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Lec 10
Virology
A Vaccine is a biological preparation that enhances immunity to a
particular disease.
*Introduction
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 produce specific antibodies or a cellular immune response that destroys or neutralizes the
microorganism or its toxins. Immunization against hepatitis A and B,
diphtheria, tetanus, pertussis, Haemophilus influenzae type b (Hib),
polio, rotavirus, measles, mumps, rubella, varicella-zoster virus (VZV),
pneumococcus, influenza, meningococcus, and human papillomavirus.
*Types of vaccines :
Vaccines are
1- live, attenuated microorganisms: When live pathogens are used,
they are attenuated (weakened) to preclude clinical consequences of
infection. Attenuated microbes reproduce in the recipient, typically
leading to a more robust and long-lasting immune response than can be
obtained through vaccination with killed organisms . For example,
vaccine-associated poliomyelitis occurs following administration of
approximately 1 of every 2.4 million doses of live polio vaccine
2- killed microorganisms: Killed vaccines have the advantage over
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attenuated microorganisms in that they pose no risk of vaccine-associated
infection. As noted above, killed organisms often provide a weak or
short-lived immune response.
3- microbial extracts: Instead of using whole organisms, vaccines
can be composed of antigen molecules (often those located on
the surface of the microorganism) extracted from the pathogen or
prepared by recombinant DNA techniques
4-vaccine conjugates : H. influenza polysaccharide vaccine
does not provide protection for children ages 3 to 18 months.
Consequently, this organism has, in the past, produced severe
infections in this age group. However, by covalent conjugating the
Haemophilus polysaccharide to a protein antigen, such as
diphtheria toxoid, H. influenzae vaccines produce a robust
T cell–dependent antibody response even in 3-month-old infant
5- inactivated toxins (toxoids). Both bacterial and viral pathogens are
targeted by these diverse mean. These are derivatives of bacterial
exotoxins produced by chemically altering the natural toxin or by
engineering bacteria to produce harmless variants of the toxin.
6- DNA vaccines:
represent a new approach to vaccination. The proposed
mechanism for these vaccines is that the gene for the antigen of interest is
cloned into a bacterial plasmid, which is engineered to increase
the expression of the inserted gene in mammalian cells.
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*Types of immune response to vaccines
Vaccines containing killed pathogens (such as hepatitis A or the Salk
polio vaccine) or antigenic components of pathogens (such as hepatitis B
subunit vaccine) do not enter host cells, thereby eliciting a primary B
cell mediated humeral response. These antibodies are ineffective in
attacking intracellular organisms. By contrast, attenuated live vaccines
(usually viruses) do penetrate cells. This results in the production of
intracellular antigens that are displayed on the surface of the infected cell,
prompting a cytotoxic T-cell response, which is effective in eliminating
intracellular pathogens.
*The preparation of a vaccine:
Production of vaccine can be divided in the following steps:
1. Generation of the antigen
The first step in order to produce a vaccine is generating the antigen that
will trigger the immune response. For this purpose the pathogen’s
proteins or DNA need to be grown and harvested using the following
mechanisms:
Viruses are grown on primary cells such as cells from chicken embryos or
using fertilised eggs (e.g. influenza vaccine) or cell lines that reproduce
repeatedly (e.g. hepatitis A)
Recombinant proteins derived from the pathogen can be generated
either in yeast, bacteria or cell cultures.
2. Release and isolation of the antigen:
The aim of this second step is to release as much virus or bacteria as
possible. To achieve this, the antigen will be separated from the cells and
isolated from the proteins and other parts of the growth medium that are
still present.
3. Purification
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In a third step the antigen will need to be purified in order to produce a
high purity/quality product. This will be accomplished using different
techniques for protein purification. For this purpose several separation
steps will be carried out using the differences in for instance protein size,
physico-chemical properties, binding affinity or biological activity.
4. Addition of other components
The fourth step may include the addition of an adjuvant, which is a
material that enhances the recipient’s immune response to a supplied
antigen. The vaccine is then formulated by adding stabilizers to prolong
the storage life or preservatives to allow multi-dose vials to be used safely
as needed. Due to potential incompatibilities and interactions between
antigens and other ingredients, combination vaccines will be more
challenging to develop. Finally, all components that constitute the final
vaccine are combined and mixed uniformly in a single vial or syringe.
5. Packaging
Once the vaccine is put in recipient vessel (either a vial or a syringe), it is
sealed with sterile stoppers.. Finally, the vaccine is labeled and
distributed worldwide.
Routes of administration of vaccine :
1- Intramuscular (IM) injection administers the vaccine into the muscle mass.
Vaccines containing adjuvants should be injected IM to reduce adverse local effects.
2-Subcutaneous (SC) injection administers the vaccine into the subcutaneous layer
above the muscle and below the skin.
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3-Intradermal (ID) injection administers the vaccine in the topmost layer of the
skin. BCG is the only vaccine with this route of administration. Intradermal injection
of BCG vaccine reduces the risk of neurovascular injury.
4-Oral administration of vaccine makes immunization easier by eliminating the
need for a needle and syringe.
5-Intranasal spray application of a vaccine offers a needle free approach through
the nasal mucosa of the vaccine
*Viral vaccines
Immunity to viral infection requires an immune response to antigens
located on the surface of the viral particles or on virus-infected cells. For
enveloped viruses, these antigens are often surface glycoproteins. The
main limitation of viral vaccines occurs with viruses that show a
genetically unstable antigenicity (that is, they display antigenic
determinants that continuously vary, such as with influenza viruses or the
human immunodeficiency virus [HIV].
Common viral pathogens for which there are vaccines include the
following.
A. Hepatitis A
Formalin-inactivated whole virus vaccine produces antibody levels in
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adults similar to those observed following natural infection and is not
recommended for children younger than age 2 years because
residual anti-hepatitis A passively acquired from the mother may
interfere with vaccine immunogenicity.
B. Hepatitis B
The current vaccine contains recombinant hepatitis surface antigen.
C. Varicella zoster
This vaccine contains live, attenuated, temperature-sensitive
Varicella zoster virus. Its efficacy in preventing chickenpox is
approximately 85 to 100 percent in children.
D. Polio
Vaccine of poliomyelitis is include first the inactivated polio vaccine
called (Salk vaccine ,take by injection )and second the live,
attenuated(Sabin vaccine, take orally) it provides life-long protection
from poliovirus for more than 95 percent of recipient after the primary
three-dose series, and 3) it provides early GI immunity . administered
polio vaccine have established efficacy in preventing poliovirus infection
and paralytic poliomyelitis
E. Influenza
The traditional “flu shot” vaccine contains formalin-inactivated virus.
A live, attenuated influenza vaccine is administered intranasally.
F. Measles, mumps, and rubella
This combination vaccine contains live, attenuated virus and should
be administered to young children prior to entering school. Measles
vaccine should also be administered to individuals traveling in
endemic areas
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J. Human papillomavirus vaccine:
Human papillomavirus (HPV) vaccine is recommended for routine
administration in all children beginning at ages 11 to 12 years.
Quadrivalent HPV vaccine is the only vaccine approved for males
for protection against genital warts, and either Quadrivalent or
bivalent vaccine may be used in females for the protection against
cervical cancer and reducing the incidence of genital warts
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