Sumy State University

The Department of Infectious Diseases and Epidemiology with Course of Microbiology, Virology and Immunology

Immunotherapy and Prevention

Tatyana Ivakhnyuk 2011

Active Immunization
Stimulates the hosts immune system to produce specific antibodies or cellular immune responses or both which would protect against or eliminate a disease.

Passive Immunization
A preparation of antibodies that neutralizes a pathogen and is administered before or around the time of known or potential exposure.

Vaccines
Provide an antigenic stimulus that does not cause disease but can produce long lasting, protective immunity

Principles and Effects of Vaccination

Sterile protection
Specific
Pathogen neutralization

Non sterile protection

Specific

Quick amplification

Specific
Clearance of the pathogen after infection Intracellular pathogen with cell to cell transmission Cell mediated

Clearance of the pathogen before spreading Extra cellular pathogens or free intracellular pathogens Antibody mediated

Types of Vaccines and Their Characteristics

Vaccine technologies
Live vaccines Recombinant vaccines
Killed vaccines Plasma derived vaccines Polysaccharide conjugates Peptide vaccines Subunit vaccines DNA vaccines Combination vaccines Examples polio, yellow fever RSV influenza, pertussis Hepatitis B Hib, Pneumo Malaria HIV candidates Influenza DPT

Passive (antibodies)

e.g. HBIG, VZIG

Types of Vaccines and Their Characteristics

Attenuated whole-agent vaccines

use living but attenuated (weakened) microbes. Live vaccines more closely mimic an actual infection. Lifelong immunity, especially with viruses, is often achieved without booster immunizations, and an effectiveness rate of95% is not unusual. This long-term effectiveness probably occurs because the attenuated viruses replicate in the body, increasing the original dose and acting as a series of secondary (booster) immunizations.

Attenuated whole-agent vaccines

Ideal properties of a live vaccine

Attenuated microorganism which replicates in the host thus eliciting immune responses similar to natural infection Able to elicit lifelong protection using only one or two doses Disease causing capacity is virtually eliminated. Elicits both humoral and cellular immunity

Examples of Attenuated or live vaccines

Live attenuated vaccines oral polio, yellow fever mumps, measles, VZV tuberculosis (BCG)

Types of Vaccines and Their Characteristics

Inactivated

whole-agent

vaccines

use microbes that have been killed, usually by formalin or phenol. Inactivated virus vaccines used in humans include those against rabies (animals sometimes receive a live vaccine considered too hazardous for humans), influenza, and polio (the Salk poliovaccine). Inactivated bacterial vaccines include those for pneumococcal pneumonia and cholera. Several long-used inactivated vaccines that are being replaced for most uses by newer, more effective types are those for pertussis (whooping cough) and typhoid.

Inactivated whole-agent vaccines

Types of Vaccines and Their Characteristics

Toxoids, which

are inactivated toxins, are vaccines directed at the toxins produced by a pathogen. The tetanus and diphtheria toxoids have long been part of the standard childhood immunization series. They require a series of injections for full immunity, followed by boosters every 10 years. Many older adults have not received boosters; they are likely to have low levels of protection.

Modification of Toxin to Toxoid (example)

Extracellular Toxin Toxin tetani of Clostridiun
Tetanus Toxoid

chemical and temperature

modification
toxin moiety antigenic determinants
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Types of Vaccines and Their Characteristics

use only those antigenic fragments of a microorganism that best stimulate an immune response. Subunit vaccines that are produced by genetic modification techniques, meaning that other microbes are programmed to produce the desired antigenic fraction, are called recombinant vaccines. For example, the vaccine against the hepatitis B virus consists of a portion of the viral protein coat that is produced by a genetically modified yeast.

Subunit vaccines

Types of Vaccines and Their Characteristics

have been developed in recent years to deal with the poor immune response of children to vaccines based on capsular polysaccharides.

Conjugated vaccines

Polysaccharide vaccines
Unique type of inactivated subunit vaccine composed of long chains of sugar molecules that make up the surface capsule of certain bacteria.

Available for Pneumococcal disease, meningococcal disease and Haemophilus influenzae type b

Combination vaccines
Examples influenza trivalent OPV, inactivated IPV DPT, DPT/Hib, etc. MMR, MMRV PnC/MnC only one needle at a visit may reduce number of visits reduces costs of administration geographic tailoring loss of immunogenicity due to competition technically more difficult to produce higher production costs higher evaluation costs

Advantages:

Disadvantages:

Correlates ?
Humoral component
Tetanus Dyphteria H. influenzae Influenza Measles Varicella (herpes zoster) Dengue S. pneumoniae

Cellular components
BCG HIV Herpes type 1&2 Shingles (herpes zoster) Influenza in elderly Varicella (herpes zoster) Measles

Description of immunity
Postinfection Postvaccine Active Passive Humoral Cellular Antibacterial Antiviruses Antitoxins Antifungal Specific Nonspecific Group specific, species specific, Type-specific

BCG (bacillus Calmette-Guerin)

Content: living or attenuated, liophilic dried up culture unpathogenic strain of M. tuberculosis, was found by the French scientists Calmette and Guerin. Used for the active specific prophylaxis of tuberculosis. Plugged in the calendar of inoculations. Contra-indicated people with violation of cellular link of immunity.
What type of immunity (originally) is created in an organism after introduction?

Postvaccine Active Cellular Antibacterial General Specific

Killed brucellosis vaccine

Content: It contains the killed by
heat the cow-type and sheep-type species of the brucella. It is using for immunotherapy by chronic brucellosis. It has high sensibillization and allergic ability and it is using only for patients with normegric reaction of the organism on the intra-skin injection of the brucellin. For the patients with hyperergia and allergic reaction and for person with generalized infection the vaccination is dangerous. The intra-skin therapy is making often then intravenous. The injection of the brucellin is useful for same patients.
What type of immunity (originally) is created in an organism after introduction?

Postvaccine Active Cellular Antibacterial General Specific

Meningococcal chemical vaccine

Content: This vaccine contains cleared polysaccharide of Neisseria meningitidis group A and C. Appointment: Prophylaxis of cerebrospinal meningitis, caused meningococcus of serogroupp A and C. Vaccination is recommended in endemic regions, and also in the case of epidemic, caused meningococcus of serogorupp A or C.
What type of immunity (originally) is created in an organism after introduction?

Postvaccine Active Humoral Antibacterial General Specific

Staphylococcal toxoid
Content: this vaccine, in which contains inactivated, which help formalin (0,4%) and temperature (56C) exotoxin S.aureus. It is used for specific preventive and treatment of staphylococcal infections
What type of immunity (originally) is created in an organism after introduction?

Postvaccine Active Humoral Antitoxic General Specific

APDT
Content: - dsorbed on the hydrate of oxide of aluminium mixed vaccine, consisting of the killed microorganisms the whooping-cough bacterias and toxoids diphtherial and tetanic. Used for plannad prophylaxis.
What type of immunity (originally) is created in an organism after introduction?

Postvaccine Active Humoral Antitoxic Antibacterial General Specific

Adjuvant activity
Formation of a depot of antigen primarily at the site of application from which the antigen is released during a variable period
Increased uptake of antigen into APCs

Induction of synthesis and secretion of enhancing factors, such as cytokines.

Adjuvant activity

Facilitation of antigen transport, uptake and presentation by antigen-capturing and processing cells Repeated or prolonged release of antigen (depot effect) Signaling of receptors activating innate immune cells to release cytokines which upregulate co-stimulatory molecules Danger signals from stressed or damaged tissues activate APCs Signaling by recombinant cytokines or co-stimulatory molecules mimics classical adjuvant activity

Immunotherapy preformed Ab
Immune serum globulin (gammaglobulin) contains immunoglobulin extracted from the pooled blood of at least 1,000 human donors Treatment of choice for preventing measles, hepatitis A and replacing Ab in the immune deficient Lasts 2-3 months

Immunotherapy preformed Ab
Specific immune globulin- prepared from

convalescent patients in a hyperimmune state Contains high titer of specific Ab pertussis, tetanus, chickenpox, hepatitis B sera produced in horses are available for diphtheria, botulism, spider and snake bites act immediately and can protect patients for whom no other useful medication exists

Effectors functions of antibodies

Neutralization
reduce the pathogen load prevent contacts with host cell

Cell

Inhibit bacterial toxins

Complement mediated lyses

inhibits the pathogen penetration of the host cell

Complement binding pathogen destruction

Antianthracis gamma-globulin
Content: preparation contains

antitoxins. It is gammaglobulins fraction of serum of the hyperimmunized animals. There is the diminished amount of ballast matters in such preparation, that diminishes probability of development of by-reactions, above all things allergic substantially

What type of immunity (originally) is created in an organism after introduction?

Passive Humoral Antibacterial General Specific

Antidiphtherial antitoxic serum

Content: preparation is got

by hyperimmunization of horse a diphtherial toxoid. Effective mean of specific therapy of diphtheria. At the use it should be remembered rules of introduction of heterogenic serum, to eliminate development of anaphylactic shock and serum illness.

What type of immunity (originally) is created in an organism after introduction?

Passive Humoral Antibacterial General Specific

Sources of Passive Immunity

Almost all blood or blood products Homologous pooled human antibody (immune globulin) Homologous human hyperimmune globulin Heterologous hyperimmune serum (antitoxin)

Classification the serum preparations

homogeneous serum: serum obtained from blood donor volunteers, have been immunized. heterogeneous serum: serum obtained from blood of animals hyperimmunized.

Hypersensitivity reactions by injection of the heterogeneous serum

Anaphylactic shock
Type I, or anaphylactic, react ions often occur within 2 to 30 minutes after a person sensitized to an antigen is reexposed to that antigen. Anaphylaxis means opposite of protected," from the prefix ana-, meaning against, and the Greek phylaxis, meaning protection. Anaphylaxis is an inclusive term for the reactions caused when certain antigens combine with IgE antibodies. Anaphylactic responses can be systemic reactions, which produce shock and breathing difficulties and are sometimes fatal, or localized reactions, which include common allergic conditions such as hay fever, asthma, and hives (slightly raised, often itchy and reddened areas of the skin).

Serum Sickness
This is a systemic form of hypersensitivity of immediate reaction. It appears 7 to 12 days following single injection of high concentration of foreign serum
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The mechanism of anaphylaxis

IgE antibodies, produced in response to an antigen (heterogenic antibody), coat mast cells and basophils. When an antigen bridges the gap between two adjacent antibody molecules of the same specificity, the cell under goes degranulation and releases histamine and other mediators.

Bezredka method
Bezredka method (A.M. Bezredka, a microbiologist, was born in Russia, worked in France, 1870-1940) - a specific method of desensitization of the body that is used to prevent complications after the administration of heterogeneous serums.

Bezredka method
Heterologous hyperimmune sera (eg, antibotulinum, antitetanus, etc.) are highly concentrated; for desensitization recommended minimum dose. While under the influence of serum antigen occurs, neutralizing antibodies, fixed on the cell surface, and a decline in blood concentrations of physiologically active substances (histamine, etc.) that prevents the development of complications after reintroduction of the antigen.

Thank you for your attention!