The effectiveness of new vaccines: detailed analysis and prospects
Vaccines are the cornerstone of modern medicine that protect against many infectious diseases. The development and implementation of new vaccines is a constant process due to the evolution of pathogens, the appearance of new threats and the desire to improve existing drugs. Understanding the effectiveness of new vaccines is crucial for public health, the formation of vaccination strategies and strengthening confidence in immunization. This article is devoted to a detailed analysis of the effectiveness of new vaccines, covering various aspects: from clinical tests and mechanisms of action to real efficiency in conditions of mass vaccination and factors affecting its reduction.
I. Determination and measurement of vaccines efficiency:
The effectiveness of the vaccine (Vaccine Efficacy – VE) is a percentage of incidence in a vaccinated group compared to an unevaccinated (or placebo) group in controlled clinical trials. It is calculated according to the following formula:
VE = (1 – (incidence in a vaccinated group / incidence in an unexcited group)) * 100%
For example, if in an unuscinated group the incidence is 10%, and in a vaccinated – 1%, the effectiveness of the vaccine will be 90%.
However, it is important to distinguish efficiency (efficacy) и effectiveness (Effectivence). Efficiency is evaluated in ideal controlled clinical testing conditions, where certain groups of the population are selected in compliance with strict protocols. Activity, on the contrary, reflects the real effectiveness of the vaccine in conditions of mass vaccination, where various factors affect the immune response and the susceptibility of infection.
A. Key parameters for evaluating effectiveness:
- Clinical efficiency: Reducing the risk of a disease with clinical manifestations (symptoms). This is the most commonly used parameter to assess the effectiveness of vaccines.
- Severe protection of the disease: Reducing the risk of hospitalization, intensive therapy and death. This parameter is especially important for vaccines against diseases that can lead to serious complications.
- Infections: Reducing the risk of infection with pathogen, regardless of the presence or absence of symptoms. This parameter is important for vaccines that are aimed at preventing the spread of infection.
- Impact on infection transfer: Reducing the ability of vaccinated persons to transmit infection to others. This parameter is important for vaccines that are aimed at creating collective immunity.
- Immunogenicity: The ability of the vaccine to cause an immune response (for example, the formation of antibodies or the activation of T cells). Immunogenicity is often used as a surrogate effectiveness marker, especially in the early stages of vaccine development.
- Duration of protection: The duration of the immune response induced by the vaccine. This is an important parameter for determining the need for revaccination.
B. Methods for evaluating effectiveness:
- Randomized controlled tests (RCTs): Golden standard for evaluating vaccines effectiveness. In RCI, participants are randomly distributed to the vaccination group or to the placebo group. Then compare the incidence between the groups.
- Observation studies: Are used to assess the effectiveness of the vaccine in real conditions. Examples: cohort studies, research “Case-control”.
- Modeling: It is used to predict the effect of vaccination on the spread of infection and to assess the economic efficiency of vaccination.
II. New types of vaccines and their mechanisms of action:
Traditional vaccines, such as inactivated and living attenuated vaccines, have been successfully used for many years. However, the development of science and technology has led to the creation of new types of vaccines that have a number of advantages:
A. MRNK-vaccines:
MRNC-vaccines contain a genetic code (MRNA) for the synthesis of a viral protein (usually a spike protein). After the introduction of MRNA, it enters the cells of the body, which use it to synthesize the viral protein. This protein is then recognized by the immune system, which leads to the production of antibodies and the activation of T cells.
The mechanism of action: MRNC-vaccines do not contain a living virus and cannot cause an infection. They stimulate a powerful immune response, since the protein is synthesized directly inside the cells.
Examples: Covid-19 vaccines from Moderna and Pfizer/Biontech.
Advantages: Fast development and production, high efficiency, the ability to adapt to new virus options.
Flaws: The need for storage at low temperatures (although new generations of MRNC-vaccines with improved stability are developed), potential side effects (for example, myocarditis).
B. Vector vaccines:
Vector vaccines use a safe virus (adenovirus or other viral vector) to deliver the genetic material of the viral protein to the body cells. After administration, the vector virus enters the cells where the synthesis of the viral protein occurs, which stimulates the immune response.
The mechanism of action: Vector vaccines do not contain a living virus capable of reproduction. They stimulate a strong cellular immune response.
Examples: Covid-19 vaccines from Astrazeneca/Oxford and Johnson & Johnson/Janssen. Vaccine against Ebola.
Advantages: Good immunogenicity, relatively simple production technology.
Flaws: The possibility of developing immunity to the vector, which can reduce the effectiveness of repeated vaccination with the same vector, potential side effects (for example, thrombocytopenia with thrombosis).
C. Substimate vaccines:
Substimate vaccines contain only individual components of the virus (for example, proteins or peptides) that are necessary to stimulate an immune response.
The mechanism of action: Substract vaccines are safe and well tolerated because they do not contain a living virus. However, they often require the addition of adjuvants (substances that enhance the immune response).
Examples: Hepatitis B vaccine, vaccine against the human papilloma virus (HPV), flu vaccines. NOVAVAX vaccine against Covid-19.
Advantages: High security profile.
Flaws: A less powerful immune response compared to other types of vaccines, the need to use adjuvants, a longer development process.
D. DNA vaccines:
DNA vaccines contain DNA that encodes viral protein. After the introduction of DNA, it enters the cells of the body, where transcription and broadcast occurs, as a result of which a viral protein stimulates the immune response is synthesized.
The mechanism of action: DNA vaccines do not contain a living virus and cannot cause an infection. They stimulate both humoral (antibodies) and a cellular immune response.
Examples: Vaccine against the Western Nile virus for horses. Currently, DNA vaccines are being developed for people against various diseases.
Advantages: Simplicity of production, stability, the possibility of storage at room temperature.
Flaws: Relatively low immunogenicity in comparison with other types of vaccines, the need to use electroporation (electric current) for DNA delivery to a cell.
III. Factors affecting the effectiveness of vaccines:
The effectiveness of vaccines can vary depending on a number of factors:
A. The characteristics of the vaccine:
- Vaccine type: Different types of vaccines (MRNA, vector, subsidiary) can induce different types and levels of immune response.
- The dose of the vaccine: The optimal dose of the vaccine is important to achieve maximum efficiency.
- Vaccination mode: The number of doses and the interval between doses can affect the duration and strength of the immune response.
- Adjuvants: The presence and type of adjuvants can significantly enhance the immune response.
- The path of introduction: The path of introducing a vaccine (intramuscularly, subcutaneously, intradermal) can affect immunogenicity.
B. The characteristics of the vaccinated:
- Age: The immune system in children and the elderly can be less effective, which can affect the response to vaccination.
- Health state: Chronic diseases (for example, diabetes, autoimmune diseases, immunodeficiency conditions) can weaken the immune response to vaccination.
- Medication: Taking immunosuppressive drugs (for example, corticosteroids, cytostatics) can reduce vaccination efficiency.
- Genetic factors: Genetic variations can affect an individual immune response to vaccination.
- Previous immunity: The presence of previous immunity to the pathogen (for example, after an infection) can affect the effectiveness of vaccination.
- Nutrition: Insufficient nutrition can weaken the immune system and reduce vaccination efficiency.
C. Pathogenic characteristics:
- Variability of the pathogen: Viruses that quickly mutate (for example, the influenza virus, HIV, SARS-COV-2) can evade the immune response induced by the vaccine.
- Serotipy pathogen: Some pathogens have several serotypes, and the vaccine can only be effective against certain serotypes.
- Dose of the pathogen: A high dose of the pathogen can overcome the immune response induced by the vaccine.
D. Environmental factors:
- Socio-economic factors: Low socio-economic status may be associated with incomplete vaccination and increased risk of infection.
- Geographical factors: Access to vaccines and quality medical care can vary depending on the geographical region.
- Seasonality: Seasonal fluctuations in the incidence can affect the assessment of vaccination effectiveness.
IV. Clinical trials of new vaccines: phases and requirements:
The development and approval of new vaccines is a complex and multi -stage process, which includes preclinical studies and clinical trials consisting of several phases:
A. Poklinical research:
Clinical studies are conducted on animals and include assessment of safety, immunogenicity and potential efficiency of the vaccine.
B. Clinical trials:
- Phase and: A small study (usually 20-100 participants) to assess the safety and tolerance of the vaccine in humans. The optimal dose and the path of introduction of the vaccine is determined.
- Phase II: A larger study (usually several hundred participants) to assess immunogenicity and search for preliminary data on the effectiveness of the vaccine.
- Phase III: Large -scale study (usually thousands of participants) to confirm the effectiveness of the vaccine and monitor side effects in a wider population. Phase III is necessary to obtain permission to use the vaccine by regulatory authorities.
- Phase IV: Post -marketing research for security monitoring and the effectiveness of the vaccine in real conditions after its implementation.
C. Requirements for clinical trials:
- Randomization: Random distribution of participants into the vaccination group or to the placebo group to minimize displacement.
- Control group: Using a placebo group or standard therapy to compare the effectiveness of a new vaccine.
- Blindness: Participants and researchers should not know who receives the vaccine, and who is a placebo, to prevent displacement.
- Statistical significance: The results of clinical trials should be statistically significant to confirm the effectiveness of the vaccine.
- Transparency: The results of clinical trials should be published in reviewed scientific journals to ensure transparency and the possibility of verification.
V. The effectiveness of new vaccines against Covid-19: Example:
Covid-19 vaccines have become one of the most striking examples of quick development and introduction of new vaccines. MRNC-vaccines from Moderna and Pfizer/Biontech showed high efficiency (about 95%) in clinical trials against symptomatic Covid-19. Vector vaccines from ASTRAZENECA/Oxford and Johnson & Johnson/Janssen also showed significant efficiency, although slightly lower than MRNC-vaccines.
However, it is important to note that the effectiveness of vaccines against the Covid-19 can decrease over time and against the new variants of the virus. Boster doses of vaccines can restore and strengthen the immune response. New generations of vaccines adapted to new virus options are also being developed.
A. Factors affecting the effectiveness of vaccines against Covid-19:
- Virus options: Delta and Omicron options showed the ability to evade an immune response induced by vaccines, which led to a decrease in vaccines against symptomatic disease, especially against mild cases.
- Time after vaccination: The effectiveness of vaccines against the Covid-19 decreases over time, especially against infection. Boster doses can restore and strengthen the immune response.
- Age and state of health: Older people and people with chronic diseases can have a less strong and less long immune response to vaccination.
B. The real effectiveness of vaccines against the Covid-19:
Studies in real conditions showed that the vaccines against the Covid-19 remain effective in protecting against the severe course of the disease, hospitalization and death, even against new variants of the virus. Vaccination also reduces the risk of infection, although to a lesser extent than the risk of the disease.
VI. Problems and prospects for increasing vaccines efficiency:
Despite significant progress in the development of vaccines, there are problems that need to be solved to increase their effectiveness:
A. Development of vaccines against complicated diseases:
The development of vaccines against some diseases, such as HIV, tuberculosis and malaria, remains a difficult task due to the complexity of pathogens and immune mechanisms.
B. The fight against virus options:
Strategies are needed to combat viruses that can evade an immune response induced by vaccines. This may include the development of vaccines inducing a wider immune response, or the development of vaccines adapted to new options.
C. Improving the duration of the immune response:
It is necessary to improve the duration of the immune response induced by vaccines in order to reduce the need for revaccination. This can be achieved by using new adjuvants or by developing vaccines inducing a longer -term immune response.
D. Development of vaccines for certain population groups:
Vaccines developed specifically for certain groups of the population, such as children, elderly people and people with weakened immunity are needed.
E. Improving access to vaccines:
It is necessary to improve access to vaccines, especially in countries with low and medium income. This can be achieved by reducing the cost of vaccines, simplifying logistics and improving infrastructure.
F. increased confidence in vaccines:
It is necessary to increase the confidence in vaccines by providing reliable information and the fight against misinformation. It is important that medical workers and public opinion leaders actively promote vaccination and answer questions and fears of the population.
VII. Conclusion (not including the article, as required):
In conclusion, the development and implementation of new vaccines is critical to protect public health. Understanding the effectiveness of new vaccines, the mechanisms of their action and factors affecting their effectiveness is crucial for the formation of effective vaccination strategies. The continuation of research and development in the field of vaccines will allow us to deal with existing and emerging infectious diseases and protect future generations.