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VACCINE
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CONTENTS
1. Introduction
2. How vaccines work
3. Different types of vaccines
4. Harmful Microbes
5. Vaccine preventable disease and vaccination
6. Vaccine benefits
7. Production
8. Vaccines of the Future
9. Making a safe vaccines
10. FDA License
11. NIAD Vaccine Research
12. Follow-up surveillance
13. Conclusion
14. References
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INTRODUCTION
Vaccines are crucial to maintaining public health: They are a safe, cost-effective, and
efficient way to prevent sickness and death from infectious diseases. Vaccines have led to some
of the greatest public health triumphs ever, including the eradication of naturally occurring
smallpox from the globe and the near eradication of polio.
This booklet contains general information about vaccines
• What they are
• How they prevent disease
•
How they are made and tested
• What vaccine research might achieve in the future
WHAT IS VACCINE
A vaccine is a biological preparation that improves immunity to a particular disease. A
vaccine typically contains an agent that resembles a disease-causing microorganism, and is often
made from weakened or killed forms of the microbe, its toxins or one of its surface proteins.
Chances are never had diphtheria. probably don’t know anyone who has suffered from
this disease, either. Similarly, diseases like whooping cough (pertussis), measles, mumps, and
German measles (rubella) may be unfamiliar to. In the 19th and early 20th centuries, these
illnesses struck hundreds of thousands of people in the United States each year, mostly children,
and tens of thousands of people died.
Chances are the vaccinated against diphtheria. The even may have been exposed to the
bacterium that causes it, but the vaccine prepared body to fight off the disease so quickly that
were unaware of the infection. The body often gains the upper hand after a few weeks, but in the
meantime are sick. Traditional vaccines contain either parts of microbes or whole microbes that
have been killed or weakened so that they don’t cause disease.
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HOW VACCINES WORK
Vaccines do not guarantee complete protection from a disease. Sometimes, this is because the
host's immune system simply does not respond adequately or at all. This may be due to a lowered
immunity in general (diabetes, steroid use, HIV infection, age) or because the host's immune system
does not have a B cell capable of generating antibodies to that antigen. The vaccines are mainly in
newly disease about yellow fever.
ANTIGENS SOUND THE ALARM
The macrophages digest most parts of the yellow fever viruses but save the antigens and
carry them back to the immune system’s base camps, also known as lymph nodes. Lymph
nodes, bean-sized organs scattered throughout body, are where immune system cells congregate.In these nodes, macrophages sound the alarm by “regurgitating” the antigens, displaying them
on their surfaces so other cells can recognize them. In this particular case, the macrophages will
show the yellow fever antigens to specialized defensive white blood cells called lymphocytes,
spurring them to swing into action.
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LYMPHOCYTES: T CELLS AND B CELLS
There are two major kinds of lymphocytes, T cells and B cells, and they do their own
jobs in fighting off yellow fever. T cells and B cells head up the two main divisions of the
immune system army.
T Cells
T cells function either offensively or defensively. The offensive T cells don’t attack the virus but
they use chemical weapons to eliminate the cells of body already infecte directly with the yellow fever
virus. Because they have been ―programmed‖ by their exposure to the virus antigen, these cytotoxic T
cells, also called killer T cells, can ―sense‖ diseased cells that are harboring the yellow fever virus. The
defensive T cells, also called helper T cells, defend the body by secreting chemical signals that direct the
activity of other immune system cells. The work done by T cells is called cellular or cell-mediated
immune response.
B Cells
B cells are like weapons factories. They make and secrete extremely important molecular
weapons called antibodies. Antibodies usually work by first grabbing onto the microbe’s
antigen, and then sticking to and coating the microbe.
Each antibody can usually fit with only one antigen. So immune system keeps a supply
of millions and possibly billions of different antibodies on hand to be prepared for any foreign
invader. immune system does this by constantly creating millions of new B cells. About 50
million B cells circulate in each teaspoonful of blood and almost every B cell — through randomgenetic shuffling produce a unique antibody that it displays on its surface.When these B cells
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came into contact with their matching yellow fever antigen, they were stimulated to divide into
many larger cells called plasma cells that secreted mass quantities of antibodies to yellow fever
virus.
ANTIBODIES IN ACTION
The antibodies secreted by B cells circulate throughout body until they run into the
yellow fever virus. Antibodies attack the viruses that have not yet infected any cells but are
lurking in the blood or the spaces between cells. Antibodies also signal macrophages and other
defensive cells to come eat the microbe. Antibodies are like big, bright
signs stuck to a microbe saying, “Hey, get rid of this!”
The work of B cells is called the humoral immune response, or
simply the antibody response. The goal of most vaccines is to stimulate
this response. In fact, many infectious microbes can be defeated byantibodies alone, without any help from killer Tcells
CLEARING THE INFECTION:
Memory Cells and Natural Immunity
While immune system works to rid body of yellow fever, feel awful. lie in bed, too dizzyand weak even to sit up. During the next several days, skin becomes yellow (or jaundiced) and
covered with purple spots. The vomit blood. After about a week, immune system gains the upper
hand. T cells and antibodies begin to eliminate the virus faster than it can
reproduce. Gradually, the virus disappears from body, and feels better.
get out of bed. Eventually, go back to working the docks.
If are ever bitten by another mosquito carrying the yellow fever virus,
won’t get the disease again. won’t even feel slightly sick. have become
immune to yellow fever because of another kind of immune system cell:
memory cells. After body eliminated the disease, some of yellow-fever-fighting B cells and T
cells converted into memory cells. Memory B cells can quickly divide into plasma cells and
make more yellow fever antibody if needed. Memory T cells can divide and grow into a yellow-
fever-fighting army. If that virus shows up in body again, immune system will act swiftly to
stop the infection.
HOW VACCINES MIMIC INFECTION
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Vaccines teach immune system by mimicking a natural infection. To show how, let’s
jump ahead to the 21st century. Yellow fever is no longer a problem in the United States, but are
a relief worker stationed in a part of the world where the disease still occurs, and the Centers for
Disease Control and Prevention (CDC) recommends vaccination prior to departure.
The yellow fever vaccine, first widely used in 1938, contains a weakened form of the
virus that doesn’t cause disease or reproduce very well. This vaccine is injected into arm.
macrophages can’t tell that the vaccine viruses are duds, so they gobble up the viruses as if they
were dangerous, and in the lymph nodes, the macrophages present yellow fever antigen to T
cells and B cells. The alarm is sounded, and immune system swings into action. Yellow-fever-
specific T cells rush out to meet the foe. B cells secrete yellow fever antibodies. The weakened
viruses in the vaccine can’t put up much of a fight. The mock infection is cleared, and are left
with a supply of memory T and B cells to protect against yellow fever, should a mosquito
carrying the virus ever bite . Next, we’ll take a closer look at different types of vaccines— not allof them employ killed or weakened microbes — and learn how each type works.
DIFFERENT TYPES OF VACCINES
The infectious agent jumps easily from person to person through the air, and it attacks the
lungs, causing terrible coughing, fever, pneumonia, and sometimes paralysis of the respiratory
system. Scientists quickly determine that disease X is caused by a new species of toxic
bacterium. They call it ―bacterium X.‖ Unfortunately, bacterium X is difficult to fight because it
resists most antibiotics, the kind of drug used to treat bacterial infections.
They would figure out what nutrients it requires. They would examine how it damages lung
tissue. Geneticists would analyze bacterium X’s genes. Immunologists would explore how the
immune system responds to bacterium X and why the body sometimes fails to fight off this
microbe. They would identify antigens from X that best stimulate the immune system.
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LIVE, ATTENUATED VACCINES
Some scientists might explore the possibility of developing a live, attenuated vaccine
against X. These vaccines contain a version of the living microbe that has been weakened in the
lab so it can’t cause disease. This weakening of the organism is called attenuation. They elicit
strong cellular and antibody responses, and often confer lifelong immunity with only one or two
doses.
Despite the advantages of live, attenuated vaccines, there are some downsides. It is the
nature of living things to change, or mutate, and the organisms used in live, attenuated vaccines
are no different. If the X vaccine needs to be shipped overseas and stored by health care workers in
developing countries that lack widespread refrigeration, a live vaccine may not be the best choice.
Live, attenuated vaccines are relatively easy to create for certain
viruses. Vaccines against measles, mumps, and chickenpox, for
example, are made by this method. Viruses are simple microbes
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containing a small number of genes, and scientists can therefore more readily control their
characteristics. Viruses often are attenuated through a method of growing generations of them in
cells in which they do not reproduce very well. Live, attenuated vaccines are more difficult to
create for bacteria. Bacteria have thousands of genes and thus are much harder to control.
Scientists working on a live vaccine for bacterium X, however, might be able to use
recombinant DNA technology to remove several key genes from X.
INACTIVATED VACCINES
An inactivated vaccine, or killed vaccine, might be better for bacterium X. Scientists
produce inactivated vaccines by killing the disease-causing microbe with chemicals, heat, or
radiation. Such vaccines are more stable and safer than live
vaccines: The dead microbes can’t mutate back to their disease-
causing state. Inactivated vaccines usually don’t require
refrigeration, and they can be easily stored and transported in a
freeze-dried form, which makes them accessible to people in
developing countries. Most inactivated vaccines, however,
stimulate a weaker immune system response than do live
vaccines. So it would likely take several additional doses, or
booster shots, to maintain a person’s immunity to bacterium X.
SUBUNIT VACCINES
Scientists would certainly look into the possibility of a subunit vaccine for X. Instead of
the entire microbe, subunit vaccines include only the antigens that best stimulate the immune
system. In some cases, these vaccines use epitopes — the very
specific parts of the antigen that antibodies or T cells recognize
and bind to. Because subunit vaccines contain only the
essential antigens and not all the other molecules that make upthe microbe, the chances of adverse reactions to the vaccine are
lower. Subunit vaccines can contain anywhere from 1 to 20 or
more antigens.
They also could manufacture the antigen molecules
from X using recombinant DNA technology. Vaccines produced this way are called
recombinant subunit vaccines. Such a vaccine has been made for the hepatitis B virus.
Scientists inserted hepatitis B genes that code for important antigens into common baker’s yeast.
Research is also continuing on a recombinant subunit vaccine against hepatitis C virus.
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TOXOID VACCINES
Because our imaginary bacterium X secretes a toxin, or harmful chemical, a toxoid
vaccine might work against it. These vaccines are used when a bacterial toxin is the main cause
of illness. Scientists have found they can inactivate toxins by treating them with formalin, a
solution of formaldehyde and sterilized water. Such ―detoxified‖
toxins, called toxoids, are safe for use in vaccines.
When the immune system receives a vaccine containing a
harmless toxoid, it learns how to fight off the natural toxin. The
immune system produces antibodies that lock onto and block the
toxin. Vaccines against diphtheria and tetanus are examples of
toxoid vaccines.
CONJUGATE VACCINES
If bacterium X possessed an outer coating of sugar molecules called polysaccharides, as
many harmful bacteria do, researchers would try making a conjugate vaccine for X.
Polysaccharide coatings disguise a bacterium’s antigens so that the immature immune systems of
infants and nger children can’t recognize or respond to them. Conjugate vaccines, a special type
of subunit vaccine, get around this problem. When making a conjugate vaccine, scientists link
antigens or toxoids from a microbe that an infant’s immune system can
recognize to the polysaccharides. The linkage helps the immature
immune system react to polysaccharide coatings and defend against the
disease-causing bacterium. The vaccine that protects against Hib is a
conjugate vaccine.
DNA VACCINES
Once the genes from bacterium X had been analyzed, scientists could attempt to create a
DNA vaccine against it. Still in the experimental stages, these vaccines show great promise, and
several types are being tested in humans. DNA vaccines take immunization to a new
technological level. These vaccines dispense with both the whole organism and its parts and get
right down to the essentials: the microbe’s genetic material. In particular, DNA vaccines use the
genes that code for those all-important antigens.
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Researchers have found that when the genes for a microbe’s antigens are introduced into
the body, some cells will take up that DNA. The DNA then instructs those cells to make the
antigen molecules. The cells secrete the antigens and display them on their surfaces. In other
words, the body’s own cells become vaccine-making factories, creating the antigens necessary to
stimulate the immune system. A DNA vaccine against X would evoke a strong antibody
response to the free-floating X antigen secreted by cells, and the vaccine also would stimulate a
strong cellular response against the X antigens displayed on cell surfaces. The DNA vaccine
couldn’t cause the disease because it wouldn’t contain bacterium X, just copies of a few of its
genes. In addition, DNA vaccines are relatively easy and inexpensive to design and produce. So-
called naked DNA vaccines consist of DNA that is administered directly into the body. These
vaccines can be administered with a needle and syringe or with a needle-less device that uses
high-pressure gas to shoot microscopic gold particles coated with DNA
directly into cells. Sometimes, the DNA is mixed with molecules that
facilitate its uptake by the body’s cells. Naked vaccines being tested in
humans include those against the viruses that cause influenza and HIV.
RECOMBINANT VECTOR VACCINES
Recombinant vector vaccines could be another possible strategy against bacterium X.
These experimental vaccines are similar to DNA vaccines, but they use an attenuated virus or
bacterium to introduce microbial DNA to cells of the body. Vector
refers to the virus or bacterium used as the carrier. In nature,
viruses latch on to cells and inject their genetic material into them.
In the lab, scientists have taken advantage of this process. They
have figured out how to take the roomy genomes of certain
harmless or attenuated viruses and insert portions of the genetic
material from other microbes into them.
The carrier viruses then ferry that microbial DNA to cells. Recombinant vector vaccines
closely mimic a natural infection and therefore do a good job of stimulating the immune system.
Attenuated bacteria also can be used as vectors. In this case, the inserted genetic material causes the
bacteria to display the antigens of other microbes on its surface. In effect, the harmless bacterium mimics
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a harmful microbe, provoking an immune response. Researchers are working on both bacterial and
viral-based recombinant vector vaccines for HIV, rabies, and measles .
SOME VACCINE TYPES AND DISEASES THEY PROTECT
AGAINST
Vaccine Type Disease
Live, attenuated
vaccines
Measles, mumps, rubella,
polio (Sabin vaccine), yellow
fever
Inactivated or ―killed‖
vaccines
Cholera, flu, hepatitis A,
Japanese encephalitis, plague,
polio (Salk vaccine), rabies
Toxoid vaccine
Diphtheria, tetanus
Subunit vaccines
Hepatitis B, pertussis,
pneumonia caused by
Streptococcus pneumonia
Conjugate
vaccines
Haemophilus influenzae type
b, pneumonia caused by
Streptococcus pneumoniae
DNA vaccinesIn clinical testing
Recombinant
vector vaccines
In clinical testing
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HARMFUL MICROBES
Vaccines protect against infectious diseases caused by microbes — organisms too small
to see without a microscope. Many microbes, such as bacteria, are made up of only one cell.
Viruses, mere snippets of genetic material packed inside a membrane or a protein shell, are
even smaller. Humans evolved an immune system because the world is teeming with these
organisms. Many of them don’t bother us; the bacteria that normally live in digestive tract are,
in fact, beneficial. But other microbes break into and take up residence in body, using warmth,
nutrients, and tissues to survive and reproduce — and doing great harm in the process.
A few examples of the most serious disease-causing microbes for which vaccines have
proved highly effective include the following.
Variola virus, which causes smallpox, was once the scourge of the world. This virus
passes from person to person through the air. A smallpox infection results in fever, severe aches
and pains, scarring sores that cover the body, blindness in many cases, and, often, death. In the
18th century, variola virus killed every 7th child born in Russia and every 10th child born in
Sweden and France.
The highly infectious poliovirus, the cause of polio, once crippled 13,000 to 20,000
people every year in the United States. In 1954, the year before the first polio vaccine was
introduced, doctors reported more than 18,000 cases of paralyzing polio in the United States. Just
3 years later, vaccination brought that figure down to about 2,500.
The toxic bacterium Bordetella pertussis likes to set up home in the human respiratory
tract, where it causes whooping cough, also known as pertussis. The wracking coughs
characteristic of this disease are sometimes so intense, the victims, usually infants, vomit or turn
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blue from lack of air. Before scientists created a vaccine against the bacterium, 115,000 to
270,000 people suffered from whooping cough each year in the United States; 5,000 to 10,000 of
those died from it. After the vaccine was introduced in the United States in the 1940s, the
number of pertussis cases declined dramatically, hitting a low of about 1,000 in 1976. More
recently, the annual number of reported cases of pertussis in the United States has been rising
from 9,771 in 2002 to 25,616 in 2005. The reasons for the increase are complex.
Other familiar diseases that vaccines protect against include chickenpox, hepatitis A,
hepatitis B, and Haemophil us in fl uenzae type b (Hib) . Hib causes meningitis, an inflammation
of the fluid-filled membranes that surround the brain and spinal cord. Meningitis can be fatal, or
it can cause severe disabilities such as deafness or mental retardation. Newer vaccines include
one to prevent the painful condition called shingles, which can strike anyone who has ever had
chickenpox; a vaccine against human papillomavirus, which can cause cervical cancer; and a
vaccine against rotavirus, which causes severe diarrheal disease and some 600,000 deaths in
children worldwide every year.
VACCINE-PREVANTABLE DISEASES,
VACCINES AND VACCINATION
DISEASE PREVENTION
Vaccination is a highly effective method of preventing certain infectious diseases.
For the individual, and for society in terms of public health, prevention is better
and more cost-effective than cure. Vaccines are generally very safe and adverse
reactions are uncommon. Routine immunization programmes protect most of
the world’s children from a number of infectious diseases that previously claimed
millions of lives each year. For travellers, vaccination offers the possibility of
avoiding a number of dangerous infections that may be encountered abroad.
However, vaccines have not yet been developed against several of the most lifethreatening
infections, including malaria and HIV/AIDS.
VACCINATION AND OTHER PRECAUTIONS
Despite their success in preventing disease, vaccines do not fully protect 100%
of the recipients. The vaccinated traveller should not assume that there is no risk
of catching the disease(s) against which he/she has been vaccinated. All additional
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precautions against infection should be followed carefully,
regardless of any vaccines or other medication that have been administered. These
same precautions are important in reducing the risk of acquiring diseases for
which no vaccines exist.
VACCINE SCHEDULES AND ADMINISTRATION
The vaccines that may be recommended or considered for travellers are shown in
The schedule for administration of each vaccine is given, together with
Other information for each of the vaccine-preventable diseases. Time intervals
for administration of vaccines requiring more than one dose are recommended.
The route of administration differs for individual vaccines and is critical form
induction of the protective immune response. For injectable vaccines, the routeof injection — subcutaneous, intramuscular or intradermal — determines the gauge
and length of the needle to be used.
SAFE INJECTIONS
The same high standard of injection safety should be applied to the administration
of vaccines as to any other injection. A sterile needle and syringe should be used
for each injection and disposed of safely.
WHO recommends the use of single-use (―auto-disable‖) syringes or disposable
monodose preparations whenever possible. Syringes should not be recapped (to
avoid needle-stick injuries) and should be disposed of in a way that iis safe to the
recipient, the provider and the community.
MULTIPLE VACCINES
All commonly used vaccines can be given simultaneously at separate sites at
least 2 cm apart. However, certain vaccines commonly cause local reactions,
which may be accentuated if a number of vaccines are given simultaneously.
A number of combined vaccines are now available, providing protection against
more than one disease, and new combinations are likely to become available in
future years. For routine vaccination, the combined diphtheria/tetanus/pertussis
(DTP) and measles/mumps/rubella (MMR) vaccines are in widespread use in
children. Other examples of currently available combination vaccines are hepatitis
A+B and hepatitis A + typhoid. In addition, other combination vaccines are
available in certain countries: these include IPV+DTP, IPV+DTP+Hib and
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IPV+DTP+HepB+Hib.
In adults, the combined diphtheria – tetanus vaccine (with reduced diphtheria — Td)
is generally used in preference to monovalent (single-disease) vaccine.
Combined vaccines offer important advantages for travellers, by reducing the
number of injections required and the amount of time involved, so aiding
compliance.
VACCINE BENIFITS
Once immune system is trained to resist a disease, are said to be immune to it. Before
vaccines, the only way to become immune to a disease was to actually get it and, with luck,
survive it. This is called naturally acquired immunity. In addition, during certain stages of the
illness, may be contagious and pass the disease to family members, friends, or others who come
into contact with person.
Vaccines, which provide artificially acquired immunity, are an easier and less risky
way to become immune. Vaccines can prevent a disease from occurring in the first place, rather
than attempt a cure after the fact. According to one U.S. analysis, for every dollar spent on the
measles/mumps/rubella vaccine, 21 dollars are saved.
In 1974, the Japanese government stopped vaccinating against pertussis because of
public concern about the vaccine’s safety and because no one had died from the disease the
previous year. Five years later, a pertussis epidemic in Japan sickened 13,000 people and killed
41. In 1989, low vaccination rates allowed a measles outbreak to occur in the United States. The
outbreak resulted in more than 55,000 cases of measles and 136 measles-associated deaths.
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ADVANTAGES AND DISADVANTAGES
Advantages Disadvantages
Produce a strong immuneresponse Often give lifelongimmunity with one or two doses
Remote possibility that the live microbe couldmutate back to a virulent form Must berefrigerated to stay potent
Safer and more stable than livevaccines
Produce a weaker immune response than livevaccines
Don’t require refrigeration: more
easily stored and transportedUsually require additional doses, or booster shots
Teaches the immune system tofight off bacterial toxins
Targeted to very specific parts of the microbe Fewer antigens, solower chance of adverse reactions
When developing a new vaccine, identifyingthe best antigens can be difficult and timeconsuming
Allow infant immune systems torecognize certain bacteria
Produce a strong antibody andcellular immune response
Still in experimental stages
Relatively easy and inexpensiveto produce
Closely mimic a natural infection,
stimulating a strong immuneresponse
Still in experimental stages
PRODUCTION
Two workers make openings in chicken eggs in
preparation for production of measles vaccine.
Vaccine production has several stages. First, the antigen itself is generated. Viruses are
grown either on primary cells such as chicken eggs (e.g., for influenza), or on continuous celllines such as cultured human cells (e.g., for hepatitis A). Bacteria are grown in bioreactors (e.g.,
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Haemophilus influenzae type b). Alternatively, a recombinant protein derived from the viruses or
bacteria can be generated in yeast, bacteria, or cell cultures. After the antigen is generated, it is
isolated from the cells used to generate it. A virus may need to be inactivated, possibly with no
further purification required. Recombinant proteins need many operations involving
ultrafiltration and column chromatography. Finally, the vaccine is formulated by adding
adjuvant, stabilizers, and preservatives as needed. The adjuvant enhances the immune response
of the antigen, stabilizers increase the storage life, and preservatives allow the use of multidose
vials. Combination vaccines are harder to develop and produce, because of potential
incompatibilities and interactions among the antigens and other ingredients involved.
Vaccine production techniques are evolving. Cultured mammalian cells are expected to
become increasingly important, compared to conventional options such as chicken eggs, due to
greater productivity and low incidence of problems with contamination. Recombination
technology that produces genetically detoxified vaccine is expected to grow in popularity for the
production of bacterial vaccines that use toxoids. Combination vaccines are expected to reduce
the quantities of antigens they contain, and thereby decrease undesirable interactions, by using
pathogen-associated molecular patterns. In 2010, India produced 60 percent of the world's
vaccine worth about $900 million.
EXCIPIENTS
Beside the active vaccine itself, the following excipients are commonly present in vaccine
preparations:
Aluminum salts or gels are added as adjuvants. Adjuvants are added to promote an
earlier, more potent response, and more persistent immune response to the vaccine; they allow
for a lower vaccine dosage.
Antibiotics are added to some vaccines to prevent the growth of bacteria during production and
storage of the vaccine.
Egg protein is present in influenza and yellow fever vaccines as they are prepared using chicken
eggs. Other proteins may be present.
Formaldehyde is used to inactivate bacterial products for toxoid vaccines. Formaldehyde is also
used to kill unwanted viruses and bacteria that might contaminate the vaccine during production.
Monosodium glutamate (MSG) and 2-phenoxyethanol are used as stabilizers in a few vaccines to
help the vaccine remain unchanged when the vaccine is exposed to heat, light, acidity, or
humidity.
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Thimerosal is a mercury-containing preservative that is added to vials of vaccine that contain
more than one dose to prevent contamination and growth of potentially harmful bacteria.
VACCINES OF THE FUTURE
Aside from the ―ouch factor,‖ vaccines delivered through a needle in the arm— or
elsewhere — have some shortcomings. The needles used to inject vaccines must be kept sterile,
for example, which is difficult in some settings. Also, injections usually must be administered by
trained personnel, and injecting many people quickly — as would be necessary in case of a
widespread outbreak — is not easy. For these reasons, scientists are investigating new ways to
deliver vaccines.
Although still a long way off, edible vaccines would make it cheaper and easier to
immunize people against diseases, especially in developing countries where storing and
administering vaccines is often difficult. Scientists have shown that potatoes genetically
engineered to produce an Escherichia coli antigen safely triggered an immune response to this
bacterium in people who ate small pieces of the potatoes. Similarly, a potato-based vaccine
against hepatitis B virus yielded promising results in an early stage of human testing.
Researchers have also modified bananas to protect against norovirus, a common cause of
diarrhoea, and have created a food-based vaccine containing a protein from respiratory syncytial
virus, which can cause serious respiratory illness, especially in children. Recently, research into
plant-based vaccines has focused less on food crops and more on genetically modifying plants
that are not normally eaten. Vaccine components are produced in the leaves, which are then
freeze-dried, ground up, and placed in gelatin capsules.
Another novel way being investigated to deliver vaccines simply is through a thin skin
patch. Skin is one of our best defenses against infection. But it also includes large numbers of
certain immune system cells, called dendritic cells, which can react to a vaccine placed on the
skin. Skin patch vaccines are being tested for a range of diseases, including travelers’ diarrhoea,
tetanus, anthrax, and seasonal flu.
Future vaccines may be
squirted into the nose, worn as a patch, or eaten at the dinner table.
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In 2003, the Food and Drug Administration (FDA) licensed a new vaccine for seasonal
influenza that’s delivered as spray into the nose. The vaccine, created with National Institute of
Allergy and Infectious Diseases (NIAID) support, is made from a live, attenuated flu virus. FDA
has approved it for healthy people 2 to 49 years old. The vaccine is being tested to see if it can
eventually be approved for use in older people and in children under 2 as well. Delivering this
vaccine as a nasal mist not only eliminates the needle making it easier to give to children but it
also closely mimics how the flu virus actually enters body, which may produce a better immune
response.
Nasal flu vaccine eliminates the dreaded needle, but people must still get the vaccine
every year because the circulating influenza virus strains change. Typically, vaccines prevent
infection or disease. More recently, researchers also have been creating therapeutic vaccines
intended for an existing infection or illness. Several are in various stages of development,
including ones agait some cancers, HIV, certain allergies, and multiple sclerosis.
MAKING SAFE VACCINES
No vaccine is perfectly safe or effective. Each person’s immune system works
differently, so occasionally a person will not respond to a vaccine. Very rarely, a person may
have a serious adverse reaction to a vaccine, such as an allergic reaction that causes hives or
difficulty breathing. But serious reactions are reported so infrequently — on the order of 1 in
100,000 vaccinations — that they can be difficult to detect and confirm. More commonly, peoplewill experience temporary side effects, such as fever, soreness, or redness at the injection site.
These side effects are, of course, preferable to getting the illness.
Most vaccines are designed to prevent illness and are given to people who are not sick.
To make vaccines as safe as possible, FDA requires extensive research and testing before
allowing a vaccine to be licensed for general use. The time between discovery of a disease agent
and production of a widely available vaccine has been as long as 50 years.
LAB AND ANIMAL TESTING
Also known as preclinical testing , this testing is required before the vaccine can be
given to people. Researchers test candidate vaccines in cell cultures and
in animals such as mice, rabbits, guinea pigs, or monkeys. If the vaccine
appears promising in these preclinical experiments, it may go on to be
carefully tested in people.
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INVESTIGATIONAL NEW DRUG APPLICATION
Before any vaccine candidate can be tested in people, its sponsors must submit an
Investigational New Drug (IND) application to FDA. This application must explain how the
vaccine works, describe how it is manufactured, present all preclinical safety data, and propose a
plan for human testing. The IND must also demonstrate the vaccine has passed a series of tests
for purity and safety.
STUDIES IN HUMANS
Once researchers have FDA approval to test their candidate vaccine in human volunteers,
they begin trials cautiously, starting with a very small clinical trial. If all goes well, successively
larger phases of testing will be conducted. Phase I studies enroll 20 or fewer people and
primarily test for safety. Phase II studies involve 50 to several hundred people. Phase II studies
continue to test for safety as well as to determine the best dosage and to gather preliminary data
on a vaccine’s effectiveness. A Phase III or efficacy study, designed to thoroughly test the
candidate vaccine’s power to protect against illness, involves many thousands of volunteers.
Because Phase III trials are complex and costly, researchers have introduced the
intermediary Phase IIb trial. A Phase IIb trial provides preliminary information about how well
the vaccine will work and helps researchers decide whether to move it into a Phase III trial.
Phase IIb trials enroll more volunteers than a Phase II trial but fewer than a Phase III trial. A
candidate vaccine that tests well in a Phase IIb trial would still need to be tested in a Phase III
trial. So, FDA has a rule that in developing vaccines against certain microbes, scientists can
gather efficacy information through animal rather than human tests.
FDA LICENSE
The application to FDA for a license to market a vaccine is called a Biologics License
Application (BLA). This application must provide the results of all relevant human studies,
describe all manufacturing and testing methods. A BLA must also demonstrate that the vaccine
manufacturers comply with all government standards, including those for production facilities,
personnel, equipment, packaging, and record-keeping. At this stage, FDA also inspects the
manufacturing facility.
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The BLA is reviewed first by a team of FDA experts, then by an advisory committee
made up of scientists, physicians, statisticians, and consumer representatives. The committee
votes on whether or not to recommend that FDA approve the vaccine.
NIAID VACCINE RESEARCH
Despite many accomplishments in vaccine research over the years, much remains to be
done. NIAID-supported investigators in the United States and other countries and in NIAID
laboratories in Bethesda, Maryland, and Hamilton, Montana, are working to reduce the burden of
illness through vaccines against diseases old and new.
Millions around the globe suffer illness and death from the relatively new disease
HIV/AIDS and from the ancient scourges of malaria and tuberculosis. For this reason, NIAID
has made developing new or improved vaccines for those illnesses a top priority. Other priorities
include devising vaccines against disease-causing agents that either arise naturally or that might
be deliberately released in an act of bioterrorism. Finding ways to quickly produce vaccines
against strains of influenza that experts fear may spark a pandemic is another area in which
NIAID-supported researchers are making progress.
ESTABLISHED RECORD, CONTINUING EFFORTS
Some NIAID programs in vaccine development are quite recent, while others have a
distinguished record of achievement and continue to advance the field of vaccines to this day.
In 1962, NIAID revolutionized the cumbersome, piecemeal approach to vaccine studies
by establishing a network of Vaccine and Treatment Evaluation Units. These testing sites are
based at university medical research centers, public health departments, and community clinics
across the country. VTEU investigators have also tested vaccines for pneumonia, influenza,
cholera, whooping cough, malaria, and tuberculosis. More recently, they have been called upon
to conduct critical studies of smallpox vaccines and pandemic flu.
In 1988, the world’s first HIV vaccine trial began at the National Institutes of Health in
Bethesda. That same year, NIAID established the AIDS Vaccine Evaluation Group (AVEG). In
1999, NIAID built upon AVEG by creating the HIV Vaccine Trials Network (HVTN).The
international sites enable studies that examine differences in genetic makeup, nutrition, access to
health care, and HIV subtypes in various populations, all crucial factors in creating a vaccine that
is effective worldwide.
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In 2000, NIAID established the Dale and Betty Bumpers Vaccine Research Center
(VRC) in Bethesda. At the VRC, vaccines can be developed from initial concept to final
product.VRC scientists work on vaccines against multiple microbes, with an emphasis on
developing therapeutic and preventive vaccines against HIV. A new prime-boost vaccine
targeted at multiple HIV subtypes, which was developed at the VRC, entered a Phase II clinical
trial in 2005, while the first human trial of an Ebola vaccine began in the center’s clinic in 2003.
In 2006, the world’s first human trial of a DNA vaccine against the H5N1 avian influenza
opened to volunteers.
NIAID is currently supporting the creation of a national network of laboratories that will
augment our nation’s capacity to develop vaccines against infectious agents, whether they arise
naturally, such as West Nile virus, SARS (severe acquired respiratory syndrome), and
tuberculosis, or are deliberately introduced. NIAID-funded scientists are developing improved
vaccines against smallpox, anthrax, plague, avian flu, and other emerging disease threats.
Established by NIAID in 2005, the Center for HIV/AIDS Vaccine Immunology
(CHAVI) is a consortium of researchers based at institutions across the country who are working
together to tackle some of the biggest obstacles in developing an HIV vaccine. Scientists
working on vaccines also have advanced technology to draw on, including recombinant DNA
technology and the ability to ―read‖ and analyze the genomes of disease-causing organisms. This
new knowledge and technology promises to usher in a renaissance in the already vital field of
vaccinology.
FOLLOW-UP SURVEILLANCE
Once a vaccine is on the market, FDA continues to monitor its safety. FDA periodically
inspects the manufacturing facility, and it tests samples of the vaccine for potency, safety, and
purity. The manufacturer must also safety test each batch, or lot, of the vaccine. In addition, most
licensed vaccines continue to be evaluated with very large studies that look at tens of thousands
of people who have received the vaccine. These Phase IV studies try to pick up rare or delayed
adverse reactions that might not have been apparent in the smaller studies that led to licensure.
Finally, FDA and CDC gather information on licensed vaccines through the Vaccine
Adverse Events Reporting System (VAERS). Anyone — health care providers, patients,
parents — can report adverse vaccine reactions to VAERS. FDA reviews weekly VAERS reports
for each lot of vaccine in use, searching for anything unusual.
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CONCLUSION:
The vaccines are mainly 38 vaccines especially for childrens by newer technology
provides the natural vaccines and showing the much better action. The nano technology also
provides the new methods for making vaccines for the some other diseases. With improved
vaccines and expanded knowledge about immunology, the way we prevent against disease has
changed.
REFERENCES
• Stefan Riedel, MD, PhD (January 2005). "Edward Jenner and the history of smallpox and
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• Grammatikos, Alexandros P.; Mantadakis, Elpis; Falagas, Matthew E. (June 2009). "Meta-
analyses on Pediatric Infections and Vaccines". Infectious Disease Clinics of North America
Vol: 23 (2): Pp-431 – 57. doi:10.1016/j.idc.2009.01.008.
• Bmj.bmjjournals.com. Retrieved 2013-04-26. Cohort study journals - Schlegeletal.
"Comparative efficacy of three mumps vaccines during disease outbreak in eastern Switzerland:
Vol:58(6) Pp-319 (7206): 352 - bmj.co
• Halloran, M.E. (2003). Clinical Infectious Diseases (Oxford Journals) 37(6) "Effects of PertussisVaccination on Disease: Vaccine Efficacy in Reducing Clinical Severity".
• Orenstein WA, Papania MJ, Wharton ME (2004). "Measles elimination in the United States".
Vol:84 Pp-496 – 684 doi:10.1086/377693.