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
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.