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 gone.
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 the Internet.
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, and manufacturers.
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 process.
"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 Schedule").
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
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
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
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 the manufacturers.
"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
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
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 to VAERS.
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 year.
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 evaluated.
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 last
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 vaccines.
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