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Vaccination protects a person from
becoming infected with bacteria or viruses by stimulating the body's immune system to produce antibodies (blood proteins) that, in most cases,
protect against infection. In order to accomplish this, vaccines against specific infections need to “trick” the immune system into responding to the vaccine in the same way as
it would the infection but without causing an illness.
A vaccine should not cause the disease it is designed to prevent and should be free of harmful side effects.
This is accomplished in a variety of different ways:
Inactivating the part of bacteria (toxin) causing the disease. Each toxin is a protein, and for some bacteria
such as diptheria, tetanus and pertussis these toxins are chemically inactivated. The resulting weakened toxins or toxoids
are used in making diptheria, tetanus and pertussis vaccines.
Using part of the bacteria, the polysaccharide (sugar) coat, to trick the immune system into making antibodies that protect against the whole bacteria.
Examples of this type of vaccine are the pneumococcal or meningococcal polysaccharide vaccines. To strengthen the immune response even further, especially in
children younger than 2 years of age who do not respond well to vaccines made of bacterial polysaccharides alone, some vaccines link the bacterial polysaccharide to a harmless protein in a process called conjugation. The resulting conjugated polysaccharide vaccines (for example, Haemophilus influenzae type B conjugate, meningococcal conjugate and pneumococcal conjugate) give more long-lasting immunity and prompt a better response in young children.
Using live but weakened (attenuated) virus that reproduces in very small quantities in the body. The quantity of the virus in the body is adequate to trick the immune system into responding to the vaccine but is not so large as to cause the disease to develop. However, these live viral vaccines can not be given to people with certain immune system disorders who would be at risk of developing the disease even with exposure to small amounts of virus (for example, people with HIV infection
or certain types of cancer or who take certain drugs that affect
the immune system). Examples of live viral vaccines include measles, mumps, rubella (MMR), varicella and live, attenuated influenza (LAIV) vaccines.
Inactivating the virus chemically so that it will not reproduce in the body.
However, even though the virus is not active, the immune system
produces antibodies in response to the presence of killed virus.
This type of viral vaccine usually requires a number of doses in
order to stimulate a sufficient immune response. Examples of
this type of vaccine are inactivated polio, hepatitis A, trivalent inactivated influenza (TIV) and rabies vaccines.
Using part of a virus to stimulate the immune system.
Vaccines made in this way are hepatitis B vaccine and the HPV vaccine.
Vaccine research and development
Vaccine research and development (R&D)
involves many phases of testing to ensure efficiency and safety.
Typically, it takes 20 or more years from initial
research—including many phases of testing potential vaccine
candidates— to arrive at vaccine licensure. This lengthy process
involves biotechnology companies and vaccine manufacturers, as well as other partners including the United States government.
Partners in vaccine R&D include
the following groups:
The
National Institutes of Health (NIH) is the major source of funds for research largely through academic programs into basic scientific principles and vaccine concepts. It also has a role in clinical development within the United States through its Vaccine Trial Evaluation Units. The
Food and Drug Administration Agency (FDA) is responsible for licensing new pharmaceutical products including vaccines. It establishes standards for manufacturing processes and reviews pre- and post-licensure studies to ensure vaccines are safe and effective. It also has an
internal research base to evaluate data efficiently. The
Centers for Disease Control and Prevention (CDC) is responsible for epidemiological and surveillance studies that define risk factors for disease, disease burden and the likely public health impact of a particular vaccine. It also recommends how vaccines
should be used and administered through the work of its
Advisory Committee on Immunization Practices (ACIP). It is responsible for the public purchase of vaccines (more
than 50 percent of all childhood vaccines) and so is a determinant of vaccine demand and profit. The
U.S. Agency for International Development (USAID) supports targeted R&D on vaccines likely to have the most effect on children
younger than 5 years in developing countries. The
U.S. Department of Defense (DOD) supports targeted research on vaccines likely to protect the military against infections prior to their serving abroad Nongovernmental organizations, such as the
Bill and Melinda Gates Foundation, provide increasing funding for vaccine research to target diseases in the developing world Academic institutions are involved in scientific research, the development of and in performing clinical trials of candidate vaccines
Vaccine licensure and introduction into the
immunization schedule
The first step in licensure is the submission of an Investigational New Drug (IND) application to the FDA. This application includes information on the vaccine's safety and ability to elicit an immune response (immunogenicity) when tested in the laboratory and on animals. It also describes how the vaccine is manufactured and the quality control processes. It provides a proposed clinical protocol for performing pre-licensure (Phase, 1, 2 and 3) studies. Phase 1 human studies of the vaccine are performed after the IND application has been reviewed and approved by the FDA. These are studies of the safety and immunogenicity in a small number (typically
less than 100) of healthy, human volunteers who are very closely monitored for any adverse events. If the results of these studies demonstrate acceptable safety and immunogenicity, further studies are performed. Phase 2 studies build on the information gathered from Phase 1 studies. They are carried out in hundreds of people, typically people who will be candidates for the vaccine when it is licensed. Phase 2 studies evaluate the safety and immunogenicity of a vaccine when administered in different doses. If the results of these studies are acceptable, the vaccine is further developed. Phase 3 studies enroll thousands of subjects and evaluate vaccine safety and immunogenicity as well as demonstrating if a vaccine is effective. At each stage of the pre-licensure studies, study results are reviewed by independent experts to ensure vaccine safety and effectiveness. If concerns are raised at any stage, clinical trials may be halted. The FDA may also request and require further studies or information on the vaccine at any time. Following successful completion of the pre-licensure studies, a Biologics License Application (BLA) can be submitted to the FDA. This application must be reviewed and approved by a multi-disciplinary FDA reviewer team. The manufacturing facility also undergoes a pre-approval inspection at this time. The manufacturer and FDA next present their findings to the FDA's Vaccine and Related Biological Products Advisory Committee (VRBPAC). This independent expert committee reviews all the available data and advises the FDA regarding the safety and efficacy of the vaccine for its' proposed use. After a vaccine is licensed by the FDA, the FDA continues to oversee the vaccine production and periodically inspect the production facilities. Manufacturers also may be required to submit samples of vaccine to the FDA for testing After a vaccine is licensed by the FDA, the results of all studies are reviewed by the ACIP of the CDC. This group of vaccine experts then issues recommendations on whether, how and in whom a vaccine should be used. CDC, and other professional organizations such as the
American Academy of Pediatrics (AAP) and
American Academy of Family Physicians (AAFP), then make final written recommendations. Phase 4 post-licensure studies are performed after a vaccine has been licensed and introduced into the immunization schedule. The CDC continually monitors vaccine safety. Phase 4 studies are designed to detect uncommon and rare side effects that may not have been detected in the pre-licensure stage. The CDC accomplishes this by monitoring disease reports to each health department nationwide and seeing if any unusual occurrences may be vaccine related. The CDC has also set up vaccine surveillance systems such as Vaccine Adverse Event
Reporting System (VAERS) and Vaccine Safety Datalink (VSD) to detect potential adverse events in a timely manner. These systems demonstrated their worth in the late 1990s through detecting that a previously available rotavirus vaccine rarely caused intussusception (a bowel complaint). This led to the vaccines withdrawal from the market and the subsequent development and licensure of a new rotavirus vaccine that was tested for this and other complications before it was licensed and recommended.
 
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