Understanding Vaccine Safety: Immunization
Remains Our Best Defense Against Deadly Disease
Smallpox and polio have been wiped out
in the United States. Cases of measles, mumps, tetanus,
whooping cough (pertussis) and other life-threatening
illnesses have been reduced by more that 95 percent.
Immunization against influenza and pneumonia prevent
tens of thousands of deaths annually among elderly
persons and those who are chronically ill. As a result,
millions of lives have been saved. But don't let the
success of vaccines fool you into thinking we no longer
need them. Most vaccine-preventable diseases aren't
Steve Berman, M.D., president of the
American Academy of Pediatrics and a pediatrician
in Denver, says he and his colleagues were devastated
to recently see an infant die of whooping cough. "This
was a case where the family thought the risks of vaccination
outweighed the benefits," Dr. Berman says. The
baby was exposed to the disease by two older brothers
who hadn't been vaccinated.
Vaccines contain a weakened (attenuated)
or killed (inactivated) form of disease-causing bacteria
or viruses, or components of these microorganisms,
that trigger a response by our body's immune system.
For example, vaccines stimulate our bodies to make
antibodies--proteins that specifically recognize and
target the bacteria and viruses against which the
vaccines are designed, and that help eliminate them
from the body when we encounter them.
Without vaccine protection, we can easily
contract and transmit infectious diseases. It may
only take one person, whether it's a family member,
a neighbor, or a visitor from another country, to
start the spread of a disease. And even immunized
individuals can be at risk because no vaccine is ever
100 percent effective for everyone.
Most parents believe in the benefits
of vaccination, as evidenced by record high childhood
vaccination rates, and more and more adults are getting
vaccinated against influenza, pneumococcal disease,
and tetanus. But some people who need vaccines don't
get them for a variety of reasons, including fear
of side effects. Lately, a surge of negative publicity
focusing on the risks of vaccines--some of which are
unproven or inaccurate--has some wondering whether
they do more harm than good. But vaccine experts and
the overwhelming majority of health-care providers
caution consumers against skipping important vaccinations
because of an evening news report or a posting on
Sometimes such reports contain unsubstantiated
or inaccurate information and don't reflect a balanced
view of the risks and benefits of a particular vaccine.
The Food and Drug Administration recommends
that consumers arm themselves with the facts about
the benefits and risks of vaccines, along with the
potential consequences of not vaccinating against
certain diseases. According to a Washington state-based
organization called Parents of Kids with Infectious
Diseases (PKIDS), some parents are shocked to learn
that children can die of chickenpox and other vaccine-preventable
diseases they hadn't considered a threat.
The FDA's Center for Biologics Evaluation
and Research (CBER) regulates vaccines in the United
States, and works with several other agencies, including
the Centers for Disease Control and Prevention (CDC)
and the National Institutes of Health (NIH), to study
and monitor vaccine safety and effectiveness. New
vaccines are licensed only after the FDA thoroughly
reviews the results of extensive laboratory studies
and clinical trials performed by scientists, physicians,
For vaccines intended for wide use in
healthy populations such as children, clinical testing
with careful safety monitoring typically involves
thousands of patients before a vaccine is ever licensed.
And after a vaccine hits the market, the safety monitoring
continues, as does FDA oversight to assure the highest
levels of quality control in the vaccine production
"We are always monitoring for evidence
that might suggest possible problems with vaccines,"
says Karen Midthun, M.D., director of CBER's office
of vaccine research and review. CBER scientists also
conduct research to better ensure vaccine safety and
to better understand vaccine-related side effects.
A Commitment to Safety
On the surface, it may seem that approaching
vaccine safety as a continuous process--always looking
into problems and potential problems--implies that
vaccines are unsafe. "But it's actually a reflection
of our ongoing commitment to safety, and to assuring
the prevention of potentially lethal infectious diseases,"
says Jesse Goodman, M.D., M.P.H., deputy director
for medicine at CBER. "It's also the nature of
science to seek and implement improvements which make
for safer and more effective medical products."
Since 1996, for example, CBER has licensed
several acellular pertussis vaccines. Acellular pertussis
vaccines use only parts of the disease-causing bacteria
and are associated with fewer side effects than the
whole cell pertussis vaccines that had been in use.
In 1997, the CDC's Advisory Committee on Immunization
Practices (ACIP) recommended a switch from using the
whole cell pertussis component of the diphtheria,
tetanus, pertussis (DTP) vaccine to using acellular
pertussis vaccines for all five doses in the childhood
schedule (see "Recommended Childhood Immunization
The National Institute of Allergy and
Infectious Diseases (NIAID) sponsored clinical trials
for some of the experimental acellular vaccines. "We
set out to develop an improved vaccine that would
be as effective as the standard whole cell vaccine
but cause less extended crying, fevers, and other
side effects," says Carole Heilman, Ph.D., director
of NIAID's division of microbiology and infectious
diseases. CBER scientists also played a critical role
by developing methods to evaluate the acellular vaccines,
which helped them get to clinical trials faster.
There have been other recent policy
changes to improve vaccine safety, including ACIP's
1999 recommendation to change from the use of oral
polio vaccine (OPV) to the inactivated polio virus
(IPV). OPV had been highly effective in controlling
naturally occurring polio outbreaks, preventing thousands
of cases of paralysis a year. But as a live virus,
it mutated in extremely rare cases to cause polio
itself. Continued use of OPV resulted in about 10
cases of paralytic polio each year among millions
vaccinated and their contacts, according to William
Egan, Ph.D., deputy director of CBER's office of vaccine
research and review. Switching to the use of IPV eliminated
this risk and was appropriate once epidemic polio
"There are times when we also take
action even when there is just the theoretical potential
for harm," Goodman says. Thimerosal, a mercury-containing
compound, had been the most widely used preservative
in vaccines. Its use in minute amounts helped to prevent
bacteria from contaminating multi-dose vials of vaccines
and other medicines, protecting against potentially
serious infections. But thimerosal has been nearly
eliminated from vaccines because of legitimate and
growing scientific concerns about the possible effects
of mercury on the nervous system, Goodman says.
"In addition, as the numbers of
vaccines used in children have increased, small infants
who received every recommended vaccine could be exposed
to cumulative doses of mercury that exceeded some,
but not all, federal guidelines," Goodman explains.
Even though there are no convincing
data that show harm because of thimerosal in vaccines,
the U.S. Public Health Service recommended moving
rapidly to vaccines that are thimerosal-free. The
FDA encouraged manufacturers to comply and set the
highest priority for its reviews of such products,
Goodman says. As a result, all recommended pediatric
vaccines available are now thimerosal free or have
greatly reduced thimerosal contents. In March 2001,
the FDA approved a newly formulated version of Tripedia,
a diphtheria and tetanus toxoids and acellular pertussis
(DTAP) vaccine with only a trace amount of thimerosal.
A Thorough Process
The most common components of vaccines
are weakened microbes (disease-causing microorganisms),
killed microbes, and inactivated toxins. In addition,
subunit vaccines, which only use a part of the bacterium
or virus, are increasingly being used.
Manufacturers conduct stringent tests
to make sure that cell lines used for producing viral
vaccines do not contain adventitious agents (unwanted
viruses) such as simian virus 40 (SV40), which was
found in some early polio vaccines. These vaccines
had been manufactured in kidney cells from simians
(monkeys) that harbored SV40. Following its discovery,
SV40 was removed from vaccines, and vaccines have
been free of the virus since the early 1960s. CBER
scientists are developing potentially better methods
to detect such infectious agents.
Developing vaccines is a thorough and
rigorous process, Egan says. Vaccines are tested for
safety on animals first, and then in humans during
several phases of clinical trials. The most important
clinical trial for the recently licensed vaccine Prevnar
involved nearly 40,000 people, equally divided between
those who received the vaccine and those who did not.
Prevnar was approved to prevent invasive pneumococcal
diseases such as meningitis.
A group of FDA scientists reviews data
and the proposed labeling of the vaccine, which includes
directions for use and information about potential
side effects. The committee also reviews manufacturing
protocols, conducts its own tests, and inspects the
manufacturing facility. The FDA's Vaccines and Related
Biological Products Advisory Committee, which includes
scientific experts and consumer representatives, can
be consulted at any time to review data and recommend
action to the agency.
After a vaccine is licensed, the FDA
generally requires that manufacturers use validated
methods to test samples from each vaccine lot for
safety, potency, and purity prior to its release for
public use. The FDA also tests selected lots and products
to help assure the accuracy of tests conducted by
"Most vaccines cause some side
effects, but they are usually minor and short-lived
like low-grade fever and soreness at the injection
site," Midthun says. Serious vaccine reactions--causing
disability, hospitalization, or death--are extremely
rare but they can happen.
Like any medicine, vaccines carry a
small risk of serious harm such as severe allergic
reaction. But experts point out that the risk of being
harmed by a vaccine is much lower than the risk that
comes with infectious diseases.
For example, in 1976, the swine influenza
(flu) vaccine was associated with a severe paralytic
illness called Guillain-Barré Syndrome (GBS).
According to the CDC's vaccine information sheet on
the influenza vaccine, "if there is a risk of
GBS from current influenza vaccines, it is estimated
at 1 or 2 cases per million persons vaccinated, much
less than the risk of severe influenza, which can
be prevented by vaccination." Each year, flu
causes tens of thousands of deaths, mostly among older
people. Most people who get the influenza vaccine
have no serious problem from it.
And though some people worry about it,
you can't get the flu from the flu vaccine, Midthun
says. "Just as there are no vaccines that are
100 percent safe, there are also none that are 100
percent effective," she says. "So you may
get the flu soon after you received the vaccine, before
it could be expected to protect you. It does not mean
the shot gave you the flu," she says.
Some live virus vaccines, such as the
chickenpox vaccine, can cause mild versions of the
disease they protect against, says Goodman. "But
this is usually only a serious problem if the patient
has a severely compromised immune system." And
vaccines are generally not advised for such people.
It's important to talk with your doctor about the
benefits and risks of vaccines, and any concerns you
may have, specifically as it relates to you and your
family. If you or your child has previously had a
significant reaction to a vaccine, that may affect
the risk/benefit ratio for the individual and whether
that vaccine should be recommended again.
How Reactions Are Evaluated
Before a vaccine is put into standard
medical practice, it must be studied in clinical trials
of thousands of people, which allows for evaluation
of relatively common side effects. For example, a
common side effect might occur in one or more of several
hundred vaccine recipients. But rare events (fewer
than one case in several thousand recipients) aren't
usually evident in clinical trials. "Unless you've
studied something in a million or more people, you
might never see the very rare event or be able to
know whether it occurred due to vaccination or simply
by chance," Goodman says.
Through the Vaccine Adverse Event Reporting
System (VAERS), jointly operated by the FDA and the
CDC to monitor the safety of licensed vaccines, experts
look for patterns and any unusual trends that may
raise questions about a vaccine's safety once it is
used more widely in the population. The FDA continuously
reviews and evaluates individual reports, in addition
to monitoring overall reporting patterns. The FDA
also monitors reporting trends for individual vaccine
lots. Most reports come from health-care providers,
but anyone can report an unexpected event after vaccination
VAERS receives 800 to 1,000 reports
each month. Because it often can't be determined whether
an adverse event occurring after vaccination was actually
caused by the vaccination, health-care providers and
consumers are encouraged to report any event that
might be attributable to a vaccine.
"You don't have to be sure,"
says Susan Ellenberg, Ph.D., director of CBER's office
of biostatistics and epidemiology. "Reporting
possible reactions will help identify adverse events
that might be truly associated with vaccinations and
need further study." But this approach to reporting
means that one can't assume that all VAERS reports
describe true vaccination reactions.
VAERS is a passive, voluntary reporting
system, which means not all adverse events get reported.
It also means that many reports are incomplete or
even contain inaccurate information because the forms
are not filled out by trained personnel. Another problem
with interpreting VAERS data is the lack of information
on the total number of individuals who received a
particular vaccine, making it impossible to estimate
the incidence of reported adverse events. It's also
often the case that multiple vaccines are given at
the same time, further complicating the interpretation
of what might have caused the event, Ellenberg says.
Despite these problems, VAERS does contribute
in important ways to understanding vaccine safety.
VAERS data may suggest the need for more research
on certain vaccines. "In this sense, VAERS is
a signal generator," Egan says. Recently, VAERS
data were instrumental in evaluating RotaShield, a
vaccine licensed to protect against rotavirus infection.
Rotavirus is the most common cause of gastroenteritis
in children younger than five and can result in severe
diarrhea, dehydration, and death. This virus is an
especially serious problem in developing nations,
where it kills hundreds of thousands of children every
Following the vaccine's licensure, VAERS
started to receive reports of bowel obstruction in
a number of infants who had received RotaShield. Careful
review of these reports revealed that the bowel obstruction
occurred most often in the first two weeks after RotaShield
was administered. As a result, the CDC recommended
postponing any further distribution or administration
of RotaShield until more data could be collected and
The FDA discussed the concerns with
the manufacturer, which decided to voluntarily withdraw
the product from use. In November 1999, ACIP withdrew
its previous recommendation for universal use of the
vaccine. At this time, the FDA, NIH, and CDC are still
studying the bowel obstruction and RotaShield-associated
cases, Egan says. "We continue to look into mechanisms
for any serious adverse events. We want to understand
why they happen so that we can prevent them from occurring
in the future."
The CDC's Vaccine Safety DataLink, which
links computerized histories of vaccination to hospitalization
records and other medical information for members
of eight large managed care organizations, supplements
the information in VAERS and permits more rigorous
evaluation of possible safety concerns. For example,
the system allows researchers to compare how often
an adverse event occurs in people recently vaccinated
with those not recently vaccinated, to evaluate the
likelihood that the vaccine caused the adverse event.
Some have looked to vaccines to explain
a host of serious conditions that we don't fully understand,
including sudden infant death syndrome (SIDS), multiple
sclerosis, diabetes, and autism. There have been a
number of epidemiological studies of these possible
associations, and experts say there is no good scientific
evidence at this time showing that vaccines cause
these diseases or conditions.
"Physicians give vaccines to children
at multiple time points during their development and
a lot can happen during that time," says Midthun.
She stresses that both the FDA and the CDC take concerns
of parents seriously. After careful review of all
available information, neither agency has found that
existing data support any link between the measles,
mumps, and rubella (MMR) vaccines and autism, a hypothesis
that has received considerable publicity over the
The CDC and the NIH recently contracted
with the Institute of Medicine, part of the National
Academy of Sciences, to establish the Immunization
Safety Review Committee. The independent committee
is charged with evaluating nine vaccine safety topics
over a three-year span. The possible association of
the MMR vaccine and autism was the first topic.
On April 23, 2001, the Immunization
Safety Review Committee reported its finding that
the current evidence does not favor the hypothesis
that there is a link between MMR and autism, and that
no changes should be made in the current policy of
administering the MMR vaccine. The committee could
not rule out the possibility that the MMR vaccine
might be linked to autism in some sub-population,
and recommended that targeted research in this area
be conducted. To date, there is no indication as to
whether there is any such subpopulation, or what the
genetic makeup or other characteristics of such a
subpopulation would be, Egan says.
"It's important that policy decisions
about vaccine safety be based on science," says
Martin G. Myers, M.D., director of the U.S. Department
of Health and Human Service's National Vaccine Program
Office. As vaccine safety research continues, Myers
says, we can't afford to lose sight of what life was
like before immunization. Vaccination is the reason
we don't see the suffering, disability, and death
from whooping cough, measles, polio and other infectious
diseases like we used to.
"Vaccines are very safe,"
Myers adds, "but nothing is without risk."
Not vaccinating against certain diseases means choosing
another type of risk, he says. Myers recalls treating
an infant with seizures from tetanus so strong they
shook the baby's whole body. These types of seizures
and many deaths are preventable by vaccination. And
Myers still has an audiotape from the early eighties
of a child hacking and gasping for air because of
whooping cough. "The child's mother asked me
to play it for parents who might be undecided about
getting vaccinated." He's also played the tape
for medical students and residents. "It doesn't
take long before somebody in the room asks me to please
turn it off."
National Vaccine Injury Compensation Program
The National Vaccine Injury Compensation
Program became effective in 1988. The program is a
federal "no-fault" system designed to compensate
those individuals, or families of individuals, who
have been injured by childhood vaccines. A claim may
be made for any injury or death thought to be the
result of a vaccine covered under the program. The
program is administered jointly by the U.S. Department
of Health and Human Services, the U.S. Court of Federal
Claims, and the U.S. Department of Justice.
Steps to Take When You Vaccinate
- Review the vaccine information sheets that
explain the potential risks of each vaccine. Health
practitioners are required by law to provide them.
- Talk to your doctor about whether certain reactions
to vaccines can be controlled. For example, fever
may be prevented or reduced by taking acetaminophen
before or after vaccination.
- Tell your doctor if you, your child, or a sibling
has ever had a bad reaction to a vaccine.
- Ask your doctor about conditions under which
you or your child should not be vaccinated. This
might include being sick or having a history of
certain allergic or other adverse reactions to
previous vaccinations or their components, such
as allergies to eggs, which are used to grow influenza
- Report unexpected events after vaccinations
to your doctor and to the Vaccine Adverse Event
Reporting System (VAERS) at 1-800-822-7967.
For More Information
National Immunization Hotline:
1-800-232-2522 (English) or