The problem of post-vaccination immunity in children with chronic herpesvirus infections

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The problem of post-vaccination immunity in children with chronic herpesvirus infections

Melnyk Ganna

Postgraduate

National Academy of Medical Sciences of Ukraine Mechnikov Institute of Microbiology and Immunology, Ukraine

Academic supervisor: Volianskyi Andriy

MD, PhD, D.Hab

National Academy of Medical Sciences of Ukraine Mechnikov Institute of Microbiology and Immunology, Ukraine

Smilianska Maiia MD, PhD, leader researcher National Academy of Medical Sciences of Ukraine Mechnikov Institute of Microbiology and Immunology, Ukraine

The category of children with health disorders occupies a special place in the problem of vaccination of the population and the creation of long-term strained immunity to current infections. These are children with allergic, oncological diseases, central nervous system pathology, autoimmune disorders, systemic diseases of connective and supporting tissue, and chronic infectious diseases. Among these children, a special place is occupied by children who are sick often and for a long time. In these patients, the individual scheduled vaccination schedule is often disrupted due to repeated respiratory infections. Often, paediatricians give such children unreasonably long withdrawal from vaccinations due to fear of developing post-vaccination complications in them. In addition, in many cases, vaccination is not carried out, mistakenly believing that vaccination will still be ineffective, since the child's body, which is often sick, is not capable of an adequate immune response.

Until now, the course of the immune post-vaccination process, the patterns and mechanisms of the formation of stable long-term specific immunity when using various types of vaccines (bacterial, viral, molecular, corpuscular, mono- or complex drugs, etc.), the dynamics of immunological indicators during the formation of vaccine immunity in various contingents of patients.

For children with chronic pathology, most of whom remain socially active, the creation of a full-fledged individual immunity against managed infections is of particular importance. Until now, there is not only a single approach to immunization of persons with chronic pathology, but also a clear idea of the patterns and mechanisms of the formation of vaccine immunity in this category of population, which dictates the need for a step-by-step detailed study of changes in its immune status after vaccination, as well as the creation manuals and specific practical recommendations regarding modern tactics and standards of its vaccine prevention.

Morbidity and mortality from infections and non-infectious chronic somatic diseases require constant improvement of the vaccine prophylaxis. This is dictated by the steady increase in the number of sick people among the vaccinated, the increase in the frequency of childhood infections in people older than 18 years, the increase in the number of complications after the transferred diseases, the rapid fading of vaccine immunity with age, high mortality and the development of complications that lead to disability, in particular, with influenza and pneumococcal pneumonia, the problem of creating strained immunity in the elderly. The effective fight against infections requires that more than 95% of the population is protected against them.

Weak immunity and lack of protection against infectious diseases create a niche for the circulation of pathogens and are the source of the development of epidemics and pandemics. A comprehensive study of the post-vaccination process, which covers all the regulatory systems of the body, as well as the nature of immune rearrangements in it, depending on the state of the body as a whole, is considered important in the way to solving the task set at the time.

It is widely known that the immune response to vaccine administration is not monospecific. This is a multifactorial reaction, since any, even homogeneous preparations contain a number of various peptide determinants, which consist of several amino acid residues. Antibodies of a certain specificity are synthesized for each of these peptides, and the immune response to the entire vaccine is the sum of the responses to all its peptide fragments. The response to the associated vaccine is much more complex, and after the introduction of such a drug into the body, an even greater number of antigenic determinants are formed. In addition to the humoral immune response, vaccine antigens elicit a cell-type response that further complicates the immune response. For a long time, it was believed that during the implementation of the immune response to the introduction of the vaccine, a certain competition may arise between its individual antigens for interaction with the cells of the immune system. It was established that the immune system consists of a huge number of clones of lymphocytes, ready to recognize any, even artificially created, antigen. Theoretically, there is a specific lymphocyte clone for each antigen. From a practical point of view, antigen competition in vaccines is possible and likely to matter if the preparation contains so-called "strong" and "weak" antigens or if the dose of one significantly exceeds the amount of the other. However, the correct quantitative and qualitative selection of vaccine components in most cases allows for solving the problems of competition and optimizing the post-vaccination immune response.

The creation of persistent immunity to infections depends not only on the quality of the vaccines used but, to a greater extent, on the immunoreactivity of patients. The body's resistance to infectious agents, as is known, depends on the reactions of innate and acquired (adaptive) immunity. The innate immune system protects the body with the help of humoral and cellular constitutive factors - pro- inflammatory cytokines (TNFa, IFNy, IL-6, IL-1), proteins of the "acute phase of inflammation" (pentraxins), complement, natural IgM antibodies, endogenous antibiotics (defensins, cathelicidins), monocytes-macrophages, neutrophils, PC cells, T-lymphocytes, dendritic cells, etc.

The immune defence against most infectious diseases is based on humoral reactions, which play the main role, and the intensity of post-vaccination immunity is inferred from the titer of specific antibodies produced in the body and their duration of stay in the bloodstream. At the same time, cell-type reactions are not taken into account, which plays a significant role in the protection of the body during viral infections. It should be noted that the effectiveness of post-vaccination immunity is determined by a set of humoral and cellular reactions, their interrelation and control mechanisms. Unfortunately, there are currently no fast, convenient and informative methods for assessing cellular immunity, especially for mass research.

WHO warns the world community about the danger of a hidden pandemic of herpes infection. According to the WHO, almost 50% of patients infected with herpes viruses have relapses of the disease every year due to the lack of stable immunity. It is they who make up the contingent of patients with chronic recurrent herpesvirus infection. Herpesviruses are the second most common cause of death after influenza - more than 15% of cases [1]. The persistence of herpesvirus infection leads to the occurrence of immune deficiency, which is the pathogenetic background that forms the contingent of children who often get sick. Thus, it is clear that people with chronic herpesvirus infection (CHVI), precisely as a result of their inherent immune deficiency, are prone to frequent infections and constitute a group of increased risk, which most need timely active immunoprophylaxis of infectious diseases.

The steady increase in the frequency of herpes diseases in adults and children, the increase in the frequency of severe and generalized forms, the variety of clinical manifestations of herpes virus infection (HVI), lifelong persistence in the body, the ubiquity and wide distribution of herpes viruses (HV), determine the need for a comprehensive study of this pathology [1]. GVs are capable of replicating in the conditions of a fully functioning immune system, as well as causing various manifest forms of the disease when the body is weakened. HBV infects a person at an early age and can affect almost all organs and systems of the host's body, causing most often latent (with a minimal harmful effect), acute and chronic (in the event of immunodeficiency) forms of infection [2]. At this time, the mechanisms of the formation of the immune response in chronic herpesvirus infection have not been thoroughly studied. However, it was established that one of them is the development of immunosuppression, which is due to the insufficiency of various parts of the immune system and its inability to prevent the reactivation of the virus and suppress its replication. GVs can persist in the target cells of the body without symptoms in the normal state of the immune system, but in people with immunosuppression, they cause severe diseases, with a possibly fatal outcome [1]. The clinical picture of chronic GVI in adults is characterized by the presence of long-term symptoms of intoxication, lymphadenitis, tonsillitis, adenoiditis, hepato- and splenomegaly, uveitis, central nervous system pathology, etc [3]. From the point of view of the immune status, chronic herpes infection in adults has the following trends: a decrease in the absolute number of C D 4+ cells and natural killers, an increase in the absolute number of C D 8+ cells, a decrease in the concentration of antibodies with an increase in the content of virus-specific IgM and IgG, a decrease in the level of IFN - y. As for children, there are only separate works devoted to the description of small groups of patients with chronic GVI. At the same time, the issue of clinical manifestations of chronic herpesvirus infection in children is debatable.

HBs infecting immunocompetent cells (lymphocytes, macrophages, dendritic cells), reduce their functional activity [4]. GV latency has special mechanisms (different from the mechanisms of normal replication), which are not controlled either by immunity or by modern chemotherapy and remain insufficiently studied to date. The latent genome retains the ability to replicate and can cause GVI relapse. Mechanisms of reactivation of the virus from the latent state are not fully understood and differ in different HCVs.

In the last decade, data appeared that even in an inactive latent state, GVI modulates the immune system. Accordingly, the modulation of HCV's immune response can influence vaccination results [5]. The results of research on the impact of latent GVI on vaccination, conducted on different age groups, are quite contradictory.

Viremia was found in children who are often sick. The presence of viremia suppresses the immune system and causes an imbalance in the immune response, which can also affect the results of vaccination. Therefore, the study of the humoral and cellular immune response during the vaccination of children with herpesvirus viremia is an urgent need. Thus, the currently available results of vaccination studies against the background of GVI pose the question of the effect of viral infection on humoral and cellular immunity. Secondly, to identify the impact of GVI on the results of vaccination, it is necessary to study the relationship with both latent and activated forms of GVI in children. Third, the reactivation of HHV4 and HHV-6 can cause chronic fatigue syndrome (CFS). The results of routine vaccination in such children have not been studied. It is also necessary to consider that the results of vaccination may depend on the duration of CFS disease.

People are usually infected with several viruses. On average, each person can be affected by more than 10 chronic systemic viral infections. The number of viruses containing double-stranded DNA (herpesviruses, papillomaviruses, adenoviruses, polyomaviruses parvoviruses, anelloviruses, and circoviruses ) on average reaches 5. It is assumed that one of the reasons for the lack of protective effect of the vaccine is the so-called faith, that is, the composition of all viruses in the body. Verom, which controls the immunophenotype, can modulate the response to vaccination.

Therefore, to predict the results of vaccination, it is necessary to identify and study the composition of GVI with which the infected organism and the stage of GVI.

A comprehensive study of the post-vaccination process, which covers all the regulatory systems of the body, as well as the nature of immune rearrangements in it, depending on the state of the body as a whole, is considered important in the way to solving the task set at the time.

At present, there are no methodical approaches to the assessment of postvaccination immunity disorders in children with chronic herpesvirus infections, and no algorithm has been developed for the formation of an evidence base for the role of herpesviruses in the development of these disorders, the presence of which will allow the development of a set of additional measures aimed at increasing the effectiveness of vaccine prevention of controlled infections in children. vaccination immunity herpesvirus infections

Solving this problem requires an understanding of the patterns of development of the immune response to various types of vaccine antigens, the role of individual cells and links of the immune process in the formation of long-term memory, mechanisms of control and regulation of the body's post-vaccination reaction.

References:

[1] Baggaley RF, Griffin JT, Chapman R, Hollingsworth TD, Nagot N, Delany S, Mayaud P, de Wolf F, Fraser C, Ghani AC, Weiss HA. (2009) Estimating the public health impact of the effect of herpes simplex virus suppressive therapy on plasma HIV-1 viral load. AIDS. 23(8):1005-13.

[2] Kassebaum N, Kyu HH, Zoeckler L, Olsen HE (2017) Global Burden of Disease Child and Adolescent Health Collaboration; Child and Adolescent Health From 1990 to 2015:

Findings From the Global Burden of Diseases, Injuries, and Risk Factors Pediatr.;171(6):573-592.

[3] Engel EA, Song R, Koyuncu OO, Enquist LW. (2015) Investigating the biology of alpha herpesviruses with MS-based proteomics. Proteomics. 15(12):1943-56.

[4] Frappier L. (2021) Epstein-Barr virus: Current questions and challenges. Tumour Virus Res. 12:200218.

[5] Naqvi AR. (2020) Immunomodulatory roles of human herpesvirus-encoded microRNA in host-virus interaction. Rev Med Virol. 30(1):e2081.

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