Understanding nderstanding

VACCINES VACCINES


What They Are How They Work What They Are How They Work

U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES 

National Institutes of Health 

National Institute of Allergy and Infectious Diseases 
Understanding nderstanding

VACCINES VACCINES


What They Are How They Work What They Are How They Work

U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES 

National Institutes of Health 

National Institute of Allergy and Infectious Diseases 

NIH Publication No. 08-4219 

January 2008 

www.niaid.nih.gov 
Contents
 

Introduction 

2 

4 

6 

11 

21 

36 

38 

43 

47 

48 

1 

What Is a Vaccine? 

Vaccine Benefits 

Harmful Microbes 

How Vaccines Work 

Different Types of Vaccines 

Vaccines of the Future 

Making Safe Vaccines 

NIAID Vaccine Research 

More Information 

Glossary 
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
 

UNDERSTANDING VACCINES 1
 
What Is aVaccine?
 

Chances are you never had diphtheria. You probably 

don’t know anyone who has suffered from this disease, 

either. In fact, you may not know what diphtheria is, 

exactly. (To find out, see “Diphtheria: Remembering an 

Old Disease” on page 3.) Similarly, diseases like whooping 

cough (pertussis), measles, mumps, and German measles 

(rubella) may be unfamiliar to you. 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. The names of these 

diseases were frightening household words. Today, they 

are all but forgotten. That change happened largely 

because of vaccines. 

Chances are you’ve been vaccinated against diphtheria. 

You even may have been exposed to the bacterium that 

causes it, but the vaccine prepared your body to fight off the 

disease so quickly that you were unaware of the infection. 

Vaccines take advantage of your body’s natural ability 

to learn how to eliminate almost any disease-causing 

germ, or microbe, that attacks it. What’s more, your body 

“remembers” how to protect itself from the microbes it 

has encountered before. Collectively, the parts of your 

body that recall and repel microbes are called the immune 

system. (We’ll take a closer look at the immune system 

in the section “How Vaccines Work” on page 11.) Without 

the immune system, the simplest illness—even the 

common cold—could quickly turn deadly. On average, 

2 Note: Words in bold are defined in the glossary at the end 

of this booklet. 
Diphtheria: Remembering 

an Old Disease 

your immune system takes more 

than a week to learn how to fight off 

an unfamiliar microbe. Sometimes 

that isn’t soon enough. Stronger 

microbes can spread through your 

body faster than the immune system 

can fend them off. Your body often 

gains the upper hand after a few 

weeks, but in the meantime you are 

sick. Certain microbes are so 

powerful, or virulent, that they can 

overwhelm or escape your body’s 

natural defenses. In those situations, 

vaccines can make all the difference. 

Traditional vaccines contain either 

parts of microbes or whole microbes 

that have been killed or weakened so 

that they don’t cause disease. When 

your immune system confronts these 

harmless versions of the germs, it 

quickly clears them from your body. 

In other words, vaccines trick your 

immune system but at the same time 

teach your body important lessons 

about how to defeat its opponents. 

UNDERSTANDING VACCINES 
3 

In 1900, diphtheria killed more 

people in the United States than 

cancer did. Caused by the toxic 

bacterium Corynebacterium 

diphtheriae, this upper airway 

infection often results in a grayish, 

thick membrane that grows in the 

throat and obstructs breathing. 

Other symptoms include fever, 

hoarseness, and coughing. Most 

diphtheria deaths resulted not from 

blocked airways but from the 

paralyzing toxin the bacterium 

secretes, which can cause the heart 

or other organs to fail. During the 

1990s, on average, only three 

diphtheria cases among U.S. 

residents were reported each year. 
Vaccine Benefits
 

You and Your Community 

Once your immune system is trained to resist a disease, 

you 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. With naturally acquired immunity, 

you suffer the symptoms of the disease and also risk the 

complications, which can be quite serious or even deadly. 

In addition, during certain stages of the illness, you may 

be contagious and pass the disease to family members, 

friends, or others who come into contact with you. 

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. It is much 

cheaper to prevent a disease than to treat it. According 

to one U.S. analysis, for every dollar spent on the 

measles/mumps/rubella vaccine, 21 dollars are saved. 

Vaccines protect not only yourself but also others around 

you. If your vaccine-primed immune system stops an 

illness before it starts, you will be contagious for a much 

shorter period of time, or perhaps not at all. Similarly, 

when other people are vaccinated, they are less likely 

to give the disease to you. So vaccines protect not only 

individuals, but entire communities. That is why vaccines 

are vital to the public health goal of preventing diseases. 

4 
If a critical number of people within 

a community are vaccinated against 

a particular illness, the entire group 

becomes less likely to get the disease. 

This protection is called community 

immunity, or herd immunity. 

On the other hand, if too many 

people in a community do not get 

vaccinations, diseases can reappear. 

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. 

Community immunity: If enough people 

in a community are vaccinated against 

a particular illness, the entire group 

becomes less likely to get the disease, 

even those who are not vaccinated. 

Passive Immunity 

Passive immunity is another way 

to gain some protection against 

disease. It is immunity transferred 

from one person to another. Babies, 

for example, gain passive immunity 

to some diseases from the 

antibodies that are passed to them 

from their mothers before birth or 

through breastfeeding. This kind of 

immunity lasts only a few weeks or 

months. Another form of passive 

immunity is generated by giving a 

person purified blood serum, which 

contains the antibodies produced 

after someone successfully fights 

off an illness. In 2003, researchers 

began a clinical trial in the United 

States to test whether antibodies 

against West Nile virus can be used 

to treat people who suffer from the 

most severe form of this mosquitoborne illness. (In that trial, passive 

immunity is used to treat infection, 

rather than prevent it.) 

UNDERSTANDING VACCINES 
5 
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 your digestive 

tract are, in fact, beneficial. But other microbes break into 

and take up residence in your body, using your warmth, 

nutrients, and tissues to survive and reproduce—and doing 

you 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. 

6 
Although vaccination and 

outbreak control had eliminated 

smallpox in the United States 

by 1949, the disease still struck 

an estimated 50 million people 

worldwide each year during the 

1950s. In 1967, that figure fell to 

10 to 15 million because of 

vaccination. That same year, 

the World Health Organization 

(WHO) launched a massive 

vaccination campaign to rid 

the world of smallpox—and 

succeeded. The last case of 

naturally occurring smallpox 

was in Somalia in 1977. 

• 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. Today, the 

disease has been eliminated from 

the Western Hemisphere, and 

public health officials hope to 

soon eradicate it from the globe. 

In 2006, 2,000 cases of polio were 

reported worldwide, according 

to WHO. 

U.S. Vaccine-Preventable 

Infectious Diseases 

Anthrax 

Bacterial meningitis 

Chickenpox 

Diphtheria 

Haemophilus influenzae type b 

Hepatitis A 

Hepatitis B 

Cervical cancer (caused by 

human papillomavirus) 

Influenza 

Japanese encephalitis 

Measles 

Mumps 

Pertussis 

Pneumococcal pneumonia 

Polio 

Rotavirus diarrhea 

Rabies 

Rubella 

Smallpox 

Shingles 

Tetanus 

Tuberculosis 

Typhoid 

Yellow fever 

UNDERSTANDING VACCINES 
7 
• 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 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. The disease 

strikes in cycles, and the immunity provided by 

the vaccine wanes over time, leaving some people 

susceptible in their teen years and as adults. 

Other familiar diseases that vaccines protect against include 

chickenpox, hepatitis A, hepatitis B, and Haemophilus 

influenzae 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. This disease has nearly disappeared among 

babies and children in the United States since the Hib 

vaccine became widely used in 1989. 

8 
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. 

UNDERSTANDING VACCINES 9
 
10 

The word “vaccine” comes from the Latin word vaccinus, 

which means “pertaining to cows.” What do cows have to do 

with vaccines? The first vaccine was based on the relatively 

mild cowpox virus, which infected cows as well as people. 

This vaccine protected people against the related, but much 

more dangerous, smallpox virus. 

More than 200 years ago, Edward 

Jenner, a country physician 

practicing in England, noticed that 

milkmaids rarely suffered from 

smallpox. The milkmaids often did 

get cowpox, a related but far less 

serious disease, and those who 

did never became ill with smallpox. 

In an experiment that laid the 

foundation for modern vaccines, Jenner took a few drops of 

fluid from a skin sore of a woman who had cowpox and 

injected the fluid into the arm of a healthy young boy who 

had never had cowpox or smallpox. Six weeks later, Jenner 

injected the boy with fluid from a smallpox sore, but the boy 

remained free of smallpox. 

Dr. Jenner had discovered one of the fundamental principles 

of immunization. He had used a relatively harmless foreign 

substance to evoke an immune response that protected 

someone from an infectious disease. His discovery would ease 

the suffering of people around the world and eventually lead 

to the elimination of smallpox, a disease that killed a million 

people, mostly children, each year in Europe. By the beginning 

of the 20th century, vaccines were in use for diseases that 

had nothing to do with cows—rabies, diphtheria, typhoid fever, 

and plague—but the name stuck. 

Dr. Edward Jenner 

What Do Cows Have to Do with Vaccines? 
How Vaccines Work
 

The Immune System 

To understand how vaccines teach your body to fight 

infection, let’s first look at how the immune system 

fends off and learns from a naturally occurring infection. 

Then we’ll examine how vaccines mimic this process. 

Imagine you are a dock worker on the piers of Philadelphia. 

The year is 1793. As you are unloading crates of tea and 

spices from an oceangoing ship, a mosquito bites you on 

the arm. This mosquito carries the virus that causes 

yellow fever, which the mosquito picked up when it bit 

a sailor who recently returned from Africa. So now you 

have thousands of yellow fever viruses swarming into 

your body. In fact, you have become part of an infamous 

epidemic that will claim the lives of 10 percent of the 

people in Philadelphia, and all that stands between you 

and a fatal case of yellow fever is your immune system. 

Your immune system is a complex network of cells and 

organs that evolved to fight off infectious microbes. 

Much of the immune system’s work is carried out by an 

army of various specialized cells, each type designed to 

fight disease in a particular way. The invading viruses 

first run into the vanguard of this army, which includes 

big and tough patrolling white blood cells called 

macrophages (literally, “big eaters”). The macrophages 

grab onto and gobble up as many of the viruses as they 

can, engulfing them into their blob-like bodies. 

UNDERSTANDING VACCINES 11
 
A mosquito bite transmits the yellow fever virus to an 

unsuspecting dock worker. In 1793, a yellow fever 

epidemic claimed the lives of 10 percent of Philadelphians. 

How do the macrophages recognize the yellow fever 

virus? All cells and microbes wear a “uniform” made up 

of molecules that cover their surfaces. Each of your cells 

displays marker molecules unique to you. The yellow 

fever viruses display different marker molecules unique 

to them. The macrophages and other cells of your 

immune system use these markers to distinguish among 

the cells that are part of your body, harmless bacteria 

that reside in your body, and harmful invading microbes 

that need to be destroyed. 

12 
The molecules on a microbe that identify it as foreign 

and stimulate the immune system to attack it are called 

antigens. Every microbe carries its own unique set of 

antigens, and, as we will see, they are central to creating 

vaccines. 

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 your 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. 

By this time, about 3 days after the mosquito bite, you 

are feeling feverish and have a headache. You decide to 

stay home from work. 

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 your 

yellow fever. T cells and B cells head up the two main 

divisions of the immune system army. 

UNDERSTANDING VACCINES 13
 
T Cells 

T cells function either offensively or defensively. The 

offensive T cells don’t attack the virus directly, but they 

use chemical weapons to eliminate the cells of your 

body already infected with the yellow fever virus. (See 

“How Viruses Work,” page 20.) 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 killer T cells latch onto these cells and release 

chemicals that destroy the infected cells and the viruses 

inside. 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. Helper T cells 

assist in activating killer T cells, and helper T cells also 

stimulate and work closely with B cells. 

The work done by T cells is called your 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. Antibodies and antigens fit 

together like pieces of a jigsaw puzzle—if their shapes 

are compatible, they bind to each other. 

14 
Each antibody can usually fit with only one antigen. 

So your immune system keeps a supply of millions and 

possibly billions of different antibodies on hand to be 

prepared for any foreign invader. Your immune system 

does this by constantly creating millions of new B cells. 

About 50 million B cells circulate in each teaspoonful of 

your blood, and almost every B cell—through random 

genetic shuffling—produces a unique antibody that it 

displays on its surface. 

Before you contracted yellow fever, somewhere in your 

body B cells were probably circulating with antibodies 

that, purely by chance, matched antigens from the yellow 

fever virus. When these B cells 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 

your 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. When antibodies gather on the surface of 

a microbe, it is bad news for the microbe. The microbe 

becomes generally bogged down, gummed up, and unable 

to function. 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!” Antibodies also work with other 

defensive molecules that circulate in the blood, called 

complement proteins, to destroy microbes. 

UNDERSTANDING VACCINES 15
 
Your immune system is a complex 

network of cells and organs. Cells 

called macrophages gobble up the 

invading virus and sound the alarm 

by showing pieces of the invader 

to T cells and B cells. B cells 

produce defensive molecules 

called antibodies that “stick” 

to the virus. 

Macrophage 

T cell 

T cell 

Virus 

B cell Antibodies 

B cell 

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 by antibodies alone, 

without any help from killer T cells. 

Clearing the Infection: Memory 

Cells and Natural Immunity 

While your immune system works to rid your body of 

yellow fever, you feel awful. You lie in bed, too dizzy and 

weak even to sit up. During the next several days, your 

skin becomes yellow (or jaundiced) and covered with 

purple spots. You vomit blood. Your doctor looks grim 

and tired: He knows that as many as 20 percent of people 

who contract yellow fever die, and the epidemic is 

spreading fast through the city. 

16 
To overcome the virus, B cells 

turn into plasma cell “factories” 

that produce antibodies. Cytotoxic

T cells eliminate cells infected 

with the virus; helper T cells 

direct the action with chemical 

signals. 

Infected 

cell 

Infected

cell

Cytotoxic 

T cell 

B cell 

Plasma 

cell 

Helper 

T cell 

Antibodies 

Plasma 

cell 

Virus 

You are one of the lucky ones, though. After about a 

week, your immune system gains the upper hand. Your 

T cells and antibodies begin to eliminate the virus faster 

than it can reproduce. Gradually, the virus disappears 

from your body, and you feel better. You get out of bed. 

Eventually, you go back to working the docks. 

If you are ever bitten by another mosquito carrying the 

yellow fever virus, you won’t get the disease again. You 

won’t even feel slightly sick. You have become immune 

to yellow fever because of another kind of immune 

system cell: memory cells. After your body eliminated 

the disease, some of your yellow-fever-fighting B cells 

and T cells converted into memory cells. These cells will 

circulate through your body for the rest of your life, ever 

watchful for a return of their enemy. Memory B cells can 

quickly divide into plasma cells and make more yellow 

UNDERSTANDING VACCINES 17 
fever antibody if needed. Memory T cells can divide and 

grow into a yellow-fever-fighting army. If that virus 

shows up in your body again, your immune system will 

act swiftly to stop the infection. 

How Vaccines Mimic Infection 

Vaccines teach your 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 you 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 your 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. (More on how vaccine 

makers create vaccines a little later.) This vaccine is 

injected into your arm. Your 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 your immune 

system swings into action. Yellow-fever-specific T cells 

rush out to meet the foe. B cells secrete yellow fever 

antibodies. But the battle is over quickly. The weakened 

18 
viruses in the vaccine can’t put up much of a fight. The 

mock infection is cleared, and you are left with a supply 

of memory T and B cells to protect you against yellow 

fever, should a mosquito carrying the virus ever bite you. 

Next, we’ll take a closer look at different types of 

vaccines—not all of them employ killed or weakened 

microbes—and learn how each type works. 

UNDERSTANDING VACCINES 19
 
20 

How Viruses Work 

Viruses such as the yellow fever virus are 

tiny microbes made up of a small number 

of genes encased in a membrane or protein 

shell. If you were the size of a cell, a virus 

would look like a burr (a small, round 

object covered with tiny bristles) attached 

to your pants leg. 

Like burrs, viruses stick to cells. Then they 

inject their genetic material inside the cells. 

Once inside, the virus genes take over the 

cells’ resources and molecular machinery, 

forcing the cells to make more viruses. 

The newly formed viruses “bud”—or are 

released from the surface of the cells and 

drift off to infect new cells. Cells infected 

with viruses can’t function properly and 

usually die. Many are eliminated by killer 

T cells. 
Different Types

of Vaccines 

Imagine that a new infectious disease emerges somewhere 

in the world and begins to spread around the globe. 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. 

Everyone agrees a vaccine against bacterium X is needed, 

but how would scientists go about creating one? First, 

researchers would carefully study bacterium X. 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. Other scientists would 

discover and study the toxin secreted by bacterium X. 

Once scientists had some basic information about 

bacterium X, they could begin designing vaccines that 

might work against it. Following are some of the options 

that researchers might pursue. They will give you an 

idea of the main types of vaccine strategies. (This imaginary 

new disease is caused by a bacterium, but scientists 

would use approaches similar to those outlined below 

to develop a vaccine against a new virus.) 

UNDERSTANDING VACCINES 21
 
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. 

Because a live, attenuated vaccine is the closest thing to 

a natural infection, these vaccines are good “teachers” 

of the immune system: 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. The remote 

possibility exists that the attenuated bacteria X in the 

vaccine could revert to a virulent form and cause 

disease. Also, not everyone can safely receive live, 

attenuated vaccines. For their own protection, people 

who have damaged or weakened immune systems— 

because they’ve undergone chemotherapy or have 

HIV, for example—cannot be given live vaccines. 

Another limitation is that live, attenuated vaccines 

usually need to be refrigerated to stay potent. 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. 

22 
Antigens 

Membrane 

Genetic 

material 

Live, attenuated vaccines use a weakened version of the microbe 

that has been changed to reduce or eliminate its potential to 

cause disease. This image shows the live microbe’s antigens, 

membrane, and genetic material. 

Viruses are simple microbes 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. This hostile environment 

takes the fight out of viruses: As they evolve to adapt to 

the new environment, they become weaker with respect 

to their natural host, human beings. 

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. This approach has been used to create a 

vaccine against the bacterium that causes cholera, Vibrio 

cholerae, although the live cholera vaccine has not been 

licensed in the United States. 

UNDERSTANDING VACCINES 23
 
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. 

This quality could be a drawback in areas where people 

don’t have regular access to health care and can’t get 

booster shots on time. 

Inactivated or killed vaccines contain microbes that have been 

inactivated with chemicals, heat, or radiation. The microbe’s 

antigens, membrane, and genetic material are still present. 

Antigens 

Membrane 

Genetic 

material 

24 
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 up 

the microbe, the chances of adverse reactions to the 

vaccine are lower. 

Subunit vaccines can contain anywhere from 1 to 20 or 

more antigens. Of course, identifying which antigens from 

bacterium X best stimulate the immune system would be 

a tricky, time-consuming process. Once scientists did 

that, however, they could make subunit vaccines against 

X in one of two ways. They could grow bacterium X 

in the laboratory, and then use chemicals to break the 

bacteria apart and gather the important antigens. 

Subunit vaccines contain just the antigens of the microbe that 

best stimulate the immune system. This image depicts antigens 

that have been separated from the rest of the microbe for use 

in a subunit vaccine. 

UNDERSTANDING VACCINES 25
 
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. The yeast then produced the 

antigens, which the scientists collected and purified for use 

in the vaccine. Research is also continuing on a recombinant 

subunit vaccine against hepatitis C virus. 

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. 

26 

Harmless toxoid molecules (artist’s representation) are used in 

toxoid vaccines to immunize and protect people against harmful 

toxins secreted by some microbes. 
Conjugate vaccines link antigens or 

toxoids to the polysaccharide or sugar 

molecules that certain bacteria use 

as a protective coating, thereby 

allowing the immune system to 

recognize and attack these “disguised” 

bacteria. A conjugate vaccine contains 

the molecules shown in the foreground. 

The bacterium, part of which is 

shown in the upper left background, 

is not part of the vaccine. 

Bacterium 

Polysaccharide 

molecule 

Toxoid 

Polysaccharide 

coating 

Linked toxoid and 

polysaccharide 

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 younger children can’t recognize 

or respond to them. Conjugate vaccines, a special type 

of subunit vaccine, get around this problem. 

UNDERSTANDING VACCINES 27 
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. 

28 
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 vaccinemaking factories, creating the antigens necessary to 

stimulate the immune system. A DNA vaccine against 

X would evoke a strong antibody response to the freefloating 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. 

DNA vaccines use a microbe’s genetic material, in particular, 

the genes that code for important antigens. The DNA in these 

vaccines is a circular form known as a plasmid. 

UNDERSTANDING VACCINES 29
 
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 DNA 

vaccines being tested in humans include those against the 

viruses that cause influenza and herpes as well as 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. 

Harmless 

microbial shell 

Genes from diseasecausing microbe 

30 

Recombinant vector vaccines use the harmless shell of one 

microbe to deliver genetic material of a disease-causing microbe. 

The genetic material contains the code for making vaccine antigen 

inside some of the body’s cells, using those cells as “factories.” 
In nature, viruses latch on to cells and inject their genetic 

material into them. (See “How Viruses Work” on page 

20.) 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 a harmful microbe, 

provoking an immune response. 

Researchers are working on both bacterial and viral-based 

recombinant vector vaccines for HIV, rabies, and measles. 

Many Vaccines Against 

Bacterium X? 

The search for a vaccine against bacterium X would 

likely result in several promising candidate vaccines. 

(Researchers working on an HIV vaccine, for example, 

have developed dozens of experimental vaccines at 

various stages of testing, including subunit vaccines, 

DNA vaccines, and recombinant vector vaccines.) But 

because of the rigorous research and testing each vaccine 

must go through, it would take years, possibly decades, 

before an X vaccine was approved for use in the United 

States. In “Making Safe Vaccines” on page 38, we’ll take 

a closer look at how vaccines are tested and regulated. 

UNDERSTANDING VACCINES 31
 
Vaccine Strategies 

One promising, but still experimental,
 

approach to vaccination is the prime-


boost strategy. This strategy involves two
 

vaccines. The first (frequently a DNA vaccine)
 

is given to prepare (“prime”) the immune system.
 

Next, this response is boosted through the administration of a
 

second vaccine (such as a viral-based vector vaccine). Several
 

prime-boost HIV vaccine candidates are being tested in humans. 


An infant’s immune system 

contains billions of circulating B 

and T cells capable of responding 

to millions of different antigens 

at once. 

Some vaccines come in combinations. You might be familiar with 

the DTP (diphtheria, tetanus, pertussis) and the MMR (measles, 

mumps, rubella) vaccines that children in the United States receive. 

Combination vaccines reduce visits to the doctor, saving time 

and money and sparing children extra needlesticks. Without 

combination vaccines, parents would have to bring their children 

in for each vaccination and all its boosters, and the chances 

would be greater that kids would miss their shots. Missed shots 

put children, as well as their communities, at risk. 

Some people have wondered whether combination vaccines 

might overwhelm or weaken a child’s immune system, but the 

immune system contains billions of circulating B and T cells 

capable of responding to millions of different antigens at once. 

Because the body constantly replenishes these cells, a healthy 

immune system cannot be “used up” or weakened by a vaccine. 

According to one published estimate, infants could easily 

handle 10,000 vaccines at once. 

For more sources of information on this topic, see “Vaccine 

Concerns, Myths, and Safety Issues on the Web” on page 42. 

32 
Adjuvants and Other 

Vaccine Ingredients 

UNDERSTANDING VACCINES 
33 

An adjuvant is an ingredient added to a vaccine to 

improve the immune response it produces. Currently, 

the only adjuvant licensed for human use in the 

United States is an “alum” adjuvant, which is 

composed of aluminum salts. Adjuvants do a variety 

of things; they can bind to the antigens in the vaccine, 

help keep antigens at the site of injection, and help 

deliver antigens to the lymph nodes, where immune 

responses to the antigens are initiated. The slowed 

release of antigens to tissue around the injection site 

and the improved delivery of antigens to the lymph 

nodes can produce a stronger antibody response than 

can the antigen alone. Alum adjuvants are also taken 

up by cells such as macrophages and help these cells 

better present antigens to lymphocytes. 

Scientists are trying to develop new and better 

adjuvants. One oil-based adjuvant, MF59, has been 

used in seasonal influenza vaccines already available 

in Europe. Other adjuvants under study include tiny 

spheres made of fatty molecules that carry the 

vaccine’s antigen, and inert nanobeads that can be 

coated with antigen. 

In addition to adjuvants, vaccines may contain 

antibiotics to prevent bacterial contamination during 

manufacturing, preservatives to keep multidose vials 

of vaccine sterile after they are opened, or stabilizers 

to maintain a vaccine’s potency at less-than-optimal 

temperatures. 
34 

Vaccine Type Disease 

Live, attenuated vaccines Measles, mumps, rubella, polio 

(Sabin vaccine), yellow fever 

Inactivated or Cholera, flu, hepatitis A, Japanese 

“killed” vaccines encephalitis, plague, polio (Salk 

vaccine), rabies 

Toxoid vaccine Diphtheria, tetanus 

Subunit vaccines Hepatitis B, pertussis, pneumonia 

caused by Streptococcus 

pneumoniae 

Conjugate vaccines Haemophilus influenzae type b, 

pneumonia caused by Streptococcus 

pneumoniae 

DNA vaccines In clinical testing 

Recombinant In clinical testing 

vector vaccines 

Some Vaccine Types and Diseases They Protect Against 
Advantages Disadvantages
 

Produce a strong immune response 

Often give lifelong immunity with 

one or two doses 

Remote possibility that the live 

microbe could mutate back to a 

virulent form 

Must be refrigerated to stay potent 

Safer and more stable than 

live vaccines 

Produce a weaker immune response 

than live vaccines 

Don’t require refrigeration: more 

easily stored and transported 

Usually require additional doses, or 

booster shots 

Teaches the immune system to fight 

off bacterial toxins 

Targeted to very specific parts of 

the microbe 

Fewer antigens, so lower chance of 

adverse reactions 

When developing a new vaccine, 

identifying the best antigens can 

be difficult and time consuming 

Allow infant immune systems to 

recognize certain bacteria 

Produce a strong antibody and 

cellular immune response 

Still in experimental stages 

Relatively easy and inexpensive 

to produce 

Closely mimic a natural infection, 

stimulating a strong immune response 

Still in experimental stages 

UNDERSTANDING VACCINES 35 
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 diarrhea, and have 

created a food-based vaccine containing a protein from 

respiratory syncytial virus, which can cause serious respiratory 

illness, especially in young 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’ 

diarrhea, tetanus, anthrax, and seasonal flu. 

36 
Future vaccines may be squirted into the nose, 

worn as a patch, or eaten at the dinner table. 

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 your body, which may produce a better 

immune response. (For more on the vaccine approval process, 

see “Making Safe Vaccines,” page 38.) 

Nasal flu vaccine eliminates the dreaded needle, but people 

must still get the vaccine every year because the circulating 

influenza virus strains change. The annual flu shot may 

become a thing of the past, however, if researchers working on 

a so-called universal flu vaccine succeed. To make a universal 

flu vaccine that would work for more than 1 year, scientists 

incorporate parts of the flu virus that do not change very much. 

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 against some 

cancers, HIV, certain allergies, and multiple sclerosis. 

UNDERSTANDING VACCINES 37
 
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, people will 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. That is one reason that the bar 

of vaccine safety is set so high. 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. Today, 

with improved technology and research methods, the length 

of time from basic research to availability of a licensed 

vaccine can sometimes be reduced. If a vaccine is approved, 

FDA and other government agencies continue to monitor it 

for safety. Following are some of the key measures taken to 

ensure vaccines are safe. 

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. 

38 
This vaccine researcher 

uses a multi-channel 

pipetter to quickly 

prepare many biological 

samples for analysis. 

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. (See “Volunteering 

for a Clinical Study,” page 41.) 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. 

UNDERSTANDING VACCINES 39
 
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. 

Scientists cannot, of course, deliberately expose human 

volunteers to certain microbes, such as Ebola or anthrax, 

to determine how well a vaccine works. 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, and show the results of safety and purity tests 

on batches of the vaccine intended for public use. 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. 

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. 

40 
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 for as 

long as the vaccine is made. 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. 

Volunteering for a 

Clinical Study 

UNDERSTANDING VACCINES 
41 

Clinical trials rely entirely on 

volunteers—people who 

contribute their time and energy

for the advancement of science 

and improved health care for 

all. Tens of thousands of 

volunteers of all ages and 

walks of life have participated 

in these trials. 

Typically, a volunteer in a 

vaccine study agrees to be 

given the vaccine (or a lookalike placebo), visits a clinic 

frequently for evaluation, 

undergoes medical tests, and 

provides blood samples that 

researchers will use to assess 

the vaccine. Because no one 

knows yet how well the vaccine 

works, participants should not 

expect the experimental vaccine 

to protect them against disease. 

Volunteers are fully informed 

about how the study will be 

conducted, its potential risks 

and benefits, and measures 

taken to ensure their safety and 

privacy. To find out more about 

government clinical studies, 

visit www.clinicaltrials.gov. 
42 

AIDSinfo

A service of the U.S. Department 

of Health and Human Services 

aidsinfo.nih.gov 

800–448–0440 

Centers for Disease Control 

and Prevention 

National Immunization Program 

www.cdc.gov/nip 

800–232–2522 

Immunization Safety Review 

Committee of the Institute 

of Medicine 

www.iom.edu/imsafety 

202–334–1342 

Institute for Vaccine Safety 

Johns Hopkins Bloomberg 

School of Public Health 

www.vaccinesafety.edu 

National Network for 

Immunization Information 

www.immunizationinfo.org 

409–772–0199 

National Partnership 

for Immunization 

www.partnersforimmunization.org 

703–836–6110 

Vaccine Education Center at The 

Children’s Hospital of Philadelphia 

www.vaccine.chop.edu 

215–590–9990 

Vaccine Concerns, Myths, and Safety 

Issues on the Web 

Now that vaccines have virtually eliminated many once-feared 

diseases, the possibility of vaccine side effects or adverse reactions 

loom larger in some people’s minds than the diseases that vaccines 

prevent. Most parents today have never seen a case of diphtheria 

or measles, and some wonder why their children must receive so 

many shots. Rumors and misinformation about vaccine safety 

abound. For example, many parents are concerned that multiple 

vaccines may weaken or overwhelm an infant’s immune system 

or that certain vaccines may cause autism, multiple sclerosis, 

or diabetes. 

For information about vaccine concerns, myths, and safety issues, 

try the following sources. 
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 (VTEUs). These 

UNDERSTANDING VACCINES 43
 
testing sites are based at university medical research 

centers, public health departments, and community 

clinics across the country. The network can rapidly 

recruit volunteers for clinical studies, and it played a 

major role in the studies that led to the licensing of 

vaccines for Hib and for a new subunit pertussis 

vaccine. 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), a network of testing centers at universities in 

the United States devoted exclusively to HIV vaccines. 

In 1999, NIAID built upon AVEG by creating the HIV 

Vaccine Trials Network (HVTN), a collaboration of 

investigators in the United States and abroad that tests 

candidate HIV vaccines in clinical trials. The HVTN 

includes sites in Africa, Asia, South America, and the 

Caribbean. 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. 

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. Scientists at the center conduct basic research on 

microbes and the immune system’s response to them, 

44 
design candidate vaccines, and with their collaborators, 

test the most promising vaccines in preclinical and 

clinical trials. 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. Vaccines 

against such emerging microbes must be safe, easy to 

administer, and fast-acting—even to the point of 

providing immunity shortly after exposure to the 

microbe. 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. Among their 

efforts, CHAVI scientists are seeking a better 

understanding of the earliest events in the immune 

UNDERSTANDING VACCINES 45
 
system’s response to HIV infection; identifying which 

immune reactions give the best indications that a 

candidate vaccine is eliciting a protective response; and 

testing new HIV vaccines in early phase clinical trials. 

In recent years, researchers have increased their 

understanding of the immune system and how it fights 

off harmful microbes. 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. 

46 
More Information
 

National Institute of Allergy and Infectious Diseases 

National Institutes of Health 

6610 Rockledge Drive, MSC 6612 

Bethesda, MD 20892-6612 

301–496–5717 

www.niaid.nih.gov 

Dale and Betty Bumpers Vaccine Research Center 

National Institutes of Health 

40 Convent Drive 

Bethesda, MD 20892 

www.niaid.nih.gov/vrc 

National Library of Medicine 

MedlinePlus 

8600 Rockville Pike 

Bethesda, MD 20894 

1–888–FIND–NLM (1–888–346–3656) or 301–594–5983 

www.medlineplus.gov 

Centers for Disease Control and Prevention 

1600 Clifton Road 

Atlanta, GA 30333 

1–800–311–3435 or 404–639–3534 

www.cdc.gov 

Food and Drug Administration 

5600 Fishers Lane 

Rockville MD 20857-0001 

1–888–INFO–FDA (1–888–463–6332) 

www.fda.gov 

World Health Organization 

Avenue Appia 20 

1211 Geneva 27 

Switzerland 

41–22–791–21–11 

www.who.int 

UNDERSTANDING VACCINES 47 
Glossary
 

adjuvant—a substance sometimes included in a 

vaccine formulation to enhance the immune-stimulating 

properties of the vaccine. 

antibody—a molecule produced by a B cell in response 

to an antigen. When an antibody attaches to an antigen, 

it helps destroy the microbe bearing the antigen. 

antigen—a molecule on a microbe that identifies it 

as foreign to the immune system and stimulates the 

immune system to attack it. 

artificially acquired immunity—immunity provided 

by vaccines, as opposed to naturally acquired immunity, 

which is acquired from exposure to a disease-causing 

organism. 

attenuation—the weakening of a microbe so that it can 

be used in a live vaccine. 

B cell or B lymphocyte—a white blood cell, crucial to 

the immune defenses. B cells come from bone marrow 

and develop into blood cells called plasma cells, which 

are the source of antibodies. 

bacteria—microscopic organisms composed of a 

single cell and lacking a defined nucleus and membraneenclosed internal compartments. 

booster shot—supplementary dose of a vaccine, 

usually smaller than the first dose, that is given to 

maintain immunity. 

48 
cell-mediated immune response (also called cellular 

immune response)—immune protection provided by 

the direct action of immune cells (as distinct from that 

provided by molecules such as antibodies). 

clinical trial—an experiment that tests the safety and 

effectiveness of a vaccine or drug in humans. 

complement protein—a molecule that circulates in 

the blood whose actions “complement” the work of 

antibodies. Complement proteins destroy antibodycoated microbes. 

conjugate vaccine—a vaccine in which proteins that are 

easily recognizable to the immune system are linked to 

the molecules that form the outer coat of disease-causing 

bacteria to promote an immune response. Conjugate 

vaccines are designed primarily for very young children 

because their immune systems cannot recognize the 

outer coats of certain bacteria. 

contagious—able to transmit disease to other people. 

cytotoxic T cells or killer T cells—a subset of T cells 

that destroy body cells infected by viruses or bacteria. 

dendritic cell—immune cell with threadlike tentacles 

called dendrites used to enmesh antigen, which it 

presents to T cells. 

UNDERSTANDING VACCINES 49
 
DNA vaccine or naked DNA vaccine—a vaccine that 

uses a microbe’s genetic material, rather than the whole 

organism or its parts, to stimulate an immune response. 

edible vaccines—foods genetically engineered to 

produce antigens to specific microbes and safely trigger 

an immune response to them. 

efficacy—in vaccine research, the ability of a vaccine 

to produce a desired clinical effect, such as protection 

against a specific infection, at the optimal dosage and 

schedule in a given population. 

formalin—a solution of water and formaldehyde, 

used in toxoid vaccines to inactivate bacterial toxins. 

gene—a unit of genetic material (DNA). Genes carry 

directions a cell uses to perform a specific function. 

genetic material—molecules of DNA (deoxyribonucleic 

acid) or RNA (ribonucleic acid) that carry the directions 

that cells or viruses use to perform a specific function, 

such as making a particular protein molecule. 

genomes—all of an organism’s genetic material. A genome 

is organized into specific functional units called genes. 

Haemophilus influenzae type b (Hib)—a bacterium 

found in the respiratory tract that causes acute 

respiratory infections, including pneumonia, and other 

diseases such as meningitis. 

50 
helper T cells—a subset of T cells that function as 

messengers. They are essential for turning on antibody 

production, activating cytotoxic T cells, and initiating 

many other immune functions. 

herd immunity or community immunity—the 

resistance to a particular disease gained by a community 

when a critical number of people are vaccinated against 

that disease. 

HIV—human immunodeficiency virus, the virus that 

causes AIDS. 

humoral immune response or antibody response— 

immune protection provided by B cells, which secrete 

antibodies in response to antigen (as distinct from that 

provided by the direct action of immune cells, or the 

cellular immune response). 

immune—have a high degree of resistance to or 

protection from a disease. 

immune system—a collection of specialized cells and 

organs that protect the body against infectious diseases. 

inactivated vaccine or killed vaccine—a vaccine made 

from a whole virus or bacteria inactivated with chemicals 

or heat. 

live, attenuated vaccine—a vaccine made from microbes 

that have been weakened in the laboratory so that they 

can’t cause disease. (See attenuation.) 

UNDERSTANDING VACCINES 51
 
lymph node—a small bean-shaped organ of the immune 

system, distributed widely throughout the body and 

linked by lymphatic vessels. Lymph nodes are gathering 

sites of B, T, and other immune cells. 

lymphocyte—a white blood cell central to the immune 

system’s response to foreign microbes. B cells and T cells 

are lymphocytes. 

macrophage—a large and versatile immune cell that 

devours and kills invading microbes and other intruders. 

Macrophages stimulate other immune cells by presenting 

them with small pieces of the invaders. 

memory cells—a subset of T cells and B cells that have 

been exposed to antigens and can then respond more 

readily and rapidly when the immune system encounters 

the same antigens again. 

microbe—a microscopic organism. Microbes include 

bacteria, viruses, fungi, and single-celled plants and 

animals. 

molecule—a building block of a cell. Some examples are 

proteins, fats, and carbohydrates. 

mutate—to change a gene or unit of hereditary material 

that results in a new inheritable characteristic. 

naturally acquired immunity—immunity produced by 

antibodies passed from mother to fetus (passive), or by 

the body’s own antibody and cellular immune response 

to a disease-causing organism (active). 

52 
organism—an individual living thing. 

passive immunity—immunity acquired through transfer 

of antibody or lymphocytes from an immune donor. 

pertussis or whooping cough—a respiratory infection 

caused by the toxic bacterium Bordetella pertussis. The 

wracking coughs characteristic of this disease are 

sometimes so intense the victims, usually infants, vomit 

or turn blue from lack of air. 

placebo—an inactive substance administered to some 

clinical trial participants. Other participants receive the 

agent being evaluated, which provides a basis for 

comparing the agent’s effects. 

plasma cell—a cell produced by a dividing B cell that is 

entirely devoted to producing and secreting antibodies. 

polysaccharide—a long, chain-like molecule made up of 

a linked sugar molecule. The outer coats of some bacteria 

are made of polysaccharides. 

preclinical testing—required laboratory testing of a 

vaccine before it can be given to people in clinical trials. 

Preclinical testing is done in cell cultures and in animals. 

recombinant DNA technology—the technique by which 

genetic material from one organism is inserted into a 

foreign cell or another organism in order to mass-produce 

the protein encoded by the inserted genes. 

UNDERSTANDING VACCINES 53
 
recombinant subunit vaccine—a vaccine made using 

recombinant DNA technology to engineer the antigen 

molecules of the particular microbe. (See subunit vaccine.) 

recombinant vector vaccine—a vaccine that uses 

modified viruses or bacteria to deliver genes that code 

for microbial antigens to cells of the body. 

rubella or German measles—a viral disease often 

affecting children and spread through the air by coughs 

or sneezes. Symptoms include a characteristic rash, 

low-grade fever, aching joints, runny nose, and reddened 

eyes. If a pregnant woman gets rubella during her first 

3 months of pregnancy, her baby is at risk of having 

serious birth defects or dying. 

subunit vaccine—a vaccine that uses one or more 

components of a disease-causing organism, rather than 

the whole, to stimulate an immune response. 

T cell or T lymphocyte—a white blood cell that directs 

or participates in immune defenses. (See cytotoxic T cells 

and helper T cells.) 

tissue—a group of similar cells joined to perform the 

same function. 

toxin—agent produced by plants and bacteria, normally 

very damaging to cells. 

toxoid or inactivated toxin—a toxin, such as those 

produced by certain bacteria, that has been treated by 

chemical means, heat, or irradiation and is no longer 

capable of causing disease. 

54 
toxoid vaccine—a vaccine containing a toxoid, used to 

protect against toxins produced by certain bacteria. 

vector—in vaccine technology, a bacterium or virus that 

cannot cause disease in humans and is used in genetically 

engineered vaccines to transport genes coding for 

antigens into the body to induce an immune response. 

virulent—toxic, causing disease. 

virus—a very small microbe that does not consist of 

cells but is made up of a small amount of genetic material 

surrounded by a membrane or protein shell. Viruses 

cannot reproduce by themselves. To reproduce, viruses 

must infect a cell and use the cell’s resources and molecular 

machinery to make more viruses. 
U.S. DEPARTMENT OF HEALTH AND HUMAN SERVI

National Institutes of Health 

National Institute of Allergy and Infectious Diseases 

NIH Publication No. 08-4219 

January 2008 

CES 

www.niaid.nih.gov