VACCINES
The introduction of vaccination has been one of the most decisive advances leading to the dramatic downward trend in the incidence of many viral diseases.The principle of vaccination is to induce a “primed” state in the vaccinated subject so
that, following exposure to a pathogen, a rapid secondary immune response is generated leading to the accelerated elimination of the organism and protection from clinical disease. Success depends on the generation of memory T and B cells and the presence in the serum of neutralizing antibody.
Attributes of a good vaccine
• Ability to elicit the appropriate immune response for the particular pathogen:
Tuberculosis—cell mediated response
Most bacterial and viral infections—antibody
• Long term protection ideally life-long
• Safety vaccine itself should not cause disease
• Stable retain immunogenicity, despite adverse storage conditions prior to
administration
• Inexpensive
Types of Vaccine:
Vaccines in general use includes: LIVE vaccines; and KILLED vaccines
A. Live Vaccines
1. Live attenuated organisms whose virulence has been artificially reduced by in vitro culture under adverse conditions, such as reduced temperature. This results in the selection of mutants which replicate poorly in the human host and are therefore of reduced virulence. Replication of the vaccine strain in the host reproduces many of the features of wild type infection, without causing clinical disease. Most successful viral vaccines belong to this group.The immune response is usually good—when the virus replicates in the host cells,
both antibody as well as cell mediated immune responses are generated and
immunity is generally long lived. Often, only a single dose is needed to induce long
term immunity.
Potential drawbacks to these vaccines include: the danger of reversion to virulence and the possibility of causing extensive disease in immuno-compromised individuals.
2. Heterologous vaccines
Closely related organism of lesser virulence which shares many antigens with the
virulent organism. The vaccine strain replicates in the host and induces an immune response that cross reacts with antigens of the virulent organism. The most famous example of this type of vaccine is vaccinia virus: Both cowpox virus and vaccinia virus are closely related to variola virus, the causitive agent of smallpox. The
eighteenth centuary physician, Edward Jenner observed that milkmaids who had
been infected with cowpox virus were immune to smallpox. Widespread use of vaccinia virus as a vaccine has lead to the world-wide eradication of smallpox.
3. Live recombinant vaccines
It is possible, using genetic engineering, to introduce a gene coding for an immunogenic protein from one organism into the genome of another (such as vaccinia virus). The organism expressing a foreign gene is called a recombinant. Following injection intothe subject, the recombinant organism will replicate and express sufficient amounts of the foreign protein to induce a specific immune response to the protein.
B. Killed (inactivated) vaccines
1. When safe live vaccines are not available, either because attenuated strains have not
been developed or else because reversion to wild type occurs too readily, it may be
possible to use an inactivated preparation of the virulent organism to immunize the
host.
2. The organism is propagated in bulk, in vitro, and inactivated with either beta-
propiolactone or formaldehyde. These vaccines are not infectious and are therefore relatively safe. However, they are usually of lower immunogenicity and multiple doses may be needed to induce immunity. In addition, they are usually expensive to prepare Subcellular fractions
3. When protective immunity is known to be directed against only one or two proteins
of an organism, it may be possible to use a purified preparation of these proteins as a
vaccine. The organism is grown in bulk and inactivated, and then the protein of
interest is purified and concentrated from the culture suspension. These vaccines are
safe and fewer local reactions occur at the injection site. However, the same
disadvantages of poor immunogenicity and the need for multiple boosters apply.
C. Recombinant proteins
Immunogenic proteins of virulent organisms may be synthesized artificially by introducing the gene coding for the protein into an expression vector, such as E-coli or yeasts. The protein of interest can be extracted from lysates of the expression vector, then concentrated and purified for use as a vaccine. The only example of such a vaccine, in current use, is the hepatitis Bvaccine.
D. DNA Vaccines
DNA vaccines are at present experimental, but hold promise for future therapy since they will evoke both humoral and cell-mediated immunity, without the dangers associated with live virus vaccines. The gene for an antigenic determinant of a pathogenic organism is inserted into a plasmid.This genetically engineered plasmid comprises the DNA vaccine which is then injected into the host. Within the host cells, the foreign gene can be expressed (transcribed and translated) from the plasmid DNA, and if sufficient amounts of the foreign protein are produced, they will elicit an immune response.
E. Vaccines in general use
1. Measles: Live attenuated virus grown in chick embryo fibroblasts, first introducedin the 1960’s. In developed countries, the vaccine is administered to all children in
the second year of life (at about 15 months). If the vaccine is administered too early,
however, there is a poor take rate due to the interference by maternal antibody. Forthis reason, when vaccine is administered before the age of one year, a booster dose is recommended at 15 months.
2. Mumps: Live attenuated virus developed in the 1960’s. In first world countries it is
administered together with measles and rubella at 15 months in the MMR vaccine.
3. Rubella: Live attenuated virus. Rubella causes a mild febrile illness in children, but
if infection occurs during pregnancy, the foetus may develop severe congenital
abnormalities.
4. Polio: Two highly effective vaccines containing all 3 strains of poliovirus are in general use:
The killed virus vaccine (Salk, 1954) is used mainly in Sweden, Finland, Holland
and Iceland.
The live attenuated oral polio vaccine (Sabin, 1957) has been adopted in most
parts of the world; its chief advantages being: low cost, the fact that it induces mucosal immunity and the possibility that, in poorly immunized communities, vaccine strains might replace circulating wild strains and improve herd immunity.
The inactivated Salk vaccine is recommended for children who are
immunosuppressed.
5. Hepatitis B: Two vaccines are in current use: a serum derived vaccine and a
recombinant vaccine. Both contain purified preparations of the hepatitis B surface
protein. The serum derived vaccine is prepared from hepatitis B surface protein,
purified from the serum of hepatitis B carriers. This protein is synthesised in vast
excess by infected hepatocytes and secreted into the blood of infected individuals. A
second vaccine, produced by recombinant DNA technology, has since become available.
Three doses are given; at 6, 10, and 14 weeks of age. As with any killed viral vaccines, a booster will be required at some interval (not yet determined, but about 5 years) to provide protection in later life from hepatitis B infection as a venereal disease.
6. Hepatitis A: A vaccine for hepatitis A has been developed from formalin-inactivated,
cell culture-derived virus.
7. Varicella-Zoster virus: A live attenuated strain of varicella zoster virus has been
developed.








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