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Vaccines for Teenagers

Vaccines for Teenagers

Parents keep babies and toddlers on track with recommended immunizations by making frequent well-child visits to the pediatrician’s office. Adolescents and teenagers also need vaccines, but they tend not to visit the doctor as often as young children do. Not surprisingly, many teenagers haven’t received all of the vaccines recommended to protect them from potentially life-threatening diseases.

Data from the U.S. Centers for Disease Control and Prevention show that only about half of all teenagers have received the meningococcal vaccine, which protects against bacterial infections that may lead to amputation of infected limbs and death. In 2014, only 39.7% of teenage girls have received the complete three-dose series of the human papillomavirus vaccine (a vaccine that prevents infection with several viruses that cause cervical cancer). About 47% of all U.S. adolescents received the recommended influenza vaccine during the 2014-2015 influenza season. Clearly, large numbers of teenagers remain vulnerable to these diseases.

Apart from protecting themselves, teenagers (and their parents) should consider the benefits of vaccination to the family and community. In most cases, a person who is successfully vaccinated against a disease cannot spread that disease to other people. High rates of vaccination help protect those around us who cannot be immunized for health reasons (such as illness, age, or allergy). This principle is known as herd immunity, or community immunity.

Following are vaccines typically recommended for the pre-teen and teenage years.

Tdap Immunization

The U.S. Advisory Committee on Immunization Practices (ACIP) recommends a booster dose of the tetanus, diphtheria, acellular pertussis (Tdap) vaccine at age 11-12. (Most adolescents will have received five previous doses of a related vaccine by age 4-6.) The immunization provides continuing protection from tetanus, diphtheria, and pertussis.

Tetanus is a disease of the central nervous system caused by a toxin secreted by the bacterium Clostridium tetani. The early symptoms of the disease are lockjaw (the most recognizable of its physical effects), stiffness, and problems swallowing. Later symptoms include severe muscle spasms, seizure-like activity, and severe nervous system disorders. Between 10% and 25% of tetanus cases result in death.

Tetanus is not passed from person to person. Instead, tetanus is transmitted when Clostridium tetani bacteria enter injured skin and underlying tissues. Surprisingly, tetanus infection is more likely from a minor wound than a major one, but this is because severe wounds are more likely to be properly treated and cleaned.

Diphtheria is an uncommon disease that once was a major killer of children. It is caused by the bacterium Corynebacterium diphtheria. Early symptoms of diphtheria are similar to those of a common cold. They include sore throat, loss of appetite, and fever. As the disease progresses, the most notable feature of diphtheria infection may emerge: a thick gray substance called a pseudomembrane may spread over the nasal tissues, tonsils, larynx, and/or pharynx. The pseudomembrane sticks to tissues and may obstruct breathing.

Pertussis, also known as whooping cough, is an extremely contagious disease caused by the Bordetella pertussis bacterium. These bacteria produce toxins that paralyze parts of respiratory cells, leading to inflammation in the respiratory tract.

Early symptoms include runny nose, sneezing, a mild cough, and fever. However, the cough gradually becomes more severe. Eventually the patient experiences bouts of rapid coughing often followed by the “whooping” sound that gives the disease its common name as they try to inhale. While the coughing fit is occurring, the patient may turn blue. Coughing may be severe enough to cause broken ribs, and coughing spells may last for weeks or months. Newborns, who are too young to be immunized, are especially vulnerable to severe complications or death from whooping cough. Family members of newborns are especially encouraged to be immunized in order to protect the newborn.

Meningococcal Vaccine

The ACIP recommends a first dose of the quadrivalent meningococcal conjugate vaccine at 11-12 years old. A 2011 update from ACIP recommends an additional dose of meningococcal vaccine at age 16, to extend protection into the college years.

The quadrivalent meningococcal conjugate vaccine protects against the different illnesses caused by certain strains of Neisseria meningitidis bacteria. These illnesses together are referred to as meningococcal disease. Meningococcal bacteria can cause bloodstream infections, infection of the lining of the brain (meningitis), pneumonia, ear infections, and other infections.

Meningococcal meningitis symptoms include fever, headache, confusion and stiff neck, which may also be accompanied by nausea, vomiting, and sensitivity to light. Meningococcal bloodstream infection symptoms include sudden fever onset and rash.

Invasive meningococcal disease can be fatal; survivors may have permanent injury, including brain damage, hearing loss, or loss of limbs.

Another meningococcal vaccine that provides protection from certain serogroup B strains is available to adolescents. The ACIP declined in 2015 to make a recommendation that all adolescents routinely receive this vaccine; rather, the ACIP supported individual decision making about this vaccine. During ongoing outbreaks of disease caused by serogroup B meningococcal bacteria, the ACIP recommends routine use of this vaccine in individuals at risk of exposure.

Human Papillomavirus Vaccine

The recommended age for human papillomavirus (HPV) vaccination of females and males is 11-12 years. The vaccination is a three-dose series of intramuscular shots.

Human papillomaviruses belong to a large family of viruses, and the vaccine protects against some of the virus types that are sexually transmitted. Most people who contract HPV have no symptoms, and they quickly clear the virus from their bodies. However, in some people the viruses establish persistent infection, causing changes to infected cells that can lead to cancer. Indeed, HPVs are the main cause of cervical cancer, and some are associated with anal, penile, mouth, and throat cancers. The HPV vaccine protects against the most common types of cancer-causing human papillomaviruses. One of the licensed HPV vaccines also protects again certain HPVs that cause genital warts.

HPV is very common: one recent study showed that nearly 27% of girls and women aged 14-59 tested positive for one or more strains of HPV. Rates for boys and men are likely to be similar. Mathematical models have shown that more than 80% of women will have been infected with genital HPV by the time they reach age 50. According to the American Cancer Society, each year about 11,000 U.S. women are diagnosed with cervical cancer, and about 4,000 die from it.

Influenza Vaccine

Seasonal influenza vaccination is recommended yearly for all adolescents and teenagers; in fact, it is recommended for everyone over the age of 6 months. The vaccine protects against respiratory illness caused by influenza viruses. Because new strains of influenza appear frequently, the seasonal flu vaccine usually changes each year. Each season’s vaccine is designed to protect against three or four strains of influenza. Influenza vaccine is available as an injected or inhaled vaccine.

Symptoms of influenza (also commonly called flu) tend to emerge suddenly and include fever, chills, coughing, sore throat, achiness, headaches, and fatigue. Vomiting and diarrhea may also occur, but these symptoms are more common for children than for adults. Influenza symptoms typically last about week. Complications from influenza can lead to ear and sinus infections, pneumonia, and, uncommonly, death.

Other Vaccines

Teenagers with special health needs may be more vulnerable to certain illnesses and require vaccines to protect them. For example, teenagers who have dysfunctions of the immune system may be recommended to receive the pneumococcal vaccine, as they are at risk of serious disease from Streptococcus pneumoniae. Some vaccines are required or recommended before travel to certain countries. Additionally, teenagers who have not received vaccines recommended for early childhood may require “catch-up” vaccination so that they are fully protected.

School Requirements

The beginning of middle school is a trigger in many states for certain vaccine requirements for school attendance. The most commonly required adolescent immunizations are a booster dose of the tetanus, diphtheria, acellular pertussis (Tdap) vaccine and the meningococcal vaccine. Virginia and the District of Columbia require the human papillomavirus (HPV) vaccine for middle school entrance for girls. Some states require that adolescents be immunized with two doses of the measles, mumps, and rubella vaccine and one or two doses of the chickenpox (varicella) vaccine. Normally, the second doses of MMR and varicella are given at age 4-6. If a child did not receive the second dose by the beginning of middle school, the booster would be required.

Adolescents who do not have and will not receive the vaccines required for school entry may need to have their parents file medical, religious, or philosophical belief exemptions with the state government or school district, or face the possibility of being denied entrance to school.

School-based Immunization Programs

In some areas, school districts offer immunizations programs in the schools. School nurses or nurses provided by an outside organization may administer the vaccines. One challenge of school-based immunization is coordinating medical records with the student’s primary care provider.

School vaccine programs commonly include the seasonal influenza vaccine, which is recommended for all adolescents and must be given every year. HPV vaccination has been provided to girls in schools several places, such as New Zealand, Australia, and Great Britain.

Looking to the Adult Years

As they near adulthood, teenagers can prepare to manage their own healthcare by discussing immunization with their doctors and parents. They can find out whether they are up-to-date with their shots and which vaccines are recommended for them. If they plan to go to college, join the military, or switch to a new healthcare provider, teenagers should make sure that they have a copy of their immunization history to include with their medical records.

Resources for Teenagers

Teens Health: Immunizations

CDC: Preteens and Teens Need Vaccines Too

Resources for Parents

CDC: For Parents: Preteen and Teen Vaccines

Vaccine Education Center: A Look at Each Vaccine: Human Papillomavirus Vaccine

 


Sources

American Cancer Society. What are the key statistics about cervical cancer? Accessed 04/05/2017.

Centers for Disease Control and Prevention. Flu Vaccination Coverage, United States, 2014-15 Influenza Season. Accessed 04/05/2017.

Centers for Disease Control and Prevention. National, Regional, State, and Selected Local Area Vaccination Coverage Among Adolescents Aged 13 Through 17 Years — United States, 2014. MMWR 64(29);784-92. Accessed 04/05/2017.

Centers for Disease Control and Prevention. School vaccination requirements, exemptions, and web links: HPV. Accessed 04/05/2017.

Centers for Disease Control and Prevention. Use Serogroup B Meningococcal Vaccines in Adolescents and Young Adults: Recommendations of the Advisory Committee on Immunization Practices, 2015. MMWR  64(41);1171-6. Accessed 04/05/2017.

Immunization Action Coalition. State mandates on immunization and vaccine-preventable diseases. Accessed 04/05/2017.

National Conference of State Legislatures. HPV Vaccine: State Legislation and Statutes. Accessed 04/05/2017.

Last update 05 April 2017

Vaccines for Adults

Vaccines for Adults

Vaccines are most often discussed in the context of childhood, where they’re given according to a recommended schedule to prevent common (and not-so-common) childhood illnesses. Frequent and routine “well child” visits to the doctor help ensure that children are kept up-to-date on their vaccines.

With fewer doctor visits as we age, however, the percentage of the population that is up-to-date on recommended vaccines wanes. Data from the U.S. Centers for Disease Control and Prevention show that only about half of all teenagers have received the recommended meningococcal vaccine, which protects against bacterial infections that may lead to amputation of infected limbs and death. Similarly, only about half of adolescents received the recommended influenza vaccine during the 2010-2011 flu season. By adulthood, many of us have forgotten that vaccines are available – and important – for everyone, not just kids.

Apart from protecting themselves, adults should consider the benefits of vaccination to the family and community. In most cases, a person who is vaccinated against a disease cannot spread that disease to other people. High rates of vaccination help protect those around us who cannot be immunized for health reasons (such as illness, age, or allergy). This principle is known as herd immunity, or community immunity.

Following are vaccines typically recommended for adults. Note that younger adults may have received vaccines that were more recently developed, such as those against chickenpox or hepatitis A, as children. If so, they may not need to receive the vaccines again.

If you think you may need to receive one or more of these vaccines, consult your doctor.

Pneumococcal Vaccine

Pneumococcal disease includes a variety of illnesses caused by the bacterium Streptococcus pneumoniae. Different types of pneumococcal disease include pneumococcal bacteremia, meningitis, and pneumonia.

The pneumococcal vaccine is recommended for adults based on a variety of risk factors. It is recommended for the following groups:

  • Anyone who is 65 or older
  • Anyone between 19 and 65 years of age with asthma, or who is a smoker
  • Anyone between the ages of 2 and 65 with one of the following long-term health problems:heart disease, lung disease, sickle cell disease, diabetes, alcoholism, cirrhosis, leaks of cerebrospinal fluid, or cochlear implant
  • Anyone between the ages of 2 and 65 with a condition that lowers resistance to infection, including lymphoma, leukemia, HIV or AIDS, kidney failure, a damaged or missing spleen, or organ transplant
  • Anyone between the ages of 2 and 65 receiving a treatment that lowers resistance to infection, including radiation therapy, some cancer drugs, or long-term steroids
  • Anyone living in a nursing home or long-term care facility

Human papillomavirus (HPV) Vaccine

HPV vaccines protect against multiple strains of HPV that cause cervical, vaginal, and vulvar cancer. One of the two HPV vaccines also provides protection against genital warts.

HPV vaccination is recommended for children as part of the routine childhood immunization schedule, but is also recommended for adults who were not vaccinated as children.

  • Women who are 26 years old or younger can receive either version of the HPV vaccine for protection against cervical, vaginal, and vulvar cancer. The vaccine may also provide protection against oral and anal cancer, and the quadrivalent version of the vaccine protects against genital warts.
  • Men who are 26 years old or younger can receive the quadrivalent vaccine, which offers protection against genital warts and may protect against oral, anal, and penile cancer caused by HPV.

Influenza Vaccine

Seasonal influenza vaccination is recommended yearly for all adults; in fact, it is recommended for everyone over the age of 6 months. The vaccine protects against respiratory illness caused by influenza viruses. Because new strains of influenza appear frequently, the seasonal flu vaccine usually changes each year. Each season’s vaccine is designed to protect against three strains of influenza. Influenza vaccine is available as an injected or inhaled vaccine, but for adults 50 years of age and older, only the injectable vaccine is recommended.

Tetanus/Diphtheria and Tetanus/Diphtheria/Pertussis Booster Vaccines

A combination vaccine against tetanus, diphtheria, and pertussis (whooping cough) is given in childhood in a series of shots called DTaP. After that, everyone needs a booster shot for tetanus and diphtheria every 10 years, given in the form of a vaccine called Td. One of those boosters, however, should be replaced with a shot of the Tdap vaccine (which provides protection against tetanus, diphtheria, and pertussis). A Tdap booster is particularly recommended for health care workers and anyone who has contact with an infant. (This is because infants are too young to receive their own vaccination against whooping cough, which can be fatal in young children. Therefore, it is important that anyone in contact with the child be protected against whooping cough so as not to expose the child to the disease.) Pregnant women are recommended to take the Tdap vaccine during the last trimester of each pregnancy in order to protect the baby via maternal antibody until age 2 months. At two months of age, the baby can receive DTaP.

Separate from routine boosters given every 10 years, Td is also given to individuals who have suffered injuries or wounds that may have exposed them to tetanus bacteria. Tdap can also be used in this instance, to provide protection against pertussis.

Hepatitis A Vaccine

Hepatitis A vaccines were added to the routine childhood immunization schedule in 2006, but are also recommended for adults who are at an increased risk for hepatitis A. This includes the following groups:

  • Anyone traveling to developing countries
  • Men who have sex with men
  • Anyone who uses illegal drugs
  • Anyone who works with non-human primates infected with hepatitis A, or who works with hepatitis A in a research setting
  • Anyone with chronic liver disease
  • Anyone with clotting factor disorders

Separately, hepatitis A vaccination may be considered for food handlers because of their potential to transmit the virus to others.

Hepatitis B Vaccine

Hepatitis B vaccines were added to the routine childhood immunization schedule in 1991, but are also recommended for adults who are at an increased risk for hepatitis B. This includes the following groups:

  • Anyone living with or having sex with a hepatitis B-infected person
  • Anyone having sex with multiple partners
  • Anyone seeking treatment for sexually transmitted diseases, HIV testing (or treatment), or drug treatment
  • Men who have sex with men
  • Anyone who uses illegal drugs
  • Anyone with a job that involves direct contact with human blood
  • Anyone who works in facilities for the developmentally disabled
  • Anyone who receives hemodialysis or has end-stage kidney disease
  • Anyone who has HIV
  • Anyone who receives dialysis
  • Anyone with chronic liver disease
  • Anyone who is a prisoner in a correctional facility
  • Anyone who is traveling to a country where the virus is common 

Measles, Mumps, and Rubella (MMR) Vaccine

Any adult born in the United States before 1957 is considered immune to both measles and mumps because the diseases were so widespread in the pre-vaccine era.

Individuals who were born after 1957 may need to receive booster shots or be revaccinated with MMR if they are members of one of the following groups:

  • Anyone who is a college student
  • Anyone who is a health care worker
  • Anyone traveling internationally (particularly to countries with high rates of measles, mumps or rubella – a travel clinic can provide additional information)
  • Anyone who received the killed measles vaccine, or a measles vaccine of unknown type, from 1963 to 1967. (The immunity provided by the killed vaccine was not adequate, and individuals immunized with this vaccine may not be protected against measles. Your doctor can provide more information.)
  • Women of childbearing age who want to become pregnant and have no evidence of immunity against rubella

Chickenpox (varicella) Vaccine

The chickenpox vaccine was added to the recommended childhood immunization schedule in 1996, but is also recommended for adults with no evidence of chickenpox immunity.

Anyone born in the United States before 1980 is considered immune to chickenpox. (Note: health care workers and pregnant women born before 1980 are not considered immune for the purposes of determining whether the vaccine should be administered. Health care workers should receive the vaccine; pregnant women should receive the first dose of the vaccine after the completion of their pregnancies.)

Anyone born in 1980 or later should receive the varicella vaccine unless they can provide documentation of having received two doses of the vaccine at least one month apart, or of having had a case of chickenpox or herpes zoster diagnosed by a doctor and/or confirmed by a laboratory.

Shingles (zoster) Vaccine

The shingles vaccine is licensed by the Food and Drug Administration for individuals who are 50 years of age or older. The vaccine is recommended for anyone who is 60 years of age or older, even if they have reported a previous case of shingles.

Meningococcal Vaccine

Meningococcal disease includes a variety of illnesses caused by the bacterium, Neisseria meningitidisDifferent types of meningococcal disease include meningococcal meningitis and meningococcemia (blood infection). 

The meningococcal vaccine is recommended for adults based on a variety of risk factors. It is recommended for the following groups:

  • Anyone who is a member of the military
  • Anyone with a damaged or removed spleen
  •  Anyone doing research that exposes him/her to Neisseria meningitidis 
  •  Anyone traveling to a country where meningococcal disease is common
  • Anyone with terminal complement deficiency
  • Anyone starting college who has not received a dose of the vaccine during the past five years

Travel Vaccines

In addition to the vaccines listed above, some of which are recommended if you are traveling to an area with a large number of cases of the diseases they prevent, other vaccines may be recommended if you are traveling internationally.

In addition, some vaccines may be required before you are allowed to enter a particular country or region. For example, if you are traveling to certain countries in tropical South America or sub-Saharan Africa, international health regulations require that you be vaccinated against yellow fever. (These requirements made national news in 2011, when the World Cup was held in South Africa. South Africa requires proof of yellow fever vaccination before issuing travel visas, and fans in Uganda, where there was a shortage of the vaccine, scrambled to be immunized in time to travel.)

Vaccines that may be recommended before traveling internationally, particularly to developing countries, include those against typhoidrabies, and Japanese encephalitis. More information can be found on the Centers for Disease Control and Prevention’s Travelers’ Health website, where you can search by destination or locate a clinic that specializes in travel health. In addition to vaccines, travel medicine centers can advise on important issues such as the prevention of malaria and the prevention and potential treatment of travel related illnesses such as diarrhea.

Sources and More Information

Centers for Disease Control and Prevention. Prevention of Hepatitis A Through Active or Passive Immunization: Recommendations of the Advisory Committee on Immunization Practices. December 27, 1996. Accessed 04/05/2017.

Centers for Disease Control and Prevention. Vaccines: Hepatitis A In-Short. CDC website. Accessed 04/05/2017.

Centers for Disease Control and Prevention. Vaccines: Hepatitis B In-Short. CDC website. Accessed 04/05/2017.

Centers for Disease Control and Prevention. Vaccines: Meningococcal: What Everyone Should Know. CDC website. Accessed 04/05/2017.

Centers for Disease Control and Prevention. Vaccines: Pneumococcal Vaccination: What Everyone Should Know. CDC website. Accessed 04/05/2017.

Immunization Action Coalition. Vaccinations for Adults. IAC website. 2012. (152 KB). Accessed 04/05/2017.

 

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Last update 05 April 2017

Different Types of Vaccines

Different Types of Vaccines

The first human vaccines against viruses were based using weaker or attenuated viruses to generate immunity. The smallpox vaccine used cowpox, a poxvirus that was similar enough to smallpox to protect against it but usually didn’t cause serious illness. Rabies was the first virus attenuated in a lab to create a vaccine for humans.

Vaccines are made using several different processes. They may contain live viruses that have been attenuated (weakened or altered so as not to cause illness); inactivated or killed organisms or viruses; inactivated toxins (for bacterial diseases where toxins generated by the bacteria, and not the bacteria themselves, cause illness); or merely segments of the pathogen (this includes both subunit and conjugate vaccines).

Vaccine type Vaccines of this type on U.S. Recommended Childhood (ages 0-6) Immunization Schedule
Live, attenuated Measles, mumps, rubella (MMR combined vaccine)
Varicella (chickenpox)
Influenza (nasal spray)
Rotavirus
Inactivated/Killed Polio (IPV)
Hepatitis A
Toxoid (inactivated toxin) Diphtheria, tetanus (part of DTaP combined immunization)
Subunit/conjugate Hepatitis B
Influenza (injection)
Haemophilus influenza type b (Hib)
Pertussis (part of DTaP combined immunization)
Pneumococcal
Meningococcal
Vaccine type Other available vaccines
Live, attenuated Zoster (shingles)

Yellow fever

Inactivated/Killed Rabies
Subunit/conjugate Human papillomavirus (HPV)

Live, attenuated vaccines currently recommended as part of the U.S. Childhood Immunization Schedule include those against measles, mumps, and rubella (via the combined MMR vaccine), varicella (chickenpox), and influenza (in the nasal spray version of the seasonal flu vaccine). In addition to live, attenuated vaccines, the immunization schedule includes vaccines of every other major type—see the table above for a breakdown of the vaccine types on the recommended childhood schedule.

The different vaccine types each require different development techniques. Each section below  addresses one of the vaccine types.

Live, Attenuated Vaccines

Attenuated vaccines can be made in several different ways. Some of the most common methods involve passing the disease-causing virus through a series of cell cultures or animal embryos (typically chick embryos). Using chick embryos as an example, the virus is grown in different embryos in a series. With each passage, the virus becomes better at replicating in chick cells, but loses its ability to replicate in human cells. A virus targeted for use in a vaccine may be grown through—“passaged” through—upwards of 200 different embryos or cell cultures. Eventually, the attenuated virus will be unable to replicate well (or at all) in human cells, and can be used in a vaccine. All of the methods that involve passing a virus through a non-human host produce a version of the virus that can still be recognized by the human immune system, but cannot replicate well in a human host.

When the resulting vaccine virus is given to a human, it will be unable to replicate enough to cause illness, but will still provoke an immune response that can protect against future infection.

One concern that must be considered is the potential for the vaccine virus to revert to a form capable of causing disease. Mutations that can occur when the vaccine virus replicates in the body may result in more a virulent strain. This is very unlikely, as the vaccine virus’s ability to replicate at all is limited; however, it is taken into consideration when developing an attenuated vaccine. It is worth noting that mutations are somewhat common with the oral polio vaccine (OPV), a live vaccine that is ingested instead of injected. The vaccine virus can mutate into a virulent form and result in rare cases of paralytic polio. For this reason, OPV is no longer used in the United States, and has been replaced on the Recommended Childhood Immunization Schedule by the inactivated polio vaccine (IPV).

Protection from a live, attenuated vaccine typically outlasts that provided by a killed or inactivated vaccine.

Killed or Inactivated Vaccines

One alternative to attenuated vaccines is a killed or inactivated vaccine. Vaccines of this type are created by inactivating a pathogen, typically using heat or chemicals such as formaldehyde or formalin. This destroys the pathogen’s ability to replicate, but keeps it “intact” so that the immune system can still recognize it. (“Inactivated” is generally used rather than “killed” to refer to viral vaccines of this type, as viruses are generally not considered to be alive.)

Because killed or inactivated pathogens can’t replicate at all, they can’t revert to a more virulent form capable of causing disease (as discussed above with live, attenuated vaccines). However, they tend to provide a shorter length of protection than live vaccines, and are more likely to require boosters to create long-term immunity. Killed or inactivated vaccines on the U.S. Recommended Childhood Immunization Schedule include the inactivated polio vaccine and the seasonal influenza vaccine (in shot form).

Toxoids

Some bacterial diseases are not directly caused by a bacterium itself, but by a toxin produced by the bacterium. One example is tetanus: its symptoms are not caused by the Clostridium tetani bacterium, but by a neurotoxin it produces (tetanospasmin). Immunizations for this type of pathogen can be made by inactivating the toxin that causes disease symptoms. As with organisms or viruses used in killed or inactivated vaccines, this can be done via treatment with a chemical such as formalin, or by using heat or other methods.

Immunizations created using inactivated toxins are called toxoids. Toxoids can actually be considered killed or inactivated vaccines, but are sometimes given their own category to highlight the fact that they contain an inactivated toxin, and not an inactivated form of bacteria.

Toxoid immunizations on the U.S. Recommended Childhood Immunization schedule include the tetanus and diphtheria immunizations, which are available in a combined form.

Subunit and Conjugate Vaccines

Both subunit and conjugate vaccines contain only pieces of the pathogens they protect against.

Subunit vaccines use only part of a target pathogen to provoke a response from the immune system. This may be done by isolating a specific protein from a pathogen and presenting it as an antigen on its own. The acellular pertussis vaccine and influenza vaccine (in shot form) are examples of subunit vaccines.

Another type of subunit vaccine can be created via genetic engineering. A gene coding for a vaccine protein is inserted into another virus, or into producer cells in culture. When the carrier virus reproduces, or when the producer cell metabolizes, the vaccine protein is also created. The end result of this approach is a recombinant vaccine: the immune system will recognize the expressed protein and provide future protection against the target virus. The Hepatitis B vaccine currently used in the United States is a recombinant vaccine.

Another vaccine made using genetic engineering is the human papillomavirus (HPV) vaccine. Two types of HPV vaccine are available—one provides protection against two strains of HPV, the other four—but both are made in the same way: for each strain, a single viral protein is isolated. When these proteins are expressed, virus-like particles (VLPs) are created. These VLPs contain no genetic material from the viruses and can’t cause illness, but prompt an immune response that provides future protection against HPV.

Conjugate vaccines are somewhat similar to recombinant vaccines: they’re made using a combination of two different components. Conjugate vaccines, however, are made using pieces from the coats of bacteria. These coats are chemically linked to a carrier protein, and the combination is used as a vaccine. Conjugate vaccines are used to create a more powerful, combined immune response: typically the “piece” of bacteria being presented would not generate a strong immune response on its own, while the carrier protein would. The piece of bacteria can’t cause illness, but combined with a carrier protein, it can generate immunity against future infection. The vaccines currently in use for children against pneumococcal bacterial infections are made using this technique.

More Information

Researchers continue to develop new vaccine types and improve current approaches. For more information about experimental vaccines and delivery techniques, see our article The Future of Immunization.


Sources

Plotkin, S.A., Mortimer, E. Vaccines. New York: Harper Perennial; 1988.

Plotkin, S.A., Orenstein, W.A., Offit, P.A., eds. Vaccines. 6th. ed. Philadelphia: Elsevier; 2013.

 

Last update 19 April 2017

The Human Immune System and Infectious Disease

The Human Immune System and Infectious Disease

All living things are subject to attack from disease-causing agents. Even bacteria, so small that more than a million could fit on the head of a pin, have systems to defend against infection by viruses. This kind of protection gets more sophisticated as organisms become more complex.

Multicellular animals have dedicated cells or tissues to deal with the threat of infection. Some of these responses happen immediately so that an infecting agent can be quickly contained. Other responses are slower but are more tailored to the infecting agent. Collectively, these protections are known as the immune system. The human immune system is essential for our survival in a world full of potentially dangerous microbes, and serious impairment of even one arm of this system can predispose to severe, even life-threatening, infections.

Non-Specific (Innate) Immunity

The human immune system has two levels of immunity: specific and non-specific immunity. Through non-specific immunity, also called innate immunity, the human body protects itself against foreign material that is perceived to be harmful. Microbes as small as viruses and bacteria can be attacked, as can larger organisms such as worms. Collectively, these organisms are called pathogens when they cause disease in the host.

All animals have innate immune defenses against common pathogens. These first lines of defense include outer barriers like the skin and mucous membranes. When pathogens breach the outer barriers, for example through a cut in the skin or when inhaled into the lungs, they can cause serious harm.

Some white blood cells (phagocytes) fight pathogens that make it past outer defenses. A phagocyte surrounds a pathogen, takes it in, and neutralizes it.

Specific Immunity

While healthy phagocytes are critical to good health, they are unable to address certain infectious threats. Specific immunity is a complement to the function of phagocytes and other elements of the innate immune system.

In contrast to innate immunity, specific immunity allows for a targeted response against a specific pathogen. Only vertebrates have specific immune responses.

Two types of white blood cells called lymphocytes are vital to the specific immune response. Lymphocytes are produced in the bone marrow, and mature into one of several subtypes. The two most common are T cells and B cells.

An antigen is a foreign material that triggers a response from T and B cells. The human body has B and T cells specific to millions of different antigens. We usually think of antigens as part of microbes, but antigens can be present in other settings. For example, if a person received a blood transfusion that did not match his blood type, it could trigger reactions from T and B cells.

A useful way to think of T cells and B cells is as follows: B cells have one property that is essential. They can mature and differentiate into plasma cells that produce a protein called an antibody. This protein is specifically targeted to a particular antigen. However, B cells alone are not very good at making antibody and rely on T cells to provide a signal that they should begin the process of maturation. When a properly informed B cell recognizes the antigen it is coded to respond to, it divides and produces many plasma cells. The plasma cells then secrete large numbers of antibodies, which fight specific antigens circulating in the blood.

T cells are activated when a particular phagocyte known as an antigen-presenting cell (APC) displays the antigen to which the T cell is specific. This blended cell (mostly human but displaying an antigen to the T cell) is a trigger for the various elements of the specific immune response.

A subtype of T cell known as a T helper cell performs a number of roles. T helper cells release chemicals to

  • Help activate B cells to divide into plasma cells
  • Call in phagocytes to destroy microbes
  • Activate killer T cells

Once activated, killer T cells recognize infected body cells and destroy them.

Regulatory T cells (also called suppressor T cells) help to control the immune response. They recognize when a threat has been contained and then send out signals to stop the attack.

Organs and Tissues

The cells that make up the specific immune response circulate in the blood, but they are also found in a variety of organs. Within the organ, immune tissues allow for maturation of immune cells, trap pathogens and provide a place where immune cells can interact with one another and mount a specific response. Organs and tissues involved in the immune system include the thymus, bone marrow, lymph nodes, spleen, appendix, tonsils, and Peyer’s patches (in the small intestine).

Infection and Disease

Infection occurs when a pathogen invades body cells and reproduces. Infection will usually lead to an immune response. If the response is quick and effective, the infection will be eliminated or contained so quickly that the disease will not occur.

Sometimes infection leads to disease. (Here we will focus on infectious disease, and define it as a state of infection that is marked by symptoms or evidence of illness.) Disease can occur when immunity is low or impaired, when virulence of the pathogen (its ability to damage host cells) is high, and when the number of pathogens in the body is great.

Depending on the infectious disease, symptoms can vary greatly. Fever is a common response to infection: a higher body temperature can heighten the immune response and provide a hostile environment for pathogens. Inflammation, or swelling caused by an increase in fluid in the infected area, is a sign that white blood cells are on the attack and releasing substances involved in the immune response.

Vaccination works to stimulate a specific immune response that will create memory B and T cells specific to a certain pathogen. These memory cells persist in the body and can lead to a quick and effective response should the body encounter the pathogen again.

For more on vaccination, see the activity How Vaccines Work.


Sources

Hunt, R. Virology: Rhinoviruses. Microbiology and Immunology Online. University of South Carolina. Accessed 03/15/2017.

The Merck Manual: Home Edition. Infections. Accessed 03/15/2017.

Delves, P.J. The Merck Manual: Home Edition. Overview of the Immune System. Accessed 03/15/2017.

Last update 15 March 2017

Shingles (Herpes Zoster)

Shingles (Herpes Zoster)

Cause and Symptoms

Shingles, or herpes zoster, is caused by the Varicella zoster virus. This is the same virus that causes chickenpox. Shingles can develop only after initial infection with chickenpox, or, more uncommonly, after vaccination for chickenpox. After a person recovers from chickenpox (or after vaccination), the virus remains in the body, located around nerve cell clusters in the head and along the spine. Many years after the initial infection (or vaccination), the virus can be reactivated and cause symptoms.

The first symptoms of shingles are often pain, burning, or itching along a band of skin on a single side of the body, usually on the head, neck, or trunk. These bands of skin correspond to nerve cells where the virus has been activated. In a few days, a rash and blisters erupt on the skin in a band that follows the nerve’s path. Fever, headache, and achiness may also occur. Typically, blisters crust over and scab within 2-3 weeks.

Facts about Shingles

  • Shingles can occur at any age, but it is most common in people over age 60 and in people with weakened immune systems.
  • Shingles can recur, although most people who experience shingles have it just once in their lifetime.
  • About 1 million cases of shingles occur in the United States each year.

Transmission

A person with shingles cannot give shingles to someone else. However, a person with shingles can transmit Varicella zoster to a person who is not immune to the virus. In that case, the person would develop chickenpox, not shingles.

Transmission occurs via the fluid from the shingles blisters. A person is infectious from the time the blisters appear to the time the blisters crust over and no longer contain fluid. Accordingly, people with shingles blisters are advised to avoid bringing blistered areas in contact with others.

Treatment and Care

There is no cure for shingles. Certain antiviral medications can reduce the severity and duration of shingles when they are taken soon after symptom onset.

Care for shingles usually includes use of pain medications and topical treatments for blistered areas.

Complications

The most common complication from shingles is a condition called post-herpetic neuralgia. This occurs when the infected nerve is damaged and causes pain even after the shingles blisters disappear. Pain may be mild or severe, and it may last months or even years.

Other complications that may result from shingles are skin infections, eye infections, and neurological complications.

Available Vaccines and Vaccination Campaigns

Since 2008, the U.S. Advisory Committee on Immunization Practices has recommended that most Americans age 60 and older get the shingles vaccine. Adults 50-59 may also get the vaccine.

The vaccine reduces risk of shingles about 50%, and it reduces the risk of post-herpetic neuralgia by nearly 70%.

The shingles vaccine is a live, attenuated vaccine and is not recommended for people with weakened immune systems. It was licensed in 2006. The generic name of the vaccine is Zoster Vaccine, Live (tradename Zostavax).

Most Medicare drug plans (Part D) cover the cost of the vaccine and its administration, minus any copayments. Most private insurance plans provide coverage for the vaccination for people 60 and older. However, because the vaccination is not on the recommended adult immunization schedule for adults age 50-59, most insurance plans do not provide a benefit for shingles vaccination for this group of people.


Sources

Centers for Disease Control and Prevention. Prevention of herpes zoster. Recommendation of the Advisory Committee on Immunization Practices (ACIP). MMWR. 2008. 57(05);1-30. Accessed 04/12/2017.

Centers for Disease Control and Prevention. Shingles (herpes zoster) clinical overview. Accessed 04/12/2017.

Centers for Disease Control and Prevention. Varicella. Epidemiology and Prevention of Vaccine-Preventable Diseases, 13thed. 2015. Accessed 04/12/2017.

Merck. Zostavax package insert. (159 KB). Accessed 04/12/2017.

Last update 12 April 2017

Chickenpox (Varicella)

Chickenpox (Varicella)

Cause and Symptoms

Chickenpox is an illness caused by the Varicella zoster virus. It was once an almost universal childhood experience. Now it is much less common in the United States owing to widespread vaccination.

In children, the first symptom of chickenpox is usually an itchy rash that appears on the head and spreads down to the trunk and other body parts. The rash becomes raised, and blisters form. Blisters may also form on mucous membranes, such as inside the mouth, nose, throat, and vagina. The blisters crust over and disappear within about 10-14 days. In adults the first symptoms of chickenpox may be fever and tiredness a few days before the rash appears. Children may also have fever and tiredness along with the rash.

People who have had chickenpox are at risk later in life for shingles, which occurs when the Varicella zoster virus is reactivated. In uncommon cases, vaccination for chickenpox can also cause shingles to develop eventually. Read more in the shingles article.

Transmission

Chickenpox is easily transmissible from person to person. About 90% of non-immune household contacts of someone infected with chickenpox will contract the disease.

Transmission of chickenpox occurs via infected respiratory tract secretions, respiratory droplets, and fluid from the blisters. A person is infectious from one to two days before the rash appears to the time the blisters crust over and no longer contain fluid.

Treatment and Care

There is no cure for chickenpox. Care for chickenpox usually includes use of pain medications and topical treatments for the itchy rash, blisters, and scabs.

In serious cases of varicella, antiviral drugs can alter the course of the illness. These are typically given early to people at highest risk of complications, including sick children and pregnant women.

Complications

Chickenpox is usually a mild disease in children, and they generally do not experience complications. In some cases, however, secondary bacterial infections related to lesions can occur. Other possible complications include pneumonia and neurological complications. Complications are more likely for children under age 1, anyone over age 15, and people who have weakened immune systems. Chickenpox infection in pregnancy can be risky to the mother, to the pregnancy, and to the newborn.

Available Vaccines and Vaccination Campaigns

The U.S. Advisory Committee on Immunization Practices recommends two doses of the chickenpox vaccine for most children. The first dose is given around age 1 and the second around ages 4-6. A single dose of the vaccine reduces risk of chickenpox between 70-90%, and two doses reduce the risk even more.

The chickenpox vaccine is a live, attenuated vaccine and is not recommended for people with weakened immune systems. It is available as a single vaccine, and it is also available as part of the MMRV vaccine (measles, mumps, rubella, and varicella vaccine).

The chickenpox vaccine was added to the childhood immunization schedule in 1995. The booster dose was added in 2006.

When chickenpox occurs in vaccinated individuals, these cases are known as breakthrough cases. Breakthrough cases are usually very mild compared with the disease in unvaccinated individuals.

Not all states report chickenpox cases to the CDC, and so it is difficult to know how many cases occur yearly in the United States. However, before introduction of the vaccine it was generally thought that the equivalent of an entire birth cohort each year, roughly 4 million individuals, was infected. Studies of the effects of two-dose vaccination in select areas have found that incidence has fallen about 90% from the pre-vaccine era.


Sources

Bialek, S.R., Perella, D., Zhang, J., Mascola, L., Viner, K., Jackson, C., Lopez, A.S., Barbara, W., Civen, R. Impact of a routine two-dose varicella vaccination program on varicella epidemiology. Pediatrics. 10/07/2013; doi:10.1542/peds.2013-086. Accessed 04/12/2017.

Centers for Disease Control and Prevention. Varicella. In: Epidemiology and Prevention of Vaccine-Preventable Diseases, 13thed. 2015. Accessed 04/12/2017.

Centers for Disease Control and Prevention. Prevention of varicella. Recommendations of the Advisory Committee on Immunization Practices. MMWR. 2007. 56(RR04);1-40. Accessed 04/12/2017.

Last update 04/12/2017

Cancer Vaccines and Immunotherapy

Cancer Vaccines and Immunotherapy

Background for this article can be found in The Human Immune System and Infectious Diseases and Vaccine Development, Testing, and Regulation

Cancer vaccines are not just a dream for the future: several FDA-approved vaccines are cancer prevention vaccines. The hepatitis B vaccine and the human papillomavirus (HPV) vaccines prevent infection with cancer-causing viruses.[1] By preventing the viruses from infecting body cells, these vaccines block the process that might eventually result in runaway cancer cell growth and damage to the body.

Viruses, however, do not cause most cancers.[2] The challenge for researchers is to use the model of the immune response to viral infection of cells to develop vaccines for cancers not caused by viruses.

This idea is not so far fetched. Just as the immune system constantly works to protect the body from harmful viruses and bacteria, it also plays a vital role in protecting the body from cancer. Many cancerous cells express markers, called antigens, that act as targets for the immune system. In many cases, immune cells recognize the cancerous cells and destroy them. However, some cancerous cells are able to hide from the immune system or suppress it, or large numbers of cancerous cells simply overwhelm the immune system’s ability to clear the cells.[3] The cancer cells are then able to divide and spread unchecked, damaging tissues and organs as they do.

Today’s researchers are devising vaccines they hope will trigger the immune system to attack cancer cells reliably and effectively. They are also exploring other ways to boost the immune system’s response to cancerous cells.

Therapeutic Vaccines

The HPV and hepatitis B vaccines are preventive vaccines. That is, they work by preventing an infection that might lead to cancer. A therapeutic cancer vaccine, on the other hand, would be used to treat cancer after it has already appeared. There are two main types of such therapeutic vaccines: autologous vaccines and allogenic vaccines.

Autologous cancer vaccines Autologous means “derived from oneself” – so an autologous vaccine is a personalized vaccine made from an individual’s own cells—either cancer cells or immune system cells.

To make an autologous cancer cell cancer vaccine, cells from a person’s tumor are removed from the body and treated in a way that makes them a target for the immune system. They are then injected into the body, where immune cells recognize them, disable them, and then do the same to other cancer cells in the body. Ideally, memory immune cells would persist in the body and be able to respond if cancer cells returned. The goal may be to treat the cancer present in the body or to prevent tumors from recurring after more conventional cancer treatments like surgery, radiation, or chemotherapy, have eliminated most or all of the cancer.[4]

Several Phase 2 and Phase 3 trials of such autologous cancer cell vaccines are in process or have been completed, though none has been licensed.[5]

Another approach to autologous cancer vaccines is to use an individual’s own immune cells to make the vaccine. The US FDA has licensed one autologous vaccine made from immune cells. Sipuleucel-t (Provenge®) is an autologous immune cell prostate cancer vaccine. It has been shown in clinical trials to extend life for men with treatment-resistant metastatic prostate cancer.[6],[7]

Sipuleucel-t is produced and works in the following manner:

  1. Patient goes to lab to get blood drawn.
  2. Lab isolates a certain type of immune cell from patient’s blood.
  3. Lab technicians expose the immune cells to a prostate-cancer antigen fused with an immune-cell stimulator.
  4. Treated immune cells are infused back into the patient.
  5. Treated immune cells signal other immune cells to attack prostate cancer cells.

Several Phase 2 and Phase 3 trials of other autologous cancer cell vaccines are in process or have been completed. For example, researchers at the University of Pennsylvania have developed an experimental breast cancer vaccine. This vaccine uses immune cells from patients who have a certain type of early breast cancer: immune cells are extracted and exposed to a tumor antigen and immune-cell stimulators and then injected back into the body. The treated cells will then respond to cells expressing the target antigen. The strategy behind this particular vaccine is to use it in a very early stage of a certain type of breast cancer, before the body has become host to a very large population of cancer cells. The vaccine showed some promise in a Phase 1 trial: most of the vaccinated women had fewer cells expressing the tumor antigen after vaccine treatment than similar women who did not receive the vaccine[8]. Study on this vaccine continues.

Allogenic cancer vaccines “Allo-” means other. Allogenic cancer vaccines are made from non-self cancer cells grown in a lab.

Several allogenic cancer cell vaccines have been tested and are being tested, including vaccines to treat pancreatic cancer, melanoma (skin cancer), leukemia, non-small cell lung cancer, and prostate cancer. Allogenic cancer vaccines are appealing because they are less costly to develop and produce than autologous vaccines.[3] So far, none has been shown to be effective enough to be licensed.

Several allogenic immune cell vaccines have been tested in very early stages as well.[9],[10]

Protein or Peptide Cancer Vaccines

The autologous and allogenic vaccines discussed above are whole-cell vaccines: that is, they are made from entire cancer cells or immune system cells. But some cancer vaccines in development are made from parts of cancer cells. These parts are proteins from cells, or even smaller components called peptides, which are sections of proteins. These proteins and peptides can be delivered as a vaccine alone, coupled with carriers such as viruses, or in combination with immune-stimulating molecules.[2] As with most of the other therapeutic cancer vaccines, these protein or peptide vaccines for cancer are still in clinical trials.

DNA Vaccines

Another approach to therapeutic cancer vaccines uses DNA associated with tumor antigens to mount an immune response to an existing tumor. Generally, this involves vaccinating the cancer patient with a preparation containing DNA rings called plasmids. The plasmids, while not taken up into the patient’s own cellular DNA, prompt body cells to produce key tumor antigens. Those antigens then signal immune cells to start responding to similar antigens on existing cancer cells in the body.[11] Human trials of DNA vaccines to target many cancers, including breast cancer, HPV-related cancers, prostate cancer, and melanoma, are underway.[12]

Other Approaches

Vaccines that work in the ways described above are just one tool to harness the immune system to fight cancer. Other therapies, some used for cancer treatment for many years, work to enhance different parts of the immune system to mount specific responses to cancer-related antigens

BCG and bladder cancer BCG is a tuberculosis vaccine. It is made from live but weakened bacteria related to the ones that cause tuberculosis. BCG has been used for many decades as a treatment for early stage bladder cancer. BCG in solution is introduced into the bladder and left there for several hours. The patient voids the liquid after a time. Some of the bacteria remain in the bladder tissue and work as an immune system stimulant. They attract large numbers of infection-fighting cells to the bladder, where those cells also target the cancer cells.[2],[4]

Monoclonal Antibodies Antibodies are proteins that target antigens. They are produced in the body by immune system cells. Antibodies may mark an antigen for destruction, or they may prevent an antigen from attaching to a receptor on a body cell. Increasingly, technology is being used to generate monoclonal antibodies (MAbs)– “mono” meaning that they are a single type of antibody targeted at a particular antigen and “clonal” because they are produced from a single parent cell.

Some mABs work by attaching to antigens on cancer cells and marking them for destruction by other immune system cells. Other mABs signal immune system cells to attack cancer cells. Others interrupt signals that tell cancer cells to divide. One of the most widely used mABs, trastuzumab (Herceptin®), works this way: these mABs attach to growth factors on a certain type of breast cancer cell and lead the cells to stop dividing and die.[13]

mABs may be linked to radioactive or chemical agents—these are then called conjugated mABs. The conjugated mAB helps deliver the radioactive or chemical agent to a targeted cancer cell so that it can be destroyed.[4]

Cytokines             Cytokines are proteins secreted by immune system cells that play an important role in signaling to other immune system cells. For treatment of certain cancers, various cytokines are made in the lab. They are given to patients via injection into the skin or muscle, or into a vein. There are three types of cytokine therapies for cancer treatment:[4]

  • Interleukin boosts immune cell growth and division.
  • Interferon can help immune system cells neutralize cancer cells and may suppress cancer cell growth.
  • GMS (granulocyte-macrophage colony-stimulating factor) boosts immune cell production in the body. GMS may be used alone or given with other compounds.

Conclusion

Researchers must carefully evaluate which cancers are most suitable for a therapeutic vaccine approach. Generally, the cancers that are the best candidates are those whose treatments are associated with high costs and therapies that are less effective, or therapies that involve the risk of serious side effects for the patient.[14] Cancers such as lung cancer, pancreatic cancer, and breast cancer are such candidates for vaccine therapy. Much study, insight, and skill will be needed to develop these vaccines.

Thanks to Caitlin E. Lentz, PharmD, and others for reviewing this article. 


  1. American Society of Clinical Oncology. What are cancer vaccines? Accessed 04/19/2017.
  2. Berinstein, N.L., Spaner, D. Therapeutic cancer vaccines. In: Plotkin SA, Orenstein WA, Offit PA. Vaccines, 5th ed. Philadelphia: Saunders, 2008.
  3. Hosking, R. Cancer and the immune system. Cell. 2012;149(1):5-6. Accessed 04/19/2017.
  4. American Cancer Society. Cancer immunotherapy.  Accessed 04/19/2017.
  5. Goldman, B., DeFrancesco, L. The cancer vaccine roller coaster. Nature Biotechnology. 2009:27(2):129-140.
  6. Provenge prescribing information. (205 KB). Accessed 04/19/2017.
  7. Dana-Farber Cancer Institute. Provenge frequently asked questions. Available at Accessed 04/19/2017.
  8. Sharma, A., Koldovsky, U., Xu, S., Mick, R., Roses, R., Fitzpatrick, E., Weinstein, S., Nisenbaum, H., Levine, B.L., Fox, K., Zhang, P., Koski, G., Czerniecki, B.J. HER2-pulsed dendritic cell vaccine can eliminate HER-2 expression and impact DCIS. Cancer. 2012;118(17):4354-4362. Accessed 04/19/2017.
  9. Avigan, D.E., Vasir, B., George, D.J., Oh, W.K., Atkins, M.B., McDermott, D.F., Kantoff, P.W., Figlin, R.A., Vasconcelles, M.J., Xu, Y., Kufe, D., Bukowski, R.M. Phase I/II study of vaccination with electrofused allogeneic dendritic cells/autologous tumor-derived cells in patients with stage IV renal cell carcinoma. J Immunother. 2007;30(7):749-61.
  10. de Gruijl, T.D., van den Eertwegh, A.J.M., Pinedo, H.M., Scheper, R.J. Whole-cell cancer vaccination: from autologous to allogeneic tumor- and dendritic cell-based vaccines. Cancer Immunology, Immunotherapy. 2008;57(10):1569-1577.
  11. Morrow, M.P., Weiner, D.B. DNA drugs come of age. Scientific American. July 2010:48-53.
  12. See trials NCT00807781, NCT01493154, NCT00849121, and NCT01138410 on clinicaltrials.gov
  13. Cancer Research UK. Trastuzumab. Accessed 04/19/2017.
  14. Davis, M.M., Dayoub, E.J. A strategic approach to therapeutic cancer vaccines in the 21st century. JAMA. 2011;305(22):2343-2344

Last update 19 April 2017

Ebola Virus Disease and Ebola Vaccines

Ebola Virus Disease and Ebola Vaccines

Ebola virus disease (EVD) emerged at unprecedented epidemic levels in West Africa in 2014. Whereas previous EVD outbreaks were contained fairly quickly, this epidemic spread to crowded urban areas where transmissions continued unabated for many months.

Retrospective analysis indicates that the first case of the disease may have occurred at the end of 2013. An 18-month-old boy in a small village in Guinea became ill and died in late December, and the disease began to spread. It wasn’t until late March 2014 that the disease-causing agent was identified as Ebola virus. Through the fall of 2014, the epidemic was ongoing in Sierra Leone, Guinea, and Liberia. Nigeria and Senegal had small outbreaks related to importations from neighboring countries, but public health authorities there were able to contain spread of the disease. Several cases and deaths were reported from Mali, but spread was limited. In total, by the time the epidemic was over in March 2016, 11,325 confirmed, probable, and suspected deaths occurred. Total EVD cases numbered 28,652.

Transmission of the disease was limited to West African countries, with the exception of several transmissions in healthcare settings in Europe and the United States. Two U.S. nurses and one Spanish nurse became ill from contact with patients who acquired the disease in West Africa. The nurses recovered.

Ebola virus disease has no cure, but supportive care in a hospital setting can increase a patient’s chance for survival. Additionally, plasma transfusions from convalescent patients and an experimental antibody preparation have been used to treat certain patients. It is not possible to say at this time whether these treatments have had an effect on the course of the disease in the patients who received them.

Ebola virus was first identified in 1976. By the end of that year, two related strains of the virus were known–Ebola Zaire and Ebola Sudan. Three other strains are now known to exist. Vaccine development began in the late 1970s: results from a test of inactivated Ebola vaccine in guinea pigs were published in Lancet in 1980. Because EVD outbreaks are rare and have, until 2014, been controlled quickly, commercial vaccine manufacturers have demonstrated little urgency in advancing vaccines through clinical trials. That changed in 2014: several vaccines previously tested only in animals are being fast-tracked into Phase 1 clinical trials.

ClinicalTrials.gov, a global registry of trials involving human subjects, lists several Ebola vaccine trials in progress. Ebola Zaire is the strain of the virus that is responsible for the 2014 outbreak; accordingly, all of the vaccine candidates being advanced are designed to prevent that strain. If these vaccines work for Ebola Zaire, it is very likely that the same principles can be applied to the other strains.

The two front-running vaccine candidates are a GSK chimpanzee adenovirus vector vaccine (including several versions of it) and a Merck/NewLink Genetics recombinant vaccine. Both are being tested in a single Phase 2 trial in Liberia in those at risk for EVD. The trial is being run by NIAID/NIH and began recruiting participants in fall 2015.

The Ebola vaccine licensed by NewLink Genetics in Ames, Iowa, was originally developed by the Public Health Agency of Canada, which still holds intellectual property rights for it. The vector for this monovalent Ebola Zaire vaccine is an attenuated vesicular stomatitis virus — a virus, like rabies virus, in the Rhabdoviridae family. Vesicular stomatitis virus (VSV) can infect humans though this is a self-limited infection. A safe VSV vaccine for animals has been developed for animal use but it is not currently marketed in the United States.

The version of the GSK Ebola vaccine in the Phase 2 trial is monovalent and offers protection from Ebola Zaire only. This vaccine uses an adenovirus to deliver key Ebola antigens to human cells. Adenoviruses can cause a variety of diseases, but attenuated adenoviruses are safe and have been studied as vaccine vectors. A related bivalent (Ebola Zaire and Ebola Sudan) chimpanzee adenovirus vaccine is being tested in a Phase 1 trial at the NIH Clinical Center.

A vaccine candidate originating from Thomas Jefferson University’s Vaccine Center may advance to clinical trials in humans. This vaccine, developed by Jefferson’s Matthias Schnell, delivers Ebola antigens with an inactivated rabies virus vector. Versions of the vaccine, which have also delivered both Ebola Zaire and Ebola Sudan antigens as well as Marburg virus antigens, have been tested in macaques. Funding from the National Institute of Allergy and Infectious Diseases and the Department of Defense allowed production of a clinical lot of the vaccine for a potential Phase 1 trial.

Johnson & Johnson has a prime-boost Ebola vaccine in development. This two-phase strategy starts with direct exposure to DNA (the “prime”) followed by offering the same or similar antigen in a virus that does not replicate well in human tissue (“the boost”). This approach has been shown in a variety of settings to yield a robust immune response to the antigen of interest. The Phase 1 trial starts in January 2015 in the United States and Europe. The first dose of the vaccine uses a DNA vaccine that primes the immune system to make Ebola Zaire and Ebola Sudan surface proteins; the boost vaccine is based on a recombinant adenovirus vector that delivers an Ebola Zaire surface protein.

More Phase 2 and 3 vaccine trials are already being planned. In many cases, trial participants will be those at high risk of contracting the disease, such as healthcare workers and family members of people who have EVD.


Sources

Centers for Disease Control and Prevention. Outbreaks chronology: Ebola virus disease. Accessed 04/19/2017.

Gallagher, J. Millions of Ebola vaccine doses by 2015, WHO says. BBC. October 24, 2014.  Accessed 04/19/2017.

Honigsbaum, M. Ebola: the race to find a vaccine. The Guardian. October 25, 2014.  Accessed 04/19/2017.

Johnson & Johnson announces major commitment to speed Ebola vaccine development and significantly expand production. Press release. October 22, 2014.   Accessed 04/19/2017.

Lupton, H.W., Lamber, R.D., Bumgardner, D.L., Moe, J.B., Eddy, G.A. Inactivated vaccine for Ebola virus efficacious in guineapig model. Lancet. 1980;2(8207): 1294:1295.  Accessed 04/19/2017.

Morello, L. Millions of doses of Ebola vaccine to be ready by end of 2015. Scientific American. October 27, 2014.  Accessed 04/19/2017.

Patane, M. NewLink moving ahead with Ebola vaccine trials. Des Moines Register, October 20, 2014. Accessed 04/19/2017.

Pollack, A. Vaccine trials for Ebola are planned in West Africa. New York Times. October 23, 2014.  Accessed 04/19/2017.

University of Maryland School of Medicine begins Ebola vaccine trial in Mali.  Accessed 04/19/2017.

U.S. National Institutes of Health. Phase 1 trial of Ebola vaccine in Mali   Accessed 04/19/2017.

U.S. National Institutes of Health. A study to assess a new Ebola vaccine, cAD3-EBO Z.  Accessed 04/19/2017.

World Health Organization. Origins of the 2014 Ebola Epidemic.  Accessed 04/19/2017.

Last update 19 April 2017

Cholera

Cholera

Symptoms and Causative Agent

Cholera is a diarrheal illness caused by an infection of the intestine by the Vibrio cholerae bacterium.

In about 80% of cholera infections, the person will have no symptoms or very mild symptoms. However, about 20% of people with symptoms will will experience profuse watery diarrhea, vomiting, and leg cramps.

Symptoms can occur within two hours to five days after initial exposure to V. cholera. 

Transmission

Cholera is transmitted by ingesting food or water contaminated with V. cholerae. The contamination occurs when fecal matter from a sick person comes into contact with food or water supplies.

In areas with poor environmental management and overcrowding, the risk of cholera increases dramatically. Ensuring that food and water supplies are clean and well managed is the easiest way to prevent the spread of cholera. The development and use of piped water systems, chlorination facilities, water filtration, safe water storage containers, and proper sewage disposal have helped reduce the spread of cholera.

Cholera is typically not spread directly from one person to another.

Treatment and Care

People who are ill with cholera can be treated with oral rehydration fluids. Intravenous fluids may be administered if the patient is severely dehydrated.

Antibiotics may be used to reduce the severity of symptoms. However, widespread use of antibiotics in areas with many cases of cholera is generally not recommended. Antibiotics do not prevent spread of the disease, and they may lead to V. cholerae’s increasing antimicrobial resistance.

Complications

In extreme cases of cholera, diarrhea can be so profuse that severe dehydration sets in, which can lead to sunken eyes, cold skin, decreased skin elasticity, wrinkling of the hands and feet, and a bluish tint to the skin.

Death can occur within hours of symptom onset if the patient does not receive treatment.

Available Vaccines and Vaccination Campaigns

Several oral cholera vaccines are available globally. The vaccines provide about 65%-85% protection from clinically significant cholera for a period of time from 4 months after vaccination to up to 5 years after vaccination, depending on the vaccine. Because vaccine effectiveness is somewhat low and short-term, cholera vaccines are used mainly for outbreak control and emergency use, rather than for routine vaccination.

U.S. Vaccination Recommendations

Cholera vaccination is not routinely recommended in the United States. Water-related spread of cholera bacterium has been eliminated in the United States due to modern water and sewage treatment systems.

U.S. residents who travel to an area with epidemic cholera (that is, parts of Africa, Asia, or Latin America) should consult a travel physician about cholera vaccination. An oral cholera vaccine (Cholera Vaccine, Live, Oral, [Vaxchora® ]) is approved for adults age 18-64 traveling to cholera-afflicted areas. Travelers to such areas are also advised to practice simple safeguards, such as drinking only bottled water and washing hands frequently.


Sources

Centers for Disease Control and Prevention. Cholera-Vibrio cholerae infection. Accessed 04/12/2017.

Centers for Disease Control and Prevention. Cholera vaccines. Accessed 04/12/2017.

Centers for Disease Control and Prevention. Infectious diseases related to travel: cholera. Accessed 04/12/2017.

U.S. FDA. VAXCHORA prescribing information. (563 KB). Accessed 08/16/2017.

World Health Organization. Cholera fact sheet. Accessed 04/12/2017.

Last update 16 August 2017

Typhoid Fever

Typhoid Fever

Symptoms and Causative Agent

Typhoid fever is a bacterial disease caused by Salmonella typhi. While rare in industrialized countries, typhoid fever is a significant threat in some low-income countries.

Symptoms of typhoid fever range from mild to serious and usually develop one to three weeks after exposure to the bacteria. Symptoms include fever, headache, nausea, constipation or diarrhea, loss of appetite, and a rose-colored rash on the body.

Typhoid fever symptoms are similar to those of other common gastrointestinal illnesses. The only way to know that a person is ill with typhoid is to have their blood or feces tested for Salmonella typhi.

Transmission

Typhoid fever spreads from person to person via contaminated food and water. Transmission is via the fecal-oral route, meaning that contaminated feces (and sometimes urine) may enter water supplies or food supplies, which may then be consumed by and infect others.  Salmonella typhi lives only in humans; there is no animal reservoir for the bacteria.

About 21 million cases of typhoid fever and 220,000 deaths occur annually worldwide.

Treatment and Care

Typhoid fever is found more commonly in densely populated areas where water supplies are vulnerable to contamination. Good water sanitation methods and proper storage and handling of food and water can help prevent spread of S. typhi.

Antibiotics are the only effective treatment for typhoid fever. Most patients improve after beginning antibiotic treatment, especially if the disease is detected early.

Complications

Typhoid fever may lead to intestinal bleeding and perforation. This in turn can cause severe abdominal pain, nausea, vomiting, and sepsis. Surgery may be needed to repair the intestinal damage.

Less common complications that can occur are inflammation of the heart muscle, inflammation of the lining of the heart and valves, pneumonia, inflammation of the pancreas, meningitis, kidney or bladder infections, and delirium.

Available Vaccines and Vaccination Campaigns

Two typhoid vaccines are licensed for use in the United States; these are typically reserved for people traveling to areas where typhoid fever is common or for people who may come into direct contact with the disease.

Ty21a is a live, attenuated vaccine given in oral capsule form. Within the first two years of vaccination, the vaccine is moderately effective at preventing disease. Three years after initial vaccination, the vaccine offers no protection. The minimum age for this vaccine is six years.

Vi capsular polysaccharide (ViCPS) is an injected subunit vaccine. In clinical trials, it reduced disease rates by nearly 66%, though effectiveness wanes after several years. The minimum age for this vaccine is two years.

U.S. Vaccination Recommendations

Typhoid fever vaccination is neither required nor recommended for routine use in people who live in the United States. Vaccination with Ty21a or ViCPS may be recommended for travel to areas where there is a risk for typhoid infection. Travelers are usually advised to take the typhoid vaccine one to two weeks before departure.

Both Ty21a and ViCPS are approved by the World Health Organization for use to control endemic disease and to control outbreaks.


Sources

Anwar, E., Goldberg, E., Fraser, A., Acosta, C.J., Paul, M., Leibovici, L. Vaccines for preventing typhoid fever. The Cochrane Database of Systematic Reviews 1: CD001261. 2014. Accessed 04/12/2017.

Centers for Disease Control and Prevention. National Center for Emerging and Zoonotic Diseases. Typhoid Fever. Accessed 04/12/2017.

Centers for Disease Control and Prevention. Typhoid Fever Vaccination. Accessed 04/12/2017.

The Mayo Clinic. Typhoid Fever. Accessed 04/12/2017.

Szu, S.C. (November 2013). Development of Vi conjugate – a new generation of typhoid vaccine. Expert Review of Vaccines 12 (11): 1273–86. Accessed 04/12/2017.

World Health Organization. Typhoid Fever. Accessed 04/12/2017.

World Health Organization. Typhoid Fever Vaccines. Accessed 04/12/2017.