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Vaccines and your health

Excerpted from The Truth About Your Immune System, a Special Health Report from Harvard Health Publications

To build immunity, you must first be exposed to germs. But why not stop the germs in their tracks before they have a chance to multiply and make you ill? This is precisely what vaccination does. It rallies the forces of the immune system before the battle has a chance to begin. By so doing, vaccination confers immunity against disease.

How vaccines work

The vaccination process mimics what would happen naturally when a potentially harmful bacterium or virus breaches the body’s defenses, but with one essential difference — there’s no harmful germ involved. Instead, the vaccine contains a recognizable but defanged version of the pathogen. When you’re vaccinated, your innate immune system is fooled into thinking that a pathogen has gotten in.

A signal goes to the T cells and B cells of the adaptive immune system, which quickly launch an attack as if a real pathogen were invading. Finally, the response winds down, leaving in place the long-lived memory T cells and B cells (see “Memory: Long-term protection”) fully briefed for future encounters. Most vaccines don’t prevent pathogens from entering your body; they just make sure your immune system blocks them quickly and keeps them from making you sick.

How does vaccination accomplish its goal? Most current vaccines work to mobilize antibodies, proteins generated by a type of B cell known as a plasma cell. Consequently, most of today’s effective vaccines work by stimulating antibody-producing memory B cells. Antibodies are homing devices of the immune system. They can lock on to the receptors of recognized bad guys and block them from attacking your healthy cells.

What’s in a name? Strictly speaking, vaccination is the giving of vaccines to prevent disease. Immunization means acquiring immunity against disease, that is, protection against getting sick. Successful vaccination results in immunization. Sometimes these distinctions are fuzzy; you may see vaccination and immunization used synonymously. The term inoculation is also commonly used to mean vaccination.

Antibody action

Antibodies, which behave like guided missiles, operate outside of cells to block pathogens from attaching to healthy cells. Traveling in the blood, they are able to quickly reach invading pathogens and their toxins, wherever they may be.

Antibodies are highly specific. Every antibody circulating in the bloodstream looks for a particular molecule on the surface of the invading germ. Once an antibody sees what it is looking for — bingo! The missile locks on to its target.

When antibodies attach themselves to target molecules on the surface of a pathogen, this blocks the pathogen from attaching itself to your healthy cells. Not surprisingly, the design of most of today’s vaccines relies on applying this neutralizing capability of antibodies to strike out pathogens so they can’t get to your cells.

Antibodies have several other strategies as well. They chemically “paint” germs so they are recognizable to and can be destroyed by the phagocytes — the gobblers of the innate immune system. This coordinated effort of the adaptive immune system (antibodies) and the innate immune system (phagocytes) provides a powerful defense against attack. Antibodies also work with other proteins in the blood to punch “holes” in some pathogens, thereby killing them. The same proteins that kill pathogens help activate the attack of the immune system.

Vaccination: A success story

Virtually everyone reading this report has been vaccinated. Apart from the forgotten vaccinations of infancy, many of us get annual flu shots, tetanus boosters, and travel shots. Nowadays “shots” are so ubiquitous that most of the time you never think twice about them. It’s easy to forget this protection wasn’t always so readily available.

Without a doubt, vaccination is a stupendous success story in the war against disease (see Table 1). Contagious illnesses that once ravaged populations have been controlled and, in some instances, eliminated or nearly eliminated. Smallpox, for instance, was officially eradicated in 1977, and polio is close to eradication — down from an estimated 350,000 cases worldwide in 1988 to 1,951 in 2005. In 2006 there were polio outbreaks in only four countries compared with 125 in 1988.

Table 1: Some common vaccine-preventable diseases
Disease	Infectious agent	Who should be vaccinated?
Bacterial meningitis	Neisseria meningitidis	children; unvaccinated high-school and college students
Bacterial pneumonia	Streptococcus pneumoniae	adults over 65; children at risk ages 2–5
Chickenpox	varicella-zoster virus	children and adults who have not been vaccinated or who have not had the disease
Diphtheria	Corynebacterium diphtheriae	children (usually given in combination with the tetanus and pertussis vaccines)
Ear infections; meningitis	Haemophilus influenzae	children under 5
Genital warts; cervical cancer	human papillomavirus	preadolescent girls; sexually active women
Hepatitis A	hepatitis A virus (HAV)	children and adults at risk of exposure to HAV; those at serious risk of illness from HAV
Hepatitis B	hepatitis B virus (HBV)	children 18 and younger; people at risk
Influenza A and B	influenza virus	children 6–23 months; adults over 50; people in residential care facilities; people who are immunocompromised
Measles	measles virus	children ages 1 and up
Mumps	mumps virus	children
Pertussis (whooping cough)	Bordetella pertussis	children
Polio	polio virus	all children
Rubella	rubella virus	children 12–15 months
Severe diarrhea	rotavirus	children
Shingles	varicella-zoster virus	adults 60 and older
Tetanus	Clostridium tetani	children; adults require booster every 10 years
No vaccines are available for malaria, hepatitis C, or HIV/AIDS.

As the scientists of yesteryear slowly came to understand that some people resisted infectious diseases while others succumbed and that steps could be taken to influence the outcome, a new scientific discipline was born — immunology.

The first vaccine was developed by Edward Jenner (1749–1823), an English country physician. He observed that milkmaids rarely contracted smallpox, although the disease was rampant, accounting for about one-third of all childhood deaths as well as scarring in one out of three adults. Jenner suspected that the milkmaids may have been protected by their exposure to an infection called cowpox, which is not harmful to humans. In 1796 Jenner conducted a groundbreaking experiment. He took fluid from a cowpox blister on the hand of a milkmaid and rubbed it into scratches on the arm of an 8-year-old boy who had not had cowpox or smallpox. This inoculated the boy with the cowpox virus. Six weeks later, Jenner injected the boy with fluid from a smallpox blister. The boy didn’t become sick. Jenner had discovered that a harmless foreign organism could provide protection against a closely related but more deadly organism. Because of the cow connection — vaccinus is the Latin word for “of cows,” from vacca meaning “cow” — Jenner’s procedure came to be known as “vaccination,” a term subsequently applied to other types of inoculations, cow-related or not. Despite Jenner’s breakthrough discovery, many years passed before Louis Pasteur developed the next vaccines, for rabies, anthrax, and cholera.

A truism of scientific progress: Discoveries don’t happen in an intellectual vacuum. So it was with Jenner. People of 18th-century England already knew that they could be protected against smallpox by introducing fluid from smallpox blisters into scratches on their skin. While this widely practiced approach, which had come from Turkey, afforded a degree of protection, it also involved a risk of developing the disease — and dying from it. Jenner’s distinctive contribution was demonstrating that harmless cowpox, which carried no risk of smallpox, could provide protection against the scourge of the times.

Types of vaccines

Over the course of vaccine history, scientists have devised several types of vaccines.

Live attenuated vaccines. These vaccines contain a live microbe that is weakened in such a way that it can no longer cause disease. Live attenuated vaccines elicit a strong immune response, involving both memory B cells and memory T cells, and can confer lifelong immunity after as few as one or two doses (see Figure 5).

There are drawbacks, however. The attenuated form of the pathogen in the vaccine could mutate (just as any other living organism can mutate) and regain the ability to cause the disease. This risk is extremely small in healthy people but greater in people with already compromised immune systems. For this reason, people with cancer or those infected with HIV shouldn’t receive live attenuated vaccines. Another drawback of live attenuated vaccines is that they must be stored in refrigerators to keep them fresh and alive. This requirement is not a big concern in developed countries, but it makes vaccines of this type, such as the current measles vaccine, impractical in many developing countries where immunization is desperately needed.

Inactivated or “killed” vaccines. These are the most common type of vaccine today. They are made with pieces of a virus that has been killed with heat, chemicals, or radiation. Consequently, inactivated (“killed”) vaccines don’t have the risk of mutating and reverting back to their virulent form. They work by stimulating B cells to produce antibodies. And they typically don’t require refrigeration. But inactivated vaccines also have some drawbacks. The major one is they often are not as potent as live attenuated vaccines because they only stimulate the production of antibodies and don’t engage other aspects of the adaptive immune system, such as the memory T cells. So to maintain immunity, you need periodic booster shots (see Figure 5).

Figure 5: Live vs. killed vaccine Live vaccine. The first injection allows the virus to multiply rapidly, prompting a full-scale immune response with antibody production and a T cell response. Pros and cons: Only one injection is needed but there is a minute risk of developing the disease. Killed vaccine. A killed virus can’t multiply and the antibody response is limited. Two further injections at later dates ensure sufficient antibody production. Pros and cons: There is no risk of developing the disease but three injections are needed.

Subunit vaccines. Whereas some vaccines use the whole microbe, subunit vaccines use only those parts of the microbe that stimulate the immune system well, namely the antigens. By containing only what is needed for an immune response and not all the other parts of the microbe, subunit vaccines tend to cause fewer adverse reactions.

Toxoid vaccines. With some bacterial diseases, such as diphtheria and tetanus, the problem is not the bacteria themselves but rather the toxins they produce, which enter and poison cells. Therefore, these vaccines contain inactivated toxins known as toxoids. Toxoid vaccines stimulate antibody production. When a person is infected, these antibodies can block the toxins from getting into cells.

Vaccinating infants and children

Usually, immunity refers to active immunity, in which your body uses your immune system’s weapons to respond to an attack. However, there is another form of immunity called passive immunity. This occurs when the immunity of one individual, in the form of antibodies, is transferred to another individual who has not been exposed to the antigen.

The classic example of passive immunity is the protection a mother confers upon the child she is carrying in her womb when her antibodies pass across the placenta to the fetus. Thanks to this transfer of mom’s antibodies, the fetus becomes the passive recipient of mom’s immunity. Since babies are born without an adequate immune system of their own, they still need mom’s immune protection. During the first day or so of life, breast-fed newborns ingest more of mom’s antibodies via colostrum, the antibody-rich secretion that precedes the flow of breast milk. However, these received maternal antibodies wane over the first months of life, before the infant’s own immune system is sufficiently developed to beat back infectious diseases by itself. Hence infectious diseases are especially dangerous for the young.

Early vaccination protects children when they are especially vulnerable to potentially lethal diseases. And early vaccination has done more than anything else to lower the rate of childhood deaths worldwide.

One for all and all for one: Herd immunity Vaccination protects individuals from disease, but its impact is more far-reaching. Vaccination also benefits an entire community. When you are infected, your vaccine-primed immune system revs up to speed and stops you from becoming contagious — or at least shortens the time you are contagious — minimizing your opportunity to infect others. Likewise, if everyone around you has been vaccinated, you, by definition, are more likely to be protected from infection. And there comes a point when enough members of a community have vaccine protection that everyone in that community, including even the unvaccinated, is less likely to get sick. This phenomenon is called herd immunity or community immunity. The phenomenon can work in reverse. If enough people forgo vaccination, the entire community is put at risk. In 1974, bowing to public opinion regarding the safety of the pertussis vaccine and lulled into complacency because there had been no pertussis fatalities the previous year, the Japanese government suspended its pertussis vaccination program. A pertussis epidemic broke out five years later in which 13,000 people fell ill and 41 died. Similarly, a 1989 outbreak of measles, stemming from low vaccination rates, caused 136 deaths out of 55,000 cases in the United States. The antivaccine movement in the United States and other developed countries is a major concern (see “Do vaccines pose health risks?”). Once sufficient numbers of children are left unvaccinated, diseases once thought to be under control will come back. Sadly, the very children who remained unvaccinated because of their parents’ opposition will be the most at risk as herd immunity begins to wane.

Do vaccines pose health risks?

Impressive though the documented benefits are, certain vaccines pose some risks. The pertussis (whooping cough) vaccine, for example, can very rarely cause serious problems. According to the Centers for Disease Control and Prevention (CDC), the risk of harm or death is extremely low. A serious reaction occurs in fewer than one in a million people who receive the combined diphtheria, tetanus, and pertussis vaccine (DTaP). The current combined DTaP vaccine is even safer than the earlier DTP vaccine. Moreover, with the combined DTaP vaccine, the incidence of long-term seizures and permanent brain damage is so rare it’s hard to tell whether the vaccine is the culprit.

There have been debates about the safety of combining several vaccines into a single shot. The combined measles, mumps, and rubella (MMR) vaccine has been the focus of most concern. But there is no scientific reason not to give a child the combined MMR as recommended by the CDC. According to a 2002 CDC report titled “General Recommendations on Immunization,” the rates for a vaccine reverting to a virulent form and having any adverse reactions were the same for combined vaccines as they were for singly administered vaccines. The major benefits of simultaneous administration are fewer shots for the child and knowing that a child has received all the requisite shots at the right age.

Another anxiety arose from the findings of a study published in 1998 suggesting a connection between the combined MMR vaccination and autism. The study understandably created a storm at the time. However, in 2003, the CDC stated that many carefully designed studies have not been able to find a causative link between the MMR vaccine and autism, and in 2004, scientists involved in the original study retracted their conclusions. Also in 2004, the Institute of Medicine (IOM) of the National Academies published a report, “Immunization Safety Review: Vaccines and Autism,” in which the IOM concluded that the body of epidemiological evidence could not find a link between the MMR vaccine and autism. Nor have studies been able to find a link between MMR and inflammatory bowel disease, another source of parental concern.

It’s important to keep in mind that although measles deaths have fallen by 60% since 1999 thanks to vaccination worldwide — from 873,000 in 1999 to 345,000 in 2005 — measles can still be life-threatening. Parents who opt out of the combination MMR vaccine for their children because of what they view as vaccine safety concerns are putting their children at greater risk of a potentially very serious disease. A report from the United Kingdom noted that measles is on the rise again. This is cause for alarm because in 2000 the World Health Organization estimated 7,000 deaths attributable to measles in Europe.

Immunization is also important for some adults. The CDC recommends an annual inactivated influenza vaccine, particularly for anyone over age 50, residents of long-term care facilities, people with chronic health problems, people with weakened immune systems, pregnant women who will be past their third month during flu season, and medical professionals and family members who will be in close contact with anyone who is an influenza risk. The message is clear: Don’t be complacent. Flu is a highly infectious disease of the lungs that can lead to pneumonia. Each year flu sends about 114,000 U.S. residents to the hospital and kills an average of 30,000. Flu is not merely a bad cold!

Table 2: Vaccines by type
Vaccine type	Disease
Live attenuated vaccines	Measles, mumps, rubella, polio (Sabin vaccine), severe diarrhea, influenza (intranasal vaccine), chickenpox, and shingles
Inactivated or “killed” vaccines	Influenza, hepatitis A, Japanese encephalitis, polio (Salk vaccine), rabies
Subunit vaccines	Diphtheria, genital warts and cervical cancer (prevention), hepatitis B, meningococcal disease, pertussis, pneumococcal disease, tetanus

Newer vaccine players

Because vaccines are typically — but not always — administered to healthy people, the FDA is understandably cautious and very demanding before it will license a new vaccine. But it has licensed several newer vaccines against important diseases: the human papillomavirus (HPV), varicella-zoster virus, and childhood hepatitis A vaccines, as well as a second meningococcal vaccine. The FDA has also approved a preliminary bird flu vaccine to keep stockpiled in case of a bird flu pandemic.

The HPV vaccine, licensed in June 2006, has received a great deal of press. The vaccine is recommended for females beginning at 11 or 12 years of age, although it can be administered to girls as young as age 9. This vaccine offers protection against the four most common HPV strains that are responsible for 70% of cervical cancers and 90% of genital warts. Ideally, girls should receive the vaccine before they become sexually active. Studies that included 11,000 girls and women, ages 9 to 26, showed that the vaccine was safe and had no serious side effects. However, no vaccine is 100% protective, so females should continue to have regular Pap smears to screen for cervical cancer. Although males are also carriers of HPV, currently there are no recommendations to vaccinate boys or men because they cannot get cervical cancer.

The FDA also licensed the varicella-zoster virus vaccine for shingles in 2006. (Shingles is caused by the chickenpox virus, which remains in the body after an initial chickenpox infection and may emerge many years later to cause the painful condition known as shingles.) The CDC now recommends the varicella-zoster virus vaccine for people over age 60 to prevent shingles and to reduce shingles-associated pain.

Although an adult vaccine for hepatitis A was introduced in 1995–96, a vaccine suitable for children ages 12 to 23 months was not licensed until 2005. A further addition to the existing vaccine arsenal is the meningococcal conjugate vaccine (MCV4), which was licensed in 2005 to combat bacterial meningitis.

The bird flu vaccine will not be available to the public except in case of a pandemic of bird flu. Although the number of human deaths attributable to bird influenza strains has been low thus far, there remains the very real fear of a pandemic should the viral strains mutate sufficiently to pass easily from person to person. Worldwide, millions of poultry have been destroyed in an attempt to stem the spread of the disease. The vaccine is only moderately effective against the most dangerous strain of bird flu, known as H5N1. It is considered a stopgap measure until an actual large-scale outbreak occurs and scientists can develop a vaccine that is more specific to the strain of bird flu that causes it.

Influenza, the disguise artist The flu provides an excellent example of what is called antigenic variation. As the flu virus replicates, it mutates. Mutation follows mutation until the surface of the virus at large in the community looks so different from the original virus that a person’s immune system no longer recognizes it as being the same microbe that it encountered in the past. This gives the now-mutated flu virus an opportunity to infect the same population again. By significantly changing its appearance, the new strain of virus is able to sneak past the immune system’s surveillance mechanisms. Because this process happens relatively gradually, it’s called antigenic drift. The flu virus demonstrates the difficulty of accounting for antigenic drift when creating a vaccine. At any time, there are several active flu strains in the world. Every year, to protect the U.S. population, the CDC reevaluates the three strains of flu virus in the U.S. flu vaccine and, if necessary, changes the vaccine recipe. The accuracy of the recipe determines how effective that year’s vaccine will be. In some years the recipe isn’t as accurate as in others. In those years, the vaccine doesn’t protect as well, and more people get sick with the flu. The flu virus can defeat the immune system in a far more dramatic manner as well. If two different viruses from two different hosts, such as from humans and ducks, get into the same cell, the result is a hybrid virus with completely novel antigens. This can spread like a windblown forest fire through the world’s human population, which has little or no immune resistance to the new form. This scenario, called antigenic shift, can give rise to a pandemic. Examples of antigenic shift include the periodic outbreaks of Asian flu and Hong Kong flu during the 20th century and, more recently, SARS and bird flu in humans.

 

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