Yekaterina Koloskova

Vaccination is the use of antigenic material (a vaccine) to

stimulate an individual's immune system to develop adaptive
immunity to a pathogen.
-«training of immunity».
Vaccine prophylaxis - the most reliable way of preventing
serious diseases
 Main dates in vaccination history
1769 • the first immunization against smallpox, Dr. Jenner
1885 • the first immunization against rabies, Louis Pasteur
1891 • The first successful serotherapy of diphtheria, Emil von Behring
1913 • the first preventive vaccine against diphtheria, Emil von Behring
1921 • the first vaccination against tuberculosis
1936 • The first vaccination against tetanus
1936 • the first influenza vaccination
1939 • The first vaccination against tick-borne encephalitis
1953 • The first test of polio inactivated vaccine
1956 • Polio live vaccine
1980 • WHO statement about the complete elimination of human smallpox
1984 • the first publicly available vaccine for the prevention of chickenpox
1986 • The first genetic engineering hepatitis B vaccine
1987 • The first conjugate vaccine against Hib
1992 • The first vaccine for the prevention of hepatitis A
1994 • The first combination acellular pertussis vaccine (DTaP)
1996 • The first vaccine for the prevention of hepatitis A and B
1998 • The first combination acellular pertussis vaccine (DTaP Polio +)
• Development of a new conjugate vaccine against meningococcal C
1999 infection
2000 • the first pneumococcal conjugate vaccine
2006 • Human papillomavirus
2020 • COVID-19 - vaccines
 Subunit (purified protein,
Live attenuated Killed whole organism Toxoid recombinant protein, Virus-like particle
polysaccharide, peptide)

Acellular pertussis (aP),

Tuberculosis (BCG), Oral
polio vaccine OPV), Measles,
Rotavirus , Yellow fever
Haemophilus infuenzae type
b (Hib),
Pneumococcal (PCV-7, PCV-
Whole-cell pertussis (wP)
Tetanus toxoid (TT), 10, PCV-13)
Inactivated polio virus (IPV)
Diphteria toxoid Hepatitis B (HepB)

Outer membrane Protein-polysaccharide

Viral vectored Nucleic acid vaccine Bacterial vectored
vesicle conjugate

Viral vector
Pathogen gene
Pathogen Ag Polysaccharide Pathogen gene RNA
Viral vector Bacterial vector
Gram- bacteria Carrier protein gene Lipid coat
DNA
outer
membrane

Antigen-presenting cell

Patbhogen Ag

MHC
 Selection of attenuated (weakened) mutants from patients
(vaccine strain of mumps virus Daryl Lynn) or from the
external environment;
 Selection of clones vaccine (strain STI anthrax);
 Long-term passaging in the body of experimental animals
and in chicken embryos (17D strain of yellow fever virus);
 Hybridization with strains, harmless to humans (live
influenza vaccines).
Requirements:
 Should be made from attenuated (weakened) strains;
 Be avirulence - lack the ability to cause disease;
 Retain the ability to replicate in the vaccinated;
The advantage of live vaccines - the formation of stable immune system.
 Inactivated whole-cell vaccines may not
always induce an immune response and the
response may not be long lived.
 Several doses of inactivated whole-cell
vaccines may be required to evoke a
sufficient immune response
 Inactivated whole-cell vaccines have no risk
of inducing the disease they are given against
as they do not contain live components.
 They are considered more stable than LAV
vaccines.
  Subunit vaccines, like inactivated whole-cell vaccines do not contain live components of the pathogen.
They differ from inactivated whole-cell vaccines, by containing only the antigenic parts of the pathogen.
These parts are necessary to elicit a protective immune response.
 This precision comes at a cost, as antigenic properties of the various potential subunits of a pathogen must
be examined in detail to determine which particular combinations will produce an effective immune
response within the correct pathway.
 Often a response can be elicited, but there is no guarantee that immunological memory will be formed in
the correct manner.
polysaccharide

 Are thimic-independent antigens;

vaccines

 Conjugates is used for generation T-cell memory immune:

 to a carrier protein (diphtheria or tetanus toxoid) in an amount not to stimulate the production of
corresponding antibodies;
 With the protein of the microorganism (for example - outer shell pneumococcus).
 Toxoid vaccines are based on the toxin produced by certain bacteria (e.g. tetanus or diphtheria).
 The toxin invades the bloodstream and is largely responsible for the symptoms of the disease.
 The protein-based toxin is rendered harmless (toxoid) and used as the antigen in the vaccine to
elicit immunity. To increase the immune response, the toxoid is adsorbed to aluminium or calcium
salts, which serve as adjuvants
 Contain the immunizing
antigen conjugated to the
immunomodulator:
 Immunomodulators:
polyoxidonium (under
development-immunofan,
Gepon);
 to reduce the dose of
antigen;
 to increase the ability of the
immune system to produce
antibodies.
Preclinical 1st phase 2nd phase 3rd phase
• Animals • Adult volunteers • Target group • Effectiveness evaluation
• Dose selection

Dozens of people Hundreds of people Thousands of people

Assessment of safety, Target age group Target age group
tolerability and Assessment of safety, Evaluation of effectiveness
immunogenicity tolerability and in the "field conditions"
immunogenicity

4th phase
 Conducted after state registration
https://ria.ru/20130701/946812480.html
 Large number of participants
 Identification of rare and very rare adverse reactions
 Allow to evaluate the population effect of the drug, its
epidemiological effectiveness
 Harmlessness Reactogenicity Immunogenicity

• testing on laboratory • study of adverse local • expressed in

animals of toxicity, and general reactions immunizing units - in
pyrogenicity, sterility, to the introduction of antigen doses
allergenicity, animals and humans protecting 50% of
teratogenicity, immunized animals
mutagenicity infected with a certain
number of infectious
doses of a pathogenic
microbe or toxin
 Ballast
impurities

Excipients

immunizing
antigen
 Chemical substances that stimulate an
immune response, enhancing vaccine
efficacy

The main effect

Contact of the antigen with the
cells of the immune system to Reducing the toxicity of some Ensure the solubility of certain
influence the type and quality antigens vaccine components
of the immune response
 Adjuvants
Stabilizers (ensure
Adjuvants (reduce
the stability of the Preservatives
the antigenic load,
antigenic properties) (supporting the
reduce
It does not affect the sterility of vaccine)
reactogenicity)
reactogenicity

Aluminum hydroxide,
Saccharose, lactose, Merthiolate
aluminum phosphate,
human albumin, (thiomersal), 2-
polioxdonyi, Cholera
sodium glutamate fenoxiethanol
toxin, and others
 Type of
Examples Mechanisms
Adjuvants
Mineral aluminum oxide hydrate Stimulate mainly humoral
aluminum phosphate immunity, acting on the auxiliary
and Th2-cells
Vegetative Saponin (veterenary) Increases the action of the T-
dependent and T-independent
antigens
Microbial Microbial cells and their fractions M. Versatile mechanisms of influence
adjuvants tuberculoses, B. pertussis derivatives on the humoral and cellular
of muramyl dipeptide - wall immunity
components of mycobacteria low
molecular weight yeast RNA
Cytokines Interleukin-2 Stimulates cellular immunity
Interferon-Gamma

Synthetic Polioksidoniy Stimulation of T-independent

adjuvants immune response, bypassing
genetic control
Age Vaccines
BCG HBV OPV/IPV aDTP Hib PCV13 MMR DT
1-4 days
2 months
3 months
4 months
12-15
months
18 months
6 years
16 years
Every 10
years
Passive immunity is protection by antibody or antitoxin produced by one animal or
human and transferred to another. Passive immunity provides immediate protection
against infection, but that protection is temporary. The antibodies will degrade
during a period of weeks to months, and the recipient will no longer be protected.
  preparations from the blood of animals and humans containing antibodies
against pathogens of infectious diseases ortheir metabolic products.
 The introduction of serum into the human body creates passive immunity
 Immunity is created quickly, but holds for a short time, because the introduced
protein is rapidly destroyed.
 Sera have an immediate effect by neutralizing toxins, destroying the bacteria
themselves. Therefore, they are used mainly for treatment and less often for the
purpose of prevention.
 Introduced more frequently intramuscularly.
 Immunization of animals
Heterologous
 High concentration of antibodies
(derived from the  Unlimited selection of producers
blood of animals)  High immunogenicity (foreignness) -special care when using
Serum
preparations
Homologous  Not immunogenic
(derived from  From donor or placental blood
human blood)  Ab concentration is not high. This may contain other Ab.

Antibacterial
Antitoxic serum
serum
Immunize horses, donkeys. Immunize horses. Effective.
Ineffective. Anti-diphtheria
 Anthrax Anti-tetanus
 Anti-plague Anti-gangrene
Injected by Bezredko
 Anti-leptospirosis Anti-botulism
 Influenza virus Anti-staphylococcal
- Treatment of infectious diseases
(inactivation of pathogens,
toxins)
- prevention & prophylaxis of
infectious diseases
- Identification of pathogen
1)Animals immunization => plasma =>
serum
2) Animal cell cultures cultivation
Purification of serum from ballast proteins by fractionation methods using alcohol-
water mixtures at a temperature of 0°C, ultracentrifugation, electrophoresis,
enzymatic hydrolysis
Purified and concentrated preparations of the gamma globulin fraction of whey proteins
containing high titers of antibodies are called immunoglobulins, and in practice -
gamma globulins.
These are highly purified concentrated gamma globulins of humans
and animals.
2 types:
1. Normal (obtained from donor, abortive, placental blood)
 Anti-measles
 Poliomyelitis
 Against whooping cough
2. Directional action (obtained from the immune sera of human
donors and animals)
 Against rabies
 Against smallpox
 Against tetanus
These are diagnostic serums and diagnosticums
intended for the formulation of diagnostic reactions.
Diagnosticums are a suspension of dead bacteria of a
certain type. Their variety is erythrocyte diagnosticum
(bacterial Ag adsorbed on erythrocytes).
Diagnostic sera - Аb, obtained by immunization of
animals (rabbits, rams) with the corresponding AG.
Allergens - drugs for the production of skin tests and
identify allergic conditions. Show the infection of the
body.
Hybridoma technology method:

cancer cells that

can replicate  Expensive to produce
endlessly
 Single Ab species
 Will only bind to specific
hybridomas site
 May recognize a
that produce particular protein form
antibodies
continuously
mammalian cells
(particularly with
spleen cells)
capable of
producing specific
antibodies

к.б.н., доц. Сальникова Н.А. Лекция 8. Иммунобиотехнология//Кафедра фармакогнозии, фармацевтической

 Oncopathology diagnostics and therapy (Herceptin and MabThera)
 to neutralize lymphocytes responsible for transplant rejection and
autoantibodies formed in autoimmune diseases (diabetes, multiple sclerosis,
rheumatic diseases)
 for differential diagnosis of infectious and non-infectious diseases,
 to standardize the determination of blood groups.
 diagnostics, such as identifying a particular hormone,viral or bacterial
antigens.
 release of biologically active substances (proteins, hormones,toxins) from
complex mixtures
 use as labels to accurately identify specialized cells such as neurons
 use as a standard reagent for detecting certain molecules on the cell
membrane, and for separating the population of cells carrying different
antigens on the surface.
 development of highly specific vaccines, especially against certain viral strains
and parasites.
 1. Immunochemical analyzes of biological
fluids, cells of microorganisms, viruses,
etc.
2. Immunohistochemical methods
3. Immunoscintigraphy of tumors
1. Study of the etiology and 4. Typing of blood groups and tissues
pathogenesis of various diseases Diagnostics
2. Study of systemic and intersystem
mechanisms of regulation
3. Creation of new medical biological
products

Fields of
monoclonal
Research therapy
Ab
application

1. Impact on certain cell populations

2. Influence on immune regulatory
mechanisms using antibodies to
lymphokines
technology 3. Immunoregulation with anti-idiotypic
antibodies
4. Targeted drug transport using
monoclonal antibodies.
5. Elimination of toxins, immunoglobulins
1. Identification of molecules from the IgE class
2. Purification of cells bearing a specific antigen
Doctor, this vaccine is
for what?