Vaccines and Immunotherapies

5 Jun

INTRODUCTION

Patients are  inoculated with one of two intents: prevention of a disease through the immune response (vaccination) and  pro- phylaxis to protect those already exposed to a disease and  for whom  regular vaccination would  not  be effective. If humans could control virus transmittal in nonhuman reservoirs, elim- inate vectors, and  improve sanitation, then vaccines and  other immunomodulators would  be  less  necessary. Instead, many human activities may  promote opportunities for virus trans- mittal and  improper sanitation, particularly in  third-world countries when new agricultural crops  or production methods are  introduced; populations become  concentrated in  an  area with new  economic development and  no sanitary infrastruc- ture; or  in  populations that move  into  vector  habitats that were  previously undisturbed. Nonhuman animal reservoirs can be controlled through vaccination, removal of stray or wild animals, and   quarantine. Vector   control usually involves draining swamps, spraying insecticides, using insect repellent

and  long-sleeved or -legged  clothes, screening, etc. Improving sanitation involves breaking the  fecal-oral transmission cycle, which includes drinking water chlorination and  proper treat- ment of wastewater. The  use  of vaccines is only one aspect of controlling the  spread of viruses and  should be  used along with other public  health measures.

The global eradication of poliomyelitis is currently under- way, with an unmet target goal of 2000 (1). A number of other virus vaccines have led to notable decreases in infections and complications. In 2002,  an  all-time low of 37 cases of measles was  recorded in the  United States. Worldwide eradication for measles is  targeted for  2005–2010. Currently  available vac- cines  provide a basic  framework of knowledge and  experience with which other virus vaccines can  be developed. The  inci- dence  of many viral infections, such  as herpes simplex viruses, human papillomaviruses, and  HIV, as well as newly  emerging viruses, such  as  Ebola and  West  Nile  viruses, means that no let up in vaccine development is in sight (Fig. 4.1).

By administering antibodies from  another host, usually in an antibody-containing gamma globulin preparation, into  a sus- ceptible individual, some form of temporary immunity either pro- tects the individual from getting the disease or reduces the effects of the  disease. Active  prophylaxis, delivered as a vaccine, stimu- lates an  antibody response via T lymphocytes. The  vaccine effi- cacy is measured in the  length of immunity (over time) and  the proportion of persons vaccinated who  demonstrate immunity. While  immunity diminishes over  time, recent studies indicate

Fig. 4.1     Occurrence of Emerging Viral Diseases and Vaccine Development (1950–2003). Vaccines with the  most  impact are those designed to eradicate viral diseases of childhood. For  some diseases, vaccines are  available but  are  not  routinely administered to anyone other than animal care  workers, foresters, or health-care workers due  to limited availability, adverse events, or incidental exposure. A 100% vaccination rate is usually not  achieved. Some diseases, such  as  yellow  fever, depend upon  vector  control and have reemerged as  agricultural practices and  vector-control policy have changed. In summary, progress is being  made, but  the  viruses are  emerging faster than they are  being  eradicated or controlled.

that those vaccinated against smallpox over  30 years ago  con- tinue to demonstrate some  level  of immunity to the  smallpox virus. Many vaccines have been developed since the original cow- pox (smallpox) vaccine in  1796.  As viruses have become  more prominent and  vaccine technology has  changed, vaccines of vari- ous etiologies are  being  approved on a regular basis (Table 4.1).

Currently,  vaccines are   derived from  three different mechanisms:

Attenuated live viral vaccine. A live vaccine contain- ing a virus that has been manipulated in the laboratory. These special viruses can  infect and  replicate in  the vaccine to produce an  immune response without caus- ing  illness. There is always the  danger that the  virus will  mutate to  a  more  pathogenic form.  Fortunately, current in vitro, in vivo, and  clinical tests must assess and  report this risk before  the  vaccine is licensed for use  in the  general population. New  recombinant  DNA strains have had  genetic regions deleted that are  most likely   to  mutate to  pathogenic strains. Most  of the vaccines developed prior to 1960  were  attenuated live vaccines. Varicella, yellow fever, measles, mumps, rubella,

oral  polio  vaccine, and  some  adenovirus vaccines are examples of attenuated live viral vaccines.

Killed viral vaccines (inactivated). Whole virus parti- cles or some component of the  virus, either of which has been  deactivated chemically or  physically. These vac- cines  do not  cause infection but  stimulate an  immune reaction. Usually, repeated doses  are  required as  one dose  does  not  confer  lifelong immunity. Large quanti- ties  of viral antigens per  dose are  necessary to produce an adequate response. Influenza, Salk polio, rabies, and Japanese encephalitis vaccines are  of this type.

Recombinant antigens. Tend  to  be newer versions of earlier vaccines and  furnish better protection with less risk and fewer side effects. Specific components that elicit production of protective antibodies are  cloned.  These express the  gene  that encodes that protein or protein complex. The  new  hepatitis B vaccine is this type.

The  different types of vaccines that  produce immune responses in  a variety of cell  types are  shown in Table 4.2. Vaccine-induced immunity is a relative science. Selecting the correct dosage(s), timing of dosages, and  determining the long- term efficacy  are  trials facing  vaccine development. Normally, B cells,  CD8+ T cells  and  CD4+ T cells  mediate immune func- tions. B-cell functions may  involve  secretion of IgG antibodies or  secretory IgA  antibodies.  CD4+  and  CD8+  T cells  provide support for B cells  and  CD8+  T cells  assist in  killing human leukocyte antigen (HLA)-matched infected cells. B cells, when mediated by T-helper cells, are  thought to provide long-lasting immunity despite negative antibody test results (2).

Table 4.2 Roles  of Different Cell Types  in Vaccine-Induced

Immune System Development

B-cells

Live-attenuated virus vaccines, inactivated virus vaccines, protein antigens, capsular polysaccharides with or without carrier.

CD8+   T cells

Live-attenuated virus vaccines.

CD4+   T cells

Live-attenuated virus vaccines, inactivated virus vaccines, protein antigens, and capsular polysaccharides only with a protein carrier.

The development of vaccines may take decades to charac- terize, develop genetic-splicing methods to improve safety and efficacy,  and  complete appropriate  testing. Still, even  after vaccines are  developed, many persons choose  for a variety of reasons not to be vaccinated. Therefore antivirals, prophylaxis therapies, vaccines, and  other immunomodulators all  have a role to play  in disease eradication and  cure.

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