Active immunity is brought about through the stimulation of the immune system to produce antigen-specific humoral (antibody) and cell-mediated immunity.  Active immunity involves the production of memory lymphocytes, in which immunological protection will last for many years, if not for a lifetime.  This effective, memory-based immunity is established after every natural primary infection.  The nature of vaccines is to elicit this beneficial long-term immunity without inducing disease.  To accomplish this feat, two types of viral vaccines have been readily employed:  live attenuated and inactivated.
 
 

Live Attenuated Vaccines

Most of the live attenuated vaccines in use today are derived from serial passage in cultured cells, including human diploid cells (e.g. fetal lung tissue, other fibroblasts), monkey kidney cells, and chick embryos, among others.  Adaptation of the virus to growth in the cultured cells is accompanied by a gradual loss of virulence for the natural host.  The neurovirulence of the attenuated virus is tested in mice and primates before conducting trials with humans.  This procedure relies on the accumulation of point mutations to confer avirulence; however, more exact mutations can be attained through genetic engineering.  Temperature sensitive mutants, deletion mutants, site-directed mutatgenesis, and live recombinant viruses are all methods that are commonly employed to achieve viral attenuation.  These vaccines generally possess the following properties:

  • derived from wild virus
  • attenuated through repeated culturing or recombination
  • must replicate to be effective
  • produces strong cellular immune response similar to natural infection
  • severe reactions possible in immunosuppressed vaccinees
  • can revert to pathogenic form
  • require only one or two doses
  • interference from circulating antibody
  • require refrigeration or lyophilization (freeze-dry)
  • unstable

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    Inactivated Vaccines

    Inactivated viruses are also propagated on a cell culture line, but they are killed with the use of an inactivating agent such as formalin, B-propiolactone, and ehtylenimines.  The overall goal is to destroying the infectivity of the virus, while maintaining its immunogenicity.  The overall disadvantage is that the use of these "weaker" vaccines necessitates multiple booster shots.  In cases where the inactivated virion can still produce a febrile response or a local reaction, purified protein vaccines are used instead.  All the nonessential components of the virion are removed (with the help of ether and detergents), and only the relevant immunogenic surface proteins are administered, inducing the production of neutralizing antibodies to specific epitopes.  Other procedures involve cloning the appropriate genes into prokaryotic cells (e.g. bacteria, yeast), leading to the production of the immunogenic proteins.  Characteristics of inactivated viral vaccines include:

  • can be whole or fractional virion
  • grown in culture and inactivated with heat or chemicals (e.g. formalin)
  • cannot replicate
  • minimal interference from circulating antibody
  • require multiple doses
  • immune response mostly humoral and short-lived
  • costlier than live attenuated version
  • may require adjuvant to help stimulate immunity
  • not as toxic
  • safer especially if virus is higly virulent

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    Additives

    Once the viruses have been propogated on the cell culture line, they undergo a purification process involving cell lysis, ultrafiltration, centrifugation, sucrose density gradients, suspensions, and exclusion gel chromatography among many extraction procedures.  In the case of inactivated vaccines, formalin (or any other inactivating compound) and an adjuvant (often aluminum hydroxide) are added.  Vaccines tend to contain several additives including the following::

  • Suspending fluids of sterile water or saline
  • Antibiotics such as neomycin to prevent the growth of bacteria
  • Aluminum salts to initiate antibody responses
  • Formalin to inactivate viruses and bacteria
  • Monosodium glutamate as a stabilizer
  • Egg protein from viruses cultured in embryonated chicken eggs
  • Sulfites as preservatives
  • Thimerosal to prevent spoilage

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    Administration of Vaccines

    Recommendations for the administration of vaccines in the United States are determined by public health officials associated with health organizations such as the Immunization Practices Advisory Committee (ACIP), the American Academy of Family Physicians (AAFP), the National Vaccine Advisory Committee, and the American Academy of Pediatrics (AAP).  They determine the appropriate vaccines, ages, doses, and time schedules for immunization based on theoretical considerations, experimental trials, and clinical experience.
    Depending on the formulation, viral vaccines are administered through three routes:

  • Oral administration
  • Subcutaneous injections are administered in the thigh of infants or in the deltoid area of adults
  • Intramuscular injections are generally applied to a large muscle group, either the anterolateral aspect of the upper thigh in infants and the deltoid muscle of the upper arm for adults.

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    Side Effects

    The majority of side effects are limited to local reactions at the site of injection:  redness, swelling, or itching.  Allergic responses (anaphylaxis) can range from mild manifestations to more  severe complications such as hives, swelling of the mouth and throat, difficulty breathing, hypotension, or shock.  These infrequent anaphylactic reactions are due to overactive immunological responses to vaccine components such as animal protein, antibiotics, preservatives, and stabilizers.  Generally, inactive vaccines are more tolerated than live, attenuated vaccines that may elicit febrile conditions, particularly in children.  Live vaccines can potentially revert to more virulent forms, leading to the manifestation of disease on rare occasions; immunosuppressed individuals are not to receive live, attenuated vaccinations.  Largely in response to the reported cases of vaccine-associated paralytic polio, the National Vaccine Injury Compensation Program (VICP) was established by the National Childhood Vaccine Injury Act of 1986.  The program requires physicians and other health-care providers who administer vaccines to maintain permanent immunization records and to report occurrences of certain adverse events to the U.S. Department of Health and Human Services.  Information regarding reportable side effects, compensation, and the procedures for filing a claim can be found on the VICP webpage.
     
     
     

    Vaccine Suppliers

    Several pharmaceutical companies are responsible for supplying the currently licensed vaccines.  Among many suppliers, they include:


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