from the causative agent of listeriosis – the intracellular bacterium Listeria monocytogenes.
The researchers supported their conclusions with the results of an experiment on genetically engineered animals in which deacetylation of sialic acid became impossible. The administration of antibodies from healthy pregnant mice to mice from such mothers restored their immune protection.
Article by Erickson et al. Pregnancy enables antibody protection against intracellular infection is published in the journal Nature.
The results of this work open up new perspectives in immunotherapy. Today, there are already quite a few drugs based on monoclonal antibodies developed for the treatment of cancer, asthma, multiple sclerosis, Alzheimer's disease, as well as some bacterial and viral infections, including COVID-19. Some of them have already been approved for use, others are undergoing clinical trials, and not all of them are successful.
According to scientists, if antibody deacetylation is reproduced "in vitro", it is possible to create more effective drugs based on monoclonal antibodies that can treat infections caused by intracellular agents. Among them, for example, are such dangerous pathogens as HIV and the respiratory syncytial virus (RSV), which is common among infants, which poses a serious and sometimes fatal danger to them.
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