This document summarizes key aspects of vaccine development and production. It discusses the types of vaccines including live-attenuated, inactivated, subunit, recombinant peptide, DNA, and viral vector vaccines. Production involves growing microorganisms or cells, purification, formulation with adjuvants or stabilizers, characterization, storage, and licensing. New technologies aim to develop vaccines for diseases lacking vaccines, and improve safety, efficacy, and heat stability of existing vaccines.
Types of Vaccines with live attenuated, inactivated up to recombination technique. OPV and IPV difference and rationale to replace OPV with IPV. EPI schedule of nepal
Types of Vaccines with live attenuated, inactivated up to recombination technique. OPV and IPV difference and rationale to replace OPV with IPV. EPI schedule of nepal
SYNTHETIC PEPTIDE VACCINES AND RECOMBINANT ANTIGEN VACCINED.R. Chandravanshi
What is a Vaccine?
A vaccine is a substance that is introduced into the body to prevent infection or to control disease due to a certain pathogen (a disease-causing organism, such as a virus, bacteria or parasite). The vaccine “teaches” the body how to defend itself against the pathogen by creating an immune response.
1 Unlike traditional pharmaceuticals, vaccines are biologics since they are made from living organisms (biological sources).
2 Specifically, vaccines are preparations of components derived from (or related to) a pathogen; they can typically induce a protective effect through one to three very small doses, in the range of micrograms to milligrams.
3 Immunity lasts for an extended period, from one year up to lifetime protection, including prevention of disease and/or related sequelae.
Synthetic peptide vaccines represent fragments of protein antigen sequences, synthesizing specific B cell and T cell epitopes offer the potential to induce diseases neutralizing immuno response with completely synthetic structure. Now it is well established that short chain peptides can be used to mimic antigenic sites of viruses and thus can be used the basics for vaccines and development. therefore, attempts have been made to synthesize such peptides which act as the serrogate immuunogens, as an alternative to the existing conventional vaccines.
A introduction on Viral vaccine for medical students.Although most attenuated vaccines are viral, some are bacterial in nature. Examples include the viral diseases yellow fever, measles, rubella, and mumps, and the bacterial disease typhoid.
A vaccine is a biological preparation that provides active acquired immunity to a particular infectious disease. A vaccine typically contains an agent that resembles a disease-causing microorganism and is often made from weakened or killed forms of the microbe, its toxins, or one of its surface proteins.
A vaccine is a biological preparation of weakened or killed pathogen such as bacterium or virus that will improves immunity to a particular diseases.
The principle of immunization or vaccination is based on the property of ‘memory’ of the immune system.
The process of introduction of vaccine into an individual to provide protection against a disease called vaccination.
Humoral immunity is defined as the immunity mediated by antibodies, which are secreted by B lymphocytes.
B lymphocytes secrete the antibodies into the blood and lymph
BP-605T, Pharmaceutical biotechnology, Structure of immunoglobulins, classification of immunoglobulins, explanation of structure of immunoglobulin, digestion with proteolytic enzymes, Fab region, Fc region, role of different immunoglobulin classes, structure of IGM, IGA, IGG, IGE, IGD, Light chain, heavy chain, kappa, lambda, papain enzyme, pepsin enzyme
vaccine is a biological preparation that provides active acquired immunity to a particular disease. A vaccine typically contains an agent that resembles a disease-causing microorganism and is often made from weakened or killed forms of the microbe, its toxins, or one of its surface proteins. The agent stimulates the body's immune system to recognize the agent as a threat, destroy it, and to further recognize and destroy any of the microorganisms associated with that agent that it may encounter in the future.
HISTORY OF VACCINES-
EDWARD JENNER conduct experiments in 1796 that lead to the creation of the first smallpox vaccine for prevention of smallpox.
A vaccine for RABIES is developed by LOUIS PASTEUR .
Vaccine for COLERA and TYPHOID were developed in 1896 and PLAGE vaccine in 1887.
The first DIPHTHERIA vaccine is developed in about 1913 by EMIL ADOLPH BEHRING,WILLIAM HALLOCK PARK.
The whole cell PERTUSIS vaccines are developed in 1914.
A TETANUS vaccine is developed in 1927.
SYNTHETIC PEPTIDE VACCINES AND RECOMBINANT ANTIGEN VACCINED.R. Chandravanshi
What is a Vaccine?
A vaccine is a substance that is introduced into the body to prevent infection or to control disease due to a certain pathogen (a disease-causing organism, such as a virus, bacteria or parasite). The vaccine “teaches” the body how to defend itself against the pathogen by creating an immune response.
1 Unlike traditional pharmaceuticals, vaccines are biologics since they are made from living organisms (biological sources).
2 Specifically, vaccines are preparations of components derived from (or related to) a pathogen; they can typically induce a protective effect through one to three very small doses, in the range of micrograms to milligrams.
3 Immunity lasts for an extended period, from one year up to lifetime protection, including prevention of disease and/or related sequelae.
Synthetic peptide vaccines represent fragments of protein antigen sequences, synthesizing specific B cell and T cell epitopes offer the potential to induce diseases neutralizing immuno response with completely synthetic structure. Now it is well established that short chain peptides can be used to mimic antigenic sites of viruses and thus can be used the basics for vaccines and development. therefore, attempts have been made to synthesize such peptides which act as the serrogate immuunogens, as an alternative to the existing conventional vaccines.
A introduction on Viral vaccine for medical students.Although most attenuated vaccines are viral, some are bacterial in nature. Examples include the viral diseases yellow fever, measles, rubella, and mumps, and the bacterial disease typhoid.
A vaccine is a biological preparation that provides active acquired immunity to a particular infectious disease. A vaccine typically contains an agent that resembles a disease-causing microorganism and is often made from weakened or killed forms of the microbe, its toxins, or one of its surface proteins.
A vaccine is a biological preparation of weakened or killed pathogen such as bacterium or virus that will improves immunity to a particular diseases.
The principle of immunization or vaccination is based on the property of ‘memory’ of the immune system.
The process of introduction of vaccine into an individual to provide protection against a disease called vaccination.
Humoral immunity is defined as the immunity mediated by antibodies, which are secreted by B lymphocytes.
B lymphocytes secrete the antibodies into the blood and lymph
BP-605T, Pharmaceutical biotechnology, Structure of immunoglobulins, classification of immunoglobulins, explanation of structure of immunoglobulin, digestion with proteolytic enzymes, Fab region, Fc region, role of different immunoglobulin classes, structure of IGM, IGA, IGG, IGE, IGD, Light chain, heavy chain, kappa, lambda, papain enzyme, pepsin enzyme
vaccine is a biological preparation that provides active acquired immunity to a particular disease. A vaccine typically contains an agent that resembles a disease-causing microorganism and is often made from weakened or killed forms of the microbe, its toxins, or one of its surface proteins. The agent stimulates the body's immune system to recognize the agent as a threat, destroy it, and to further recognize and destroy any of the microorganisms associated with that agent that it may encounter in the future.
HISTORY OF VACCINES-
EDWARD JENNER conduct experiments in 1796 that lead to the creation of the first smallpox vaccine for prevention of smallpox.
A vaccine for RABIES is developed by LOUIS PASTEUR .
Vaccine for COLERA and TYPHOID were developed in 1896 and PLAGE vaccine in 1887.
The first DIPHTHERIA vaccine is developed in about 1913 by EMIL ADOLPH BEHRING,WILLIAM HALLOCK PARK.
The whole cell PERTUSIS vaccines are developed in 1914.
A TETANUS vaccine is developed in 1927.
INTRODUCTION OF VACCINE & VACCINATION.
HISTORY.
TYPRE OF VACCINE
CONTRAINDICATION.
CLASSIFICATION ACCORDING TO PATHOGEN.
PRECAUTION BEFORE TO VACCINE.
DRUGS ADMINISTRATION -: ROUTES & DOSE
SUMMARY.
REFERENCES.
ASSESSMENT QUESTIONS
vaccine train user immune system to create antibodies, just as it when it is exposed to a disease. However, because vaccine contain only killed or weakened forms of germs like viruses or bacteria, they do not cause the disease or put you at the risk of complications.
vaccine is a biological preparation that improve immunity to a particular disease.
A vaccine typically contain an agent that resembles a disease causing microorganisms and is often made from weakened or killed forms of the microbes.
Immunity: Protection from an infectious disease. If you are immune to a disease, you can be exposed to it without becoming infected.
Vaccine: A preparation that is used to stimulate the body’s immune response against diseases. Vaccines are usually administered through needle injections, but some can be administered by mouth or sprayed into the nose.
Vaccination: The act of introducing a vaccine into the body to produce protection from a specific disease.
Most developments in biotechnology originated for their potential applications in health care.
Contributions of biotechnology are more frequent, more notable and more rewarding in health sector.
3. Introduction
Vaccine applies to all biological preparations, produced from
living organisms , that enhance immunity against disease .
Vaccination is a medical strategy whose main aim is to prevent
infectious diseases.
It’s a rapidly evolving field which requires-
-Development of vaccines for diseases against which no
vaccine is available.
- Improvement in existing technology
4. Ideal Vaccine
Is 100% efficient in all individuals of any ages
Provides life long protection after single administration
Does not evoke adverse reaction
Is available in unlimited quantites
Is stable under various conditions (temperature, light ,
transportation)
Is easy to administer
Is cheap
5. Immunological Principles of Vaccination
After recovery from the disease, the immunological response
indeed to protect us from that disease . This phenomenon is
called immunity.
Active immunity established before infection. It stimulates
humoral and cellular immune response both the aim of
protecting against a pathogen.
Passive immunity has been applied for prevention and therapy
of infectious diseases. It is preparation of Abs, protect against a
pathogen and is administrated before , at or around the time of
known or potential exposure.
6. Immunity induced must be robust and durable .
Immunological mechanisms:
i) Protective antibodies
ii) T cells responses: CD4 + helper T cells enhance antibody
response while anti bodies exeract significant influences on
T cell responses to intracellular pathogens and formation of
memory cells.
12. Advantages and Disadvantages
Advantages :-
Raises immune response to all protective antigens.
More durable immunity therefore fewer and low doses are
required.
Quick Immunity in majority of vaccines.
Disadvantages :-
But these live vaccines bear the risk that the nucleic acid is
incorporated into the hosts genome.
Also chances of mutation and reversion to virulence is high.
14. Non Living Vaccines(inactivated)
Inactivation of whole bacteria or virus using reagents like
formaldehyde or providing heat.
Examples:-
-Influenza -Tetanus
-Diphtheria -Old pertussis
-HPV Polysaccharide -Hepatitis A
-Conjugated (Men C) -Poliovirus
-Old typhoid
15.
16. Second Generation Vaccines
SUBUNIT VACCINES
Toxoid Vaccines:-
Pathogenic toxin is modified to harmless toxoid.
Immunogenicity of toxoid is less so a combination of
antibodies and toxoid is given.
Adjuvents are also added.
Ex. Tetanus Toxoid vaccine.
BCG
17. ACCELULAR PERTUSSIS VACCINE:-
These vaccines are prepared by extraction of bacterial
suspensions followed by purification to prepare a cell free
culture suspension.
POLYSACCHARIDE VACCINES:-
Protective immunity to encapsulated bacteria involves an
antibody response to a polysaccharide (PS) antigen,
interactions with T and B lymphocytes, and host defense
mechanisms. PS vaccines developed against Neisseria
meningitides, Streptococcus pneumoniae, Haemophilus
influenza type b, and Salmonella typhi, prevent infection
by inducing an immune response against specific capsular
polysaccharides.
18. Third generation Vaccines
Genetically Improved Live Vaccines:-
While attenuating microorganisms genetically, certain
factors should be noted-
Virulence and the life cycle of the pathogen have to be
studied in detail.
Attenuation must not result in reduced immunogenicity.
Steps should be taken to prevent reversion .
Homologous Genetic engineering approach used.
19. Example: Cholera Vaccine
An effective cholera vaccine should induce a local,
humoral response in order to prevent colonization of small
intestine. Initial trials with Vibrio cholera toxin (CT)
mutants caused mild diarrhoea.Which was caused by
expression of accessory toxin.
Therefore, a natural mutant was isolated that was negative
for toxins. Next, CT was detoxified using rDNA
technology.
The resulting vaccine strain CVD 103 is well tolerated by
children.
20. Live Vectors(attenuated)
A way to improve the safety or efficacy of vaccines is
using live harmless viruses or bacteria as carriers for
antigens from other pathogens. These are called
vectors.
Advantages include safety in humans as there is no
risk of pathogenicity.
Possibility for multiple immunogenic expression
Relatively heat resistance.
21.
22. Proteins Expressed in host cells
Protein based vaccines are sometimes expressed by host
cells of the same species(homologous) or different
species(heterologous) to allow high expression level
Heterologous hosts used for the expression of
immunogenic proteins include yeasts , bacteria and
mammalian cell lines.
Hepatitis B surface antigen(HBaAg), which previously
was obtained from plasma of infected individual, has been
expressed in baker’s yeast and in mammalian cells.
23. Then transforming the host cell with a plasmid containing
the HBsAg encoding gene.
Both the expression system yield 22 nm HBsAg particles
that are identical to those excreted by the native virus.
Multiple antigens are also expressed in homologous host
cells as in the case of Meningococcal vesicle vaccine.
24. Recombinant Peptide vaccines
Recombinant peptide vaccines consist of protein antigen
that have been produced in heterologous expression
system.
The vaccinated person produces antibodies to the protein
antigen, thus protecting him/her from disease.
Genetic fusion of peptides with proteins offers the
possibility to produce protective epitopes of toxic antigens
derived from pathogenic species as part of non-toxic
proteins expressed by harmless species.
28. Anti-idiotypic vaccine
Anti-idiotypic vaccines comprise antibodies that have
three-dimensional immunogenic regions,
designated idiotopes, that consist of protein sequences that
bind to cell receptors. Idiotopes are aggregated
into idiotopes specific of their target antigen.
Antibodies that bind tumor-associated antigens (TAA) are
isolated and injected into mice.
To the murine immune system, the TAA antibodies are
antigens and cause an immunogenic reaction producing murine
antibodies that can bind to the "TAA idiotype" and is said to be
"anti-idiotypic".
29.
30. Synthetic Peptide Vaccine
Synthetic peptides exhibit molecular mimicry which helps
in vaccine design.
The conformational epitopes of these peptides in B cells
are determined.
These synthetic peptides can be prepared in unlimited
qualities and are not majorly toxic.
The conformation of the peptide is very important and if
this is disturbed, then the antibodies can’t recognize the
peptides.
Ex. Tetanus vaccine
32. Nucleic Acid Vaccines
DNA sequence used as a vaccine.
This DNA Sequence code for antigenic protein of
pathogen.
As this DNA inserted into cells it is translated to form
antigenic protein. As this protein is foreign to cells , so
immune response raised against this protein.
In this way ,DNA vaccine provide immunity against that
pathogen.
33. Advantages:-
Uses only the DNA from infectious organisms.
Avoid the risk of using actual infectious organism.
Provide both Humoral & Cell mediated immunity.
Disadvantages:-
Limited to protein immunogen only
Extended immuno stimulation leads to chronic
inflammation
Some antigen require processing which sometime
does not occur
35. How DNA Vaccine works
By two pathways :-
1)Endogenous:-Antigenic Protein is presented by cell in
which it is produced.
2)Exogenous:- Antigenic Protein is formed in one cell
but presented by different cell.
36.
37.
38.
39. Current Clinical Trials
June 2006,DNA vaccine examined on horse
Horse acquired immunity against west
nile viruses
August 2007,DNA vaccination against multiple
Sclerosis was reported as being effective
41. Production
Expect for synthetic peptides, vaccines are derived from
micro-organisms or animal cells. These cells can be
genetically modified.
Animal cells are used for the cultivation of viruses and for
the production of some subunit vaccine component.
Three stages can be discerned in manufacture of cell
derived vaccines:-
-Cultivation
-downstream processing
-formulation
50. Formulation
Vaccine formulation may include buffer components,
salts, preventives and stabilizers. These addition should
not adversely affect vaccine components upon addition,
storage and application.
Preventives used include thimersoal, phenoxyethanol,
phenol and antibiotics.
Formaldehyde which is used as inactivating agent of
toxins and poliovirus as stabilizers of vaccine
components.
This may prevent their degradation by low pH and lytic
enzymes in gastrointestinal tract.
51.
52. Adjuvants
Adjuvants are defined as any material that can increase the
humoral and cellular response against an antigen.
Colloidal aluminium salts(hydroxide , phosphate) are
widely used in many classical vaccine formulations.
Other adjuvants are in experimental testing or are
sometimes used in veterinary vaccines.
Delivery systems are injectable devices that allow devices
that allow multi-meric presentation of antigens.
54. Delivery System Characteristics
EMULSIONS Both water-in-oil and oil-in-water
emulsions are used ; often contain
amphiphilic adjuvants
LIPOSOMES Phospholipids membrane vesicles ;
aqueous interior as well as lipid bilayer
may contain antigens and adjuvants
ISCOMs Miscellar lipid-saponin complex ; not
suitable for soluble antigens
MICROSPHERES Bio-degradable polymeric spheres,
often poly(lactide-co-glycolide)
NBP Non-ionic block co-polymers
55. Mechanisms proposed for adjuvant action
include
1) Slow release of the antigens
2)Attraction and stimulation of macrophages and
lymphocytes
3)Delivery of the antigen to regional lymph nodes.
56. Combination Vaccines
Combination vaccine components may create
pharmaceutical as well as immunological problems.
For instance, formaldehyde containing components may
chemically react with other components;(e.g. n DTP
vaccine) is incompatible with IPV.
Therefore e not be combination vaccines containing the
polio component.
To this end , dual-chamber syringes have been developed ,
e.g. for TP-IPV(Sawyer et al.,1994).
57. Characterization
Column chromatographic(HPLC) and electrophoretic
techniques like electrophoresis and capillary provide
information about the purity, molecular weight and
electrical charge of the vaccine component.
The use of bio-sensors makes it possible to measure
antigen-antibody interactions momentarily, allowing
accurate determination of binding kinetics and affinity
constants.
58. Storage
Depending on their specific characteristics , vaccines are
stored in solution or in freeze-dried formulation , usually
at 2-8`C.
The shelf-life depends on the physico-chemical of the
vaccine formulation and on the storage conditions and
typically is in the order of several years.
59. Regulatory and clinical Aspects
Vaccine manufactures need a license to produce and
distribute a vaccine. This license is issued by the national
authority after inspection of the production facilities
review of the production process as well as efficacy and
safety data.
The vaccine lot is released for application derived in
humans if both production data and those of the controls
are in accordance with the specification derived from the
requirements.
64. Licensing and Trials
Licensing is preceded by premarketing stage.
Field studies in man are crucial which are divided into
three phasic trials.
In phase I ,major side effects are studied in small number
of healthy subjects.
In phase II, desired immune response and relative safety
are investigated in a larger group of people.
In phase III, efficacy and safety of the vaccine is
evaluated.
65. Conclusion
There are still many viral and parasitic, diseases against
which no effective vaccine exists. In addition , the
growing resistance to the existing arsenal of antibiotics
increases the need to develop vaccines against common
bacterial infections.
It expected that novel vaccines against several of these
diseases will become available and in these cases several
technologies described in this paper have great promise.
66. References
http://immunologyanimation.hpa.org.uk/
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Stuve O, Eagar TN, Frohman EM, Cravens PD. 2007. DNA
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