CONTROL OF VIRAL DISEASES BY IMMUNIZATION

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.

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

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.

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.

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.

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.

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.

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.

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.

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.

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

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

Subunit vaccines

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.

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.

Production of subunit vaccine by recombinant DNA technology.

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.

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.

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?

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.

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

Construction of attenuated viruses by using recombinant DNA technology.