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Vaccinations
Vaccination is the intentional exposure to modified forms or parts of a pathogen that do not
cause disease
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So that it can rapidly mobilize its forms to fight infection when
required
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However, many people die each year
from vaccine preventable diseases due to lack of access to the vaccine or poor vaccine
uptake due to scientific ignorance within a society
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Passive immunity can be acquired naturally, eg
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Active immunity
Active immunity triggers the host's immune system, resulting in the production of antibodies
by the host as well as memory cells, thus active immunity is long lasting
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Active immunity can be
achieved by natural exposure to the infectious agent, or it can be acquired artificially by
administration of a vaccine
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Due to the development of the smallpox
vaccine, not a single naturally acquired smallpox case has been reported anywhere since
1977
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The danger of contracting the disease must be significantly worse than the
danger posed by a potential vaccine
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Problems with safety of non-living vaccines include; contamination by toxins or chemicals,
allergic reactions, and the induction of autoimmunity
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Factors determining
vaccine safety include; the incidence of disease, the incidence of adverse events of vaccine,
immunisation rates, and the availability and affordability of alternative vaccines
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The chance of a susceptible individual
contacting an infected individual is low
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Measles, mumps, and rubella vaccine
The measles, mumps, and rubella (MMR) vaccine is a live attenuated vaccine
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Children should be given two doses of the vaccine, as the first
dose fails to induce immunity in 5% of those vaccinated
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Vaccine induced
immunity to measles is long lived
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However the number
of measles cases increased in the UK post 2001, following reduced vaccine uptake
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However, the paper reporting this claim used an extremely small
sample size of 12 patients, and was later retracted, additionally further studies have failed to
show an increased risk of autism after the MMR vaccine
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It is
important to maintain the structure of key epitopes on surface antigens during inactivation
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Chemical
inactivation with formaldehyde or various alkylating agents is more successful
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Inactivated vaccines require repeated boosters to achieve a protective immune status
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Even though the pathogens they contain are
killed, inactivated vaccines still carry risks due to failure to follow proper inactivation
procedures
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Additional
advantages of inactivated vaccines include; stability and ease of storage and transport
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influenza,
hepatitis A, cholera, and polio
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This exposes the immune system to the live
pathogen
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Attenuation can be achieved by growing a
pathogenic bacterium or virus for prolonged periods under abnormal culture conditions
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Attenuates vaccines have obvious advantages
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This
results in increased immunogenicity and more efficient production of highly effective memory
cells
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The ability of
live vaccines to replicate within host cells makes them particularly suitable for inducing
cell-mediated responses
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The
major disadvantage of attenuated vaccines is that these live forms can sometimes mutate
and revert back to a more virulent form in the host
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Additionally, live
vaccines may be more biochemically, genetically, and biologically unstable than inactivated
vaccines
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One example of a live attenuated vaccine is the Sabin oral polio
vaccine (OPV)
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The attenuated viruses
colonize the intestine and induce production of secretory immunoglobulin A, a defense
against naturally acquired polio virus
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Unlike other attenuated vaccines, OPV requires boosters, because the
three strains of attenuated polio virus can interfere with each others replication in the
intestine, although subsequently developed mono- and divalent OPV don't have this
drawback
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The rate of reversion of the OPV to a virulent form is extremely
low; 1 in 2
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This is considered an acceptable risk in areas
where the danger from wild type polio is high, so risk of paralysis is high
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Subunit vaccine
Subunit vaccines use only specific, purified macromolecules derived from the pathogen
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Subunit vaccines are developed using recombinant DNA technology and
high resolution biochemical methods
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A number of genes encoding
surface antigens from viral, bacterial, and protozoan pathogens have also been successfully
cloned into cellular expression systems for use in vaccine development
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One limitation of some
subunit vaccines, especially polysaccharide vaccines, is their inability to activate T helper
cells
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This can be avoided in vaccines that conjugate a
polysaccharide antigen ti a protein carrier, which induces T helper cell responses against
both the protein and polysaccharide
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Some bacterial pathogens, including those that cause diphtheria and tetanus,
produce exotoxins that account for all of the disease symptoms resulting from infection
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Vaccination with the toxoid induces
anti-toxoid antibodies capable of binding the toxin and neutralising its effects
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Passive immunity can be used to provide temporary protection in unvaccinated individuals
exposed to organisms that express these exotoxins
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Coating the capsule with antibodies and/or complement greatly increases the ability
of macrophages and neutrophils of phagocytose such pathogens, thus providing the
rationale for vaccines consisting of purified capsular polysaccharides
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The vaccine induces formation of opsonizing antibodies
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Individual genes that encode key
antigens of especially virulent pathogens can be introduced into safe attenuated viruses or
bacteria that are used as live carriers
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Since most of the genome of the pathogen is missing, reversion potential
is eliminated
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This large complex virus, with a
genome of about 200 genes can be engineered to carry several dozen foreign genes without
impairing its capacity to infect host cells and replicate
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hen tissue culture cells are incubated
simultaneously with vaccinia virus and the recombinant plasmid, DNA encoding the antigen
is inserted into the vaccinia virus genome by homologous recombination at the site of
nonessential TK gene, resulting in a TK- recombinant virus
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Another vaccine
vector is an attenuated strain of the vesicular stomatitis virus (VSV), which has been
engineered with genes encoding the surface proteins of the Ebola virus
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Adjuvants
Adjuvants are substances that are added to vaccine preparations to enhance
immunogenicity
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When mixed with the
pathogen- associated antigens, adjuvants can also aid delivery of the vaccine to the immune
system and enhance general immune responsiveness
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Alum is a good enhancer of Th2 responses but a
weaker stimulator of Th1 pathways
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Recently developed adjuvants include virosome, a reconstituted virus envelope
containing phospholipids and virus glycoproteins but without any genetic information
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Virisome
may elicit a much greater cell-mediated immune response than alum alone
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