1. CONTROL OF VIRAL DISEASES BY IMMUNIZATION

2. Introduction
Following an initial encounter with a pathogen, memory immune cells are established.
Reexposure to that same pathogen reawakens these memory cells to control the secondary infection quickly and prevent subsequent disease.
For many centuries, the illness that accompanied a primary infection was unavoidable, and for diseases such as smallpox, infected people often did not survive to face a second exposure.

3. Introduction
The goal of vaccination is to trigger an immune response more rapidly and with less harm than a natural infection:
essentially, to avoid the disease that often accompanies the first exposure while enabling establishment of long-lasting immunological memory
Vaccines against viral and bacterial pathogens prevent catastrophic losses of life in humans, other animals, and plants, and are considered among the greatest public health achievements

4. The Origins of Vaccination
The vaccination story begins with Dr. Edward Jenner, one day he overheard a dairymaid commenting that she would never get smallpox because she had been previously infected with cowpox
Jenner put this statement to the test on May 14, 1796, when he injected fluid from a cowpox lesion on the finger of a worker under the skin of a healthy 8-year-old boy.
As expected, the boy developed a fever and a lesion typical of cowpox at the site of the injection.

5. The Origins of Vaccination
Two weeks later, Jenner then deliberately infected the boy with smallpox. The young boy survived this potentially lethal challenge.
Nevertheless, the smallpox vaccine was put into widespread use in 1800, and the disease was declared eradicated by the WHO in 1979.
It took more than a century before the next practical vaccine for a viral disease appeared.
Louis Pasteur in 1884 prepared a rabies vaccine from the dehydrated spinal cord of an infected rabbit, and introduced the term vaccination.

6. The Origins of Vaccination
Other antiviral vaccines were slow to follow, largely because viruses were difficult to identify, propagate, and study.
Consequently, the next vaccines (against yellow fever and influenza viruses) did not appear until the mid-1930s.

7. Vaccine Basics Immunization Can Be Active or Passive
Active immunization
with attenuated or killed virus preparations or with purified viral proteins induces immunologically mediated resistance to infection or disease.
Passive immunization
introduces components of the immune response (e.g., antibodies or stimulated immune cells) obtained from an appropriate donor(s) directly into the patient.

8. Vaccine Basics
All neonates benefit from passive immunization following birth, as some of the mother’s antibodies pass into the fetal bloodstream via the placenta to provide transient protection to the immunologically naïve newborn
The best-known instance is for rabies, in which a preparation of human immunoglobulin is delivered as soon as possible after a bite from a rabid animal to contain the virus before it can be disseminated.

9. Immune Responses to Viral Infections
Immunity against viral infections is of 2 main types:
Active and passive
In active immunity
The infected, or vaccinated individual’s immune system take over the immune response.
In passive immunity
The infected individual receives antibodies or cells, the products of other individuals' reaction to viral infection.

11. I. Active immunity
Vaccines work because they educate the host’s immune system to recall the identity of a specific virus years after the initial encounter, a phenomenon called immune memory
Immune memory is maintained by dedicated T and B lymphocytes that remain after an infection has been resolved and most activated immune cells have died.
These memory cells are able to respond quickly to a subsequent infection.
Antiviral vaccines establish immunity and memory without the pathogenic effects typical of the initial encounter with a virulent virus.

12. I. Active immunity
Ideally, an effective vaccine is one that induces and maintains significant concentrations of memory cells in serum or at points of viral entry, such as mucosal surfaces and skin.
When the pathogen to which they are specific returns, the memory B and T cells spring to action, releasing an aggressive response that rapidly controls the pathogen before pathogenesis can ensue.

13. Vaccines
A vaccine is a biological preparation that provides active acquired immunity to a particular disease.
Features of a good vaccine
Ability to stimulate the appropriate immune response for the particular pathogen
Long term protection, ideally life-long
Safety, vaccine itself should not cause disease
Stable, retain immunogenicity, despite adverse storage conditions prior to administration
Inexpensive

14. Types of Vaccines There are 3 basic approaches to produce vaccines:
Subunit vaccines
Inactivated vaccines
Live (attenuated) virus vaccines

15. Subunit vaccines

16. A- Subunit Vaccines
A vaccine may consist of only a subset of viral proteins, as demonstrated by the highly successful hepatitis B vaccine.
Vaccines formulated with purified components of viruses, rather than the intact particles, are called subunit vaccines
Safe, well-defined vaccine, in which reversion or contamination with infectious virus is impossible.
To date, however, peptide vaccines have had little success, mainly because synthetic peptides are expensive to make in sufficient quantity, and the antibody response they elicit is often weak and short-lived.
Selection of escape mutants is highly probable.

17. A- Subunit Vaccines Synthetic vaccines Recombinant vaccines
Not very effective.
Great potential.
None currently in use
Recombinant vaccines
Better than synthetic vaccines
some success has already been achieved
HBV-now produced in yeast.

18. Production of subunit vaccine by recombinant DNA technology.

19. A- Subunit Vaccines Virus vectors
An attenuated virus is used to introduce microbial DNA to cells of the body.
“Vector” refers to the virus used as the carrier.

20. B. Inactivated vaccines
To prepare such a vaccine, virulent virus particles are isolated and inactivated by chemical or physical procedures.
These treatments eliminate the infectivity of the virus, but not its antigenicity (i.e., the ability to induce the desired immune response).
Common methods to inactivate virions include treatment with formaldehyde or β-propriolactone, dry or vapour heat.
These vaccines are safe for immunodeficient individuals, as the treated viruses cannot reproduce.
Immunization by inactivated vaccines, however, often requires the administration of multiple doses, as the first dose is generally insufficient to produce a protective response.

21. B. Inactivated vaccines
Advantages:
More effective than Subunit Vaccines – better immunogens.
Stable.
Little or no risk (if properly inactivated).
Disadvantages:
Not possible for all viruses;
denaturation may lead to loss of antigenicity, e.g., measles.
Not as effective at preventing infection as live viruses
May not protect for a long period?

22. C. Live (attenuated) virus vaccines
Replication-competent, attenuated vaccines are effective for at least two reasons.
Progeny virus particles are generally restricted to tissues around the site of inoculation, and this focal restriction generally results in mild or inapparent disease.
However, the limited virus reproduction stimulates a potent and lasting immune response.
Attenuated (less virulent) viruses are selected by growth in cells other than those of the normal host or by propagation at nonphysiological temperatures.

23. C. Live (attenuated) virus vaccines
Viruses specific for humans may become attenuated by passage in nonhuman cell lines.

24. Construction of attenuated viruses by using recombinant DNA technology.