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The terms vaccination and vaccine derive from the work of Edward Jenner who, over 200 years ago, showed that inoculating people with material from skin lesions caused by cowpox (L. vaccinus, of cows) protected them from the highly contagious and frequently fatal disease smallpox.
Link to discussion of smallpox. |
Since Jenner's time, the term has been retained for any preparation of dead or weakened pathogens, or their products, that when introduced into the body, stimulates the production of protective antibodies or T cells without causing the disease. In molecular terms, the goal is to introduce harmless antigen(s) with epitopes that are also found on the pathogen.
Vaccination is also called active immunization because the immune system is stimulated to develop its own immunity against the pathogen. Passive immunity, in contrast, results from the injection of antibodies formed by another animal (e.g., horse, human) which provide immediate, but temporary, protection for the recipient. [Link to discussion of passive immunity]
Hepatitis B infection is strongly associated with the development of liver cancer. Here then is the first vaccine against a cancer. |
It has the disadvantage that — on rare occasions — one of the strains in the vaccine regains full virulence and causes the disease. For this reason, the Salk vaccine has once again become the preferred vaccine in the U. S.
Here is a table describing some of the most widely-used vaccines used in humans.
Disease | Preparation | Notes | |
Diphtheria | Toxoid | Often given to children in a single preparation (DTP; the "triple vaccine") or the now-preferred DTaP using acellular pertussis |
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Tetanus | Toxoid | ||
Pertussis | Killed bacteria ("P") or their purified components (acellular pertussis = "aP") | ||
Polio | Inactivated virus |
Inactivated polio vaccine: IPV (Salk) | |
Attenuated virus | Oral polio vaccine; OPV (Sabin) Both vaccines trivalent (types 1, 2, and 3) | ||
Hepatitis A | Inactivated virus | Available as HAVRIX® and VAQTA® | |
Hepatitis B | Protein (HBsAg) from the surface of the virus | Made by recombinant DNA technology | |
Diphtheria, tetanus, pertussis, polio, and hepatitis B | uses acellular pertussis and IPV (Salk) | Pediarix®; combination vaccine given in 3 doses to infants | |
Measles | Attenuated virus | Often given as a mixture (MMR) Do not increase the risk of autism. (Nor do any vaccines containing thimerosal as a preservative.) |
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Mumps | Attenuated virus | ||
Rubella | Attenuated virus | ||
Chickenpox (Varicella) | Attenuated virus | Caused by the varicella-zoster virus (VZV) | |
Influenza | Hemagglutinins | Contains hemagglutinins from the type A and type B viruses recently in circulation [Details] |
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Attenuated virus | FluMist® — contains weakened viruses of the type B and two type A strains recently in circulation |
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Pneumococcal infections | Capsular polysaccharides | A mixture of the capsular polysaccharides of 23 common types. Works poorly in infants. | |
7 capsular polysaccharides conjugated to protein | Mobilizes helper T cells; works well in infants. | ||
Staphylococcal infections | 2 capsular polysaccharides conjugated to protein | To prevent infection by Staph. aureus in patients hospitalized and/or receiving dialysis | |
Meningococcal disease | 4 polysaccharides conjugated to protein | To prevent outbreaks among new groups of young adults, e.g., college freshmen, military recruits | |
Hemophilus influenzae, type b (Hib) | Capsular polysaccharide conjugated to protein | Prevents ear infections in children | |
Hepatitis A | Inactivated virus | Available in single shot with HBsAg (Twinrix®) | |
Rabies | Inactivated virus | Vaccine prepared from human diploid cell cultures (HDCV) has replaced the duck vaccine (DEV) |
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Smallpox | Attenuated virus | Despite the global eradication of smallpox, is used to protect against a possible bioterrorist attack | |
Anthrax | Extract of attenuated bacteria | Primarily for veterinarians and military personnel | |
Typhoid | Three available: 1. killed bacteria 2. live, attenuated bacteria (oral) 3. polysaccharide conjugated to protein |
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Yellow fever | Attenuated virus | ||
Tuberculosis | Attenuated bacteria (BCG) | Rarely used in the U.S. |
The greatest triumph is the eradication of smallpox from the planet, with no naturally-occurring cases having been found since 1977. "Naturally-occurring" because one case (fatal) occurred later following the accidental release of the virus in a laboratory. As far as the public knows, smallpox virus now exists only in laboratories in the U. S. and Russia. There is currently a vigorous debate as to whether these should be destroyed. If smallpox ever should get back out into the environment, the results could be devastating because smallpox vaccination is no longer given and so the population fully susceptible to the disease grows year by year. [More]
A program to try to eliminate polio from the world is now underway. Except for cases caused by OPV, the disease has now been eliminated from the Western hemisphere. Outbreaks of polio still occur in Africa, the Indian subcontinent, and parts of the Near East.
This table compares the number of cases of illness in the U.S. in a representative year (either before a vaccine was available or before it came into widespread use) with the number of cases reported in 1994.
Disease | Total cases | Year | Cases in 1994 | % Change |
---|---|---|---|---|
Diphtheria | 206,939 | 1921 | 2 | -99.9% |
Measles | 894,134 | 1941 | 963 | -99.9% |
Mumps | 152,209 | 1968 | 1537 | -99.9% |
Pertussis | 265,269 | 1934 | 4617 | -99.9% |
Poliomyelitis* | 21,269 | 1952 | 0 | -100% |
Rubella | 57,686 | 1969 | 227 | -99.9% |
Tetanus | 1,560 | 1923 | 51 | -99.9% |
With so many triumphs, why haven't vaccines eliminated other common diseases such as malaria and HIV-1 infection (the cause of AIDS)?
One problem is that experimental vaccines often elicit an immune response that does not actually protect against the disease. Most vaccines preferentially induce the formation of antibodies rather than cell-mediated immunity. This is fine for those diseases caused byBut viruses are intracellular parasites, out of the reach of antibodies while they reside within their target cells. They must be attacked by the cell-mediated branch of the immune system, such as by cytotoxic T lymphocytes (CTLs). Most vaccines do a poor job of eliciting cell-mediated immunity (CMI).
Example:
Much of the early — and so far unsuccessful — work on anti-HIV-1 vaccines has focused on the antibody response of the test animal. Antibodies may have a role in preventing infection or minimizing its spread, but cell-mediated responses will probably turn out to be far more important. Certainly there are thousands of patients dying of AIDS despite their high levels of anti-HIV-1 antibodies. (The most widespread test for HIV-1 infection does not detect the presence of the virus but the presence of antibodies against the virus.)
Discussion of cell-mediated immunity |
How cytotoxic T lymphocytes (CTL) work |
With DNA vaccines, the subject is not injected with the antigen but with DNA encoding the antigen.
The DNA is incorporated in a plasmid containingIn contrast to conventional vaccines, DNA vaccines elicit cell-mediated — as well as antibody-mediated — immune responses.
How antigens are presented to cytotoxic T cells |
Dendritic-cell vaccines in cancer immunotherapy |
Related link: The Immunological Synapse |
So far, most of the work on DNA vaccines has been done in mice where they have proved able to protect them against tuberculosis, SARS, smallpox, and other intracellular pathogens. In addition, more than a dozen different DNA vaccines against HIV-1 — the cause of AIDS — are in clinical trials.
Flu vaccines |
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