Vaccines are a variety of agents used to prevent infection by elevating immunological sensitivity to potential pathogens. Attenuated (significantly less dangerous) versions of infectious agents are used to enhance the natural immune response typically through injection or oral ingestion. Vaccination programs have enjoyed positive and negative reviews, but it is undeniable fact that vaccination programs in some parts of the world have saved thousands of lives.

History of Vaccines

The history of vaccines and vaccination predates modern microbiology significantly.  Shrewd observation of individuals who had survived potentially deadly diseases showed a dramatic reduction in further infections. Although there was little understanding of the microbiological causes of these infectious diseases, it was apparent that prior exposure played a significant role in resisting and surviving infections.

One early process was termed variolation which involved inhaling or injecting material from the scabs or lesions of a recovering individual. This was practiced in China as early as the 1700's.

In England in 1796 Dr. Edward Jenner made full use of information provided by milkmaids - if they had acquired the mild cow pox, they could not acquire the deadly and dreaded small pox.  In an experiment that would likely see him jailed for life in modern times, Dr. Jenner infected a young boy with cow pox. When the boy recovered from the mild infection Dr. Jenner then injected him with small pox. Most fortunately, the boy did not contract any small pox symptoms. Despite apparent and overwhelming evidence (23 additional case histories) the Royal Society of London refused to publish his findings. Dr. Jenner published his findings out of his own pocket and the rest became history.

The single greatest consequence of vaccination programs has been a phenomenal reduction in infection and mortality due to infectious disease. The example below illustrates the impact of the polio vaccine developed by the Canadian scientist Dr. Salk.

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The Immune Response

The purpose of vaccination is quite simple: to acquaint the immune system with the biochemical profile / molecular signature of the infectious agent. Any foreign molecule which can initiate an immune response in a host is termed an antigen. The body's response is to produce antigens which will retain a biochemical memory and remain sensitive to future infections by the same (or similar) agents.

The normal immune response involves a series of cellular and biochemical agents, some of which directly attack invading molecules and cells, others which summon other, more specific cells and molecules to assist in the process. A very simplified overview is provided below:

1. Recognition - T Cells recognize the antigen (likely specific proteins on the surface of the invading molecule). The T Cells also begins to reproduce creating many more cells capable of recognizing and responding to the antigen / virus.
2. Attack -  some T Cells attack the virus / antigen directly, as well as attacking and destroying host cells which are already infected.
3. Reinforcements - some T Cells send chemical signals to stimulate B Cells. The B Cells produce antibodies which locate, bind and hold the antigen with absolute molecular specificity.
4. Agglutination - the antibody-antigen complex begins to form,  locating and immobilizing the invading pathogen. This permits other cells and systems (Killer Cells, Complement System) to respond and eliminate the antigenic molecule / pathogen.

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In addition to recognizing and eliminating the foreign / invading pathogen, the immune system deploys memory cells to ensure a rapid immunological response against future infections by the same (or closely related) pathogens. It is the goal of vaccination to create the memory (and effective immune response) without the clinical consequences of the pathological condition.

Vaccine Production

Vaccine production employs "attenuated" (harmless) versions of pathogenic organisms. This may involve the use of dead pathogenic cells, or alternatively, portions of pathogenic cells which are capable of eliciting an immune response without causing any of the disease symptoms.

Inactivated Vaccines - these vaccines are produced from dead pathogens. One method is to heat-kill the pathogen, another long-standing method for inactivating the pathogen has been to use formalin. Critics of the technique point out that ingestion of even trace levels of formalin is not beneficial. The polio vaccine (Salk) was produced by this method was exceptionally effective at stopping an epidemic of polio which once was a horror for parents and children alike. Since inactivated vaccines involve exposing the pathogen to severe, lethal conditions there can be changes in the antigenicity of the vaccine. This can mean that repeated booster shots are necessary to maintain long term immunity. Examples include:

	Inactivated polio vaccine (IPV)
	Inactivated influenza vaccine

 Acellular / Component Vaccines - this type of vaccine is produced by identifying and then isolating components of the infectious agent that elicit the immune response. Since the infectious agent is only represented by a few characteristic molecules there is an immune response but no risk of infection. As in the case of inactivated vaccines, using only part of a pathogenic agent may result in a somewhat weakened antigenic response and the need for periodic booster shots. Examples include:

	Haemophilus influenzae type b (Hib) vaccine
	Hepatitis B (Hep B) vaccine
	Hepatitis A (Hep A) vaccine
	Pneumoccocal conjugate vaccine

Attenuated Vaccines -  these vaccines are produced by weakening (attenuating) a living pathogen so that it retains all of it's antigenic properties but is no longer capable of causing a pathological condition. Attenuated vaccines are the most effective by far, being employed against conditions such as measles and mumps- typically providing lifelong immunity from a single exposure. There is a risk however, that these attenuated forms could mutate back into their more virulent forms causing the disease they were meant to prevent.  Examples include:

	Measles vaccine (as found in the MMR vaccine)
	Mumps vaccine (MMR vaccine)
	Rubella (German measles) vaccine ( MMR vaccine)
	Oral polio vaccine (OPV)
	Chickenpox vaccine

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Toxoid Vaccines - this type of vaccine is made from toxins produced by a pathogen. The toxin is chemically treated to remove it's negative impact, but this type of vaccine only produces a lower level of immunological protection. Diptheria vaccine is a toxoid. In order to enhance the immune response toxoid vaccines are often given in combinations as conjugated vaccines. Examples include:

	Diphtheria toxoid vaccine
	Tetanus toxoid vaccine

Analogue Vaccines - analogue vaccines employ a "bait-and-switch" technique but using a closely-related, but harmless organisms to confer protection against a significantly more pathogenic organism. This is similar to the technique employed in early China and by Dr. Jenner in the late 1700's in England where cowpox was used to protect against lethal smallpox.

Vaccines through Genetic Engineering

Molecular biology techniques now allow the isolation of key genetic sequences which produce subunit or indicator molecules which can elicit a strong immune response. The concept is to grow large quantities of the indicator subunits by inserting the genetic sequence in an appropriate host.  Production techniques under development have created vaccines from a broad spectrum of host cells: bacteria and yeast, chicken eggs and even plants have been examined as potential producers of significant quantities of engineered vaccines. Typically cell / tissue culture techniques are employed to produce large quantities of antigens from the GM (genetically modified) host cells.

Individual versus "Herd Immunity"

Although the initial benefit of immunization may be to an individual, the real effectiveness of an immunization program is confer "herd immunity". When a disease is able to persist and spread through a population it often mutates and changes with respect to virulence, persistence and infectivity. When an entire population is immunized there is little chance of transmission and greatly reduced odds of mutation. In some cases this can lead to the effective eradication of diseases which were once a deadly threat to mankind. Often the immunization requirements for international travel have less to do with the well-being of the individual and more to do with protecting the general population from new infectious agents.

Negative Aspects of Immunization

All medical procedures involve varying degrees of risk. In the case of polio the consequences of the disease significantly outweigh the risk of vaccination, but this is not always the case. Growing numbers of children appear to have allergenic responses to environmental stimulants and some types of vaccines carry greater risk for immuno-compromised individuals. Sensitivity to formalin (or other components of vaccines) may  negatively impact sensitive individuals. Understanding the risks associated with the presence or absence of vaccines is an important responsibility.