Vaccines

Active Immunization or Vaccination

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.

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.

Kinds of Vaccines

1. Killed whole organisms

In this relatively crude approach, the vaccine is made from the entire organism, killed to make it harmless. The typhoid vaccine is an example.

2. Attenuated organisms

Here, the organism has been cultured so as to reduce its pathogenicity, but still retain some of the antigens of the virulent form. The Bacillus Calmette-Guérin (BCG) is a weakened version of the bacterium that causes tuberculosis in cows. BCG is used as a vaccine against tuberculosis in many European countries but is rarely used in the U. S.

3. Toxoids

In some diseases, diphtheria and tetanus are notorious examples, it is not the growth of the bacterium that is dangerous, but the protein toxin that is liberated by it. Treating the toxin with, for example, formaldehyde, denatures the protein so that it is no longer dangerous, but retains some epitopes on the molecule that will elicit protective antibodies.

4. Surface molecules

Antibodies are most likely to be protective if they bind to the surface of the invading pathogen triggering its destruction. Several vaccines employ purified surface molecules:

5. Inactivated virus

Like killed bacterial vaccines, these vaccines contain whole virus particles that have been treated (again, often with formaldehyde) so that they cannot infect the host's cells but still retain some unaltered epitopes. The Salk vaccine for polio (IPV) is an example.

6. Attenuated virus

In these vaccines, the virus can still infect but has been so weakened that it is no longer dangerous. The measles, mumps, and rubella ("German measles") vaccines are examples. The Sabin oral polio vaccine (OPV) is another example. It has advantages over the Salk vaccine in that

It has the disadvantage of - on rare occasions - regaining full virulence and causing 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
Tetanus Toxoid
Pertussis Killed bacteria ("P") or their purified components (acellular pertussis = "aP")
Polio Inactivated virus
Inactivated polio vaccine: IPV (Salk)
Attenuated virusOral polio vaccine; OPV (Sabin)
Both vaccines trivalent (types 1, 2, and 3)
Measles Attenuated virus Often given as a mixture (MMR)
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]
Pneumococcal pneumonia Capsular polysaccharides A mixture of the capsular polysaccharides of 23 common types
Meningococcal disease Polysaccharides Used chiefly to prevent outbreaks among the military
Hemophilus influenzae, type b (Hib) 4 polysaccharides Prevents ear infections in children
Hepatitis B Protein (HBsAg) from the surface of the virus Made by recombinant DNA technology
Rabies Inactivated virus Vaccine prepared from human diploid cell cultures (HDCV)
has replaced the duck vaccine (DEV)
Rotavirus (causes severe diarrhea in children) Attenuated virus (RRV-TV) Because of a few reports of severe side-effects, should not be used until further notice (expected November 1999).
Smallpox Attenuated virus No longer used since smallpox has been eradicated throughout the world
Typhoid Killed bacteria  
Yellow fever Attenuated virus  
Tuberculosis Attenuated bacteria (BCG) Rarely used in the U.S.

Some of the Triumphs of Vaccination

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.

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.

DiseaseTotal casesYearCases in 1994% Change
Diphtheria206,93919212-99.9%
Measles894,1341941963-99.9%
Mumps152,20919681537-99.9%
Pertussis265,26919344617-99.9%
Poliomyelitis*21,26919520-100%
Rubella57,6861969227-99.9%
Tetanus1,560192351-99.9%
*Since 1979, an average of 8 cases of poliomyelitis have occurred in the U.S. each year that are acquired from the vaccine (OPV, the Sabin vaccine) itself. For this reason, the "killed" virus vaccine (IPV, the Salk vaccine) is being reintroduced. As of June 17, 1999, it is recommended that in the future all children receive 4 doses of the Salk vaccine and - except in special circumstances - none of the Sabin vaccine.

Problems of vaccine development

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 by

But 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-mediate 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

DNA Vaccines?

With DNA vaccines, the subject is not injected with the antigen but with DNA encoding the (protein) antigen. The DNA is incorporated in a plasmid, which is then injected into a muscle just as conventional vaccines are.

How antigens are presented to cytotoxic T cells

So far, most of the work on DNA vaccines has been done in mice where they have proved to protect them against tuberculosis and other intracellular pathogens. Some experimental work has even been done in humans using a DNA vaccine encoding one of the surface antigens of Plasmodium falciparum, the cause of one of the most serious forms of malaria.

Flu vaccines
Welcome&Next Search

27 July 1999