According to WHO, vaccines annually save the lives of 3 million children. With the help of new vaccines, which will be developed in the next 5-15 years, it will be possible to prevent the death of an additional 8 million children per year. The number of infections against which it is possible to create vaccines is constantly growing. For 30 years it has increased 2 times. At the stages of experimental development and clinical trials are vaccines aimed at the prevention of more than 60 types of diseases. About 6 million children die from infectious diseases, against which there are no vaccines yet.
75% of the types of infectious diseases are diseases that are not managed by means of immunoprophylaxis. In the structure of infant mortality, infectious diseases occupy the fourth place. In 2002, about 30 million cases of infectious diseases were registered in the country. Of particular importance are acute respiratory infections, acute intestinal infections, influenza, viral hepatitis.
Over the past three decades, more than 30 new nosological forms of infectious diseases have been identified (Legionnaires’ disease, Ebola and Marburg haemorrhagic fevers, viral hepatitis C, D and E, HIV infection, mycoplasmal infections, Creutzfild-Jakob prion disease, etc.).
In addition, after a certain period of well-being, there was an increase in the incidence of many “old” infectious diseases: viral (measles, mumps, rabies, dengue, yellow fever), bacterial (plague, cholera, tuberculosis, diphtheria, pertussis, typhoid fever, etc.) ), parasitic (malaria, toxoplasmosis, echinococcosis, etc.). The reason for this “return of old infections” is a whole range of factors: migration and population growth, urbanization, overcrowding, low uro-life, changes in ecology, climate, the evolution of microorganisms, tourism, labor characteristics, sanitation and other factors.
Of particular concern are infections with intracellular parasitism of the causative agent (herpes, cytomegalovirus, mycoplasmal, chlamydial infections), nosocomial infections, bacteriocarrierism and the ever increasing role of opportunistic pathogens in the development of infectious pathology. The development of means for specific prevention and treatment of these infections is associated with great difficulties.
Evidence has been obtained that microorganisms play a leading role in the etiology of many diseases previously considered non-infectious (Table 2). According to WHO, up to 84% of some forms of cancer are caused by the virus, bacteria and parasites. By preventing infections that cause tumor growth, about 15% of all new cancers can be avoided.
Infectious pathology becomes important in hepatology, rheumatology, in the development of atherosclerosis and diffuse lesions of connective tissue. It can be expected that many mental, endocrine, neurological diseases will soon enter into the category of infectious diseases. Reflection of this is a sharp increase in the range of vaccines used for specific and non-specific prevention and treatment of non-infectious diseases: allergic, autoimmune, oncological, etc.
The modern system of vaccination is a decisive factor in reducing child mortality, increasing the duration and improving the quality of life of all age groups of the population. Mankind has become vaccine-dependent. Insufficient attention to vaccination problems, reduction of vaccine coverage inevitably leads to a sharp increase in the level of infectious morbidity (outbreaks of pertussis in Japan, measles in Haiti, poliomyelitis in Chechnya, etc.).
Our ideas about contraindications to vaccination have changed. Instead of using sparing methods of immunization and numerous withdrawals from vaccination, a new slogan is put forward: chronic pathology is an indication for vaccination. Persons with this pathology constitute a risk group, which is the most susceptible to infections and which must be vaccinated in the first place. The list of contraindications to vaccination has dramatically decreased, but it is likely to be even shorter in the near future.
Individual viral vaccines not only create anti-infectious immunity, but also hinder the development of cancer diseases that occur in unvaccinated people under the influence of a viral infection. For example,
When vaccinating against hepatitis B, at the same time, primary liver cancer is prevented.
It was noted that vaccines prepared from conditionally pathogenic flora of the respiratory tract can increase resistance to influenza infection and, conversely, influenza vaccines increase resistance to nonspecific lung diseases. This is due primarily to the pronounced nonspecific protective effect that any vaccine causes. Specific prevention of poliomyelitis leads to nonspecific prevention of other enterovirus infections. It can be assumed that a nonspecific protective effect can be stronger if the compared infections have similar development mechanisms, and their pathogens have the same entrance gate and cause the same kind of immunity (humoral or cellular).
A person lives in an environment infested with various kinds of pathogens of viral, bacterial and parasitic diseases. Due to genetic variability, new species and variants of microorganisms appear in nature. Vaccines prepared for some countries may not be effective enough for other countries. This dictates the need for monitoring the genetic variability of pathogens of infectious diseases and periodically adjusting the composition of existing vaccines.
A person can not exist without a powerful defensive rapid reaction system. In addition, when this system is weakened, the balance between a person and a conditionally pathogenic flora is disturbed, which causes the development of an infectious pathology.
On earth, there are fewer epidemics, humanity has learned to fight infectious diseases through various anti-epidemic measures, including through vaccine prevention. On the other hand, the human immune system has become weaker responding to pathogens. The reasons for this are unfavorable ecological conditions, urbanization, weakening of natural immunization of people by microorganisms circulating in the environment, etc.
The widespread use of antibiotics and a large set of disinfectants reduces the circulation of pathogenic and non-pathogenic microorganisms. The successes of medical science and practice create favorable conditions for the survival of persons with a deficiency of the immune system and weaken the influence of natural selection on the life expectancy of individual people. The creation of such “greenhouse” conditions is not always useful for the human immune system. It is known that experimental animals grown under sterile conditions can not exist in a normal environment. The lymphatic system of such animals undergoes involution and is incapable of resisting even opportunistic microbes.
It is important that the human immune system is always at a certain level of activity. This provides protection against infectious, oncological and other diseases. A special role in maintaining such activity belongs to vaccines. Vaccines not only create specific protection against
specific types of infections, they have a strong nonspecific effect, stimulating numerous factors of natural resistance. From this point of view, if there were no vaccines, it would be necessary to create and use other immunobiological preparations for dosed and controlled stimulation of the human immune system. Is not the cessation of vaccination against smallpox in 1980 one of the factors that contributed to the “return of old infections” that began in the following years?
It is believed that numerous injections of vaccines can lead to antigenic overload and paralysis of the immune response. The theory and practice of vaccination shows that these fears are exaggerated. In the body there is a huge number of subpopulations of lymphocytes with different specificities, they can react even to substances that are not in nature. A healthy person with a formed immune system responds to virtually all vaccines made from those microorganisms that circulate in the environment. Naturally, there are exceptions for certain groups of people. For example, for newborns with an undeveloped immune system, for people with genetic defects, for people with immunodeficiency, organic lesions and other contraindications to vaccination.
Modern vaccination seeks the creation of ideal vaccines. The majority of existing vaccines can not be the basis for the creation of such vaccines; fundamentally new approaches are needed based on the use of knowledge about the cellular and molecular mechanisms of immune development, accurate data on the structure of antigens and their coding genes, on the use of modern biotechnology methods, and computer analysis in the selection of potential epitopes and the calculation of the intensity and nature of the immune response.
Requirements for an ideal vaccine
- The chemical composition and structure of the components of vaccines (antigens, adjuvants, carriers, etc.) should be accurately established.
- The vaccine should be administered once.
- The vaccine should be comprehensive and create immunity to many infections.
- The vaccine should provide lifelong immunity in 100% of the vaccinated.
- The vaccine should be safe and not have side effects.
- The vaccine should be administered in a convenient way for the medical staff and patients.
- The vaccine should be stable, have a long shelf life.
- The vaccine should not need to comply with the “cold chain”.
- Vaccine manufacturing technology must meet modern requirements.
- The cost of vaccines should not be high.
On average, every 1-2 years the world medical practice receives one new vaccine and several modified vaccines. A feature of modern vaccination is the development and introduction of new generation vaccines based on artificial synthesis, genetic engineering and the latest technology. The molecular structure of many pathogens of infectious diseases was deciphered, artificial viral and bacterial peptides were obtained, large-scale methods of culturing cells used for the production of viral vaccines, monoclonal antibodies, cytokines and other immunobiological preparations were developed. Started production of recombinant vaccines and vaccines with protein carriers and artificial adjuvants. Essentially new vaccines are being developed (vector vaccines, DNA vaccines, plant vaccines, etc.)
The appearance of the production of immunoprophylaxis has changed, modern biotechnology based on artificial synthesis and genetic engineering is used at enterprises, cell lines lacking the defects of primary cell cultures are increasingly being used as a substrate for the manufacture of viral vaccines, and in industrial conditions it is possible to obtain kilogram quantities of monoclonal antibodies. Many enterprises work in the conditions of computerization of the main production processes and compliance with GMP requirements.
Modern diagnostic methods (PCR, immunoblotting, IFA modifications, biosensor systems, etc.) have a high degree of sensitivity (up to a picogram amount of antigen and antibodies) and allow diagnosis of the disease early in its development. Unfortunately, the test systems for assessing cellular immunity due to their complexity have not found wide application in practice, although this type of immunity underlies the resistance to many types of infections.
Many existing vaccines, preserving their names, have been improving for decades and are now much better than their predecessors. At the same time, all vaccines without exception (domestic and foreign) are not devoid of shortcomings and need further improvement. Practice is experiencing an acute need for vaccines against mycoplasmal, chlamydial infections, HIV infection, malaria, a more effective anti-tuberculosis vaccine. The development of selective and even individual methods of vaccination is topical.
The assessment of the cost-effectiveness of vaccination has become an indispensable element of any newly developed program related to the development, testing, commercial release, monitoring and use of new vaccines. When developing a new vaccine, the fate of the drug is decided by three main factors:
- the possibility of reducing the incidence and benefits of using the vaccine;
- risk of post-vaccination complications and possible damage from vaccination;
- cost of vaccine and economic benefits.
Of course, there are no absolutely safe vaccines, however, the number of complications arising during vaccination is hundreds and thousands of times less than the number of cases of a similar pathology that is observed in infectious diseases. The cost of vaccination for any vaccine, the effectiveness of which is proven, is about 10 times less than the cost of treating an infectious disease. All costs for activities carried out under the auspices of WHO to eradicate smallpox have paid off within one month of the declaration of liquidation. The planned eradication of poliomyelitis is extremely important for all countries of the world, as huge amounts of money are being spent on vaccinating the population against this infection. Currently, more than 90% of the global health budget is spent on treatment procedures and only a tenth of the budget is spent on prevention.
Vaccination is the most massive form of medical intervention and concerns virtually every person on earth. Vaccination is carried out on healthy people, including children. In this regard, the use of vaccines, especially at the stage of clinical trials of fundamentally new vaccines, requires strict adherence to ethical norms and rules.
Unfortunately, the legal and ethical basis of vaccine prevention is far from perfect. The level of public confidence in vaccination is not high enough. Violations of legal and ethical principles give rise to discontent and negative attitudes towards vaccination activities among part of the population. One of the priorities of modern vaccinology is the improvement of knowledge in the field of medical ethics in order to achieve mutual understanding between the population and specialists involved in the development, testing and use of vaccines.