DTaP Vaccination Series

The DTaP vaccination series is an FDA-approved, five-shot vaccine for young children in the United States for protection against diphtheria, tetanus, and pertussis. DTaP stands for diphtheria, tetanus, and acellular pertussis, which are all common childhood diseases. In the US, Daptacel and Infanrix are the two types of DTaP vaccines, whereas other countries offer other variations. Both Daptacel and Infanrix consist of five shots that stimulate the immune system to protect a child against those diseases. Children vaccinated with DTaP may still end up getting one of the diseases, but they often present with milder symptoms than if they were not vaccinated. The general vaccination schedule for the five shot series is two months, four months, six months, fifteen to eighteen months, and four to six years of age. DTaP vaccination fully protects nine out of ten children against acquiring disease, contributing to a downward trend in diphtheria, tetanus, and pertussis cases in developing children in the US.

Diphtheria is a bacterial infection that causes inflammation in the nose and throat, leading to difficulty breathing. Tetanus is another bacterial infection that results in painful contractions in the neck and jaw muscles. Pertussis, commonly known as whooping cough, is a bacterial infection that causes violent coughing fits. Before widespread vaccination, US diphtheria cases in the 1920s averaged 206,000 cases per year, resulting in approximately 15,520 deaths. In the 1940s, tetanus cases in the US peaked at around 580 cases per year with 472 deaths. US pertussis cases in the 1940s reached 200,000 cases per year with 9,000 deaths, but decreased to several thousands of cases per year after vaccine distribution. As of 2010, both diphtheria and tetanus cases remain below thirty cases per year in the US. However, as of 2019, pertussis cases have been slowly rising, averaging around 20,000 to 50,000 cases per year.

Vaccines such as the DTaP series stimulate the immune system to confer immunity, which is protection against a certain disease. The vaccines work by introducing an antigen, which is a foreign protein that leads the host’s body to produce antibodies against a specific disease that carries that same antigen or one like it. If the host gets infected by that disease later on, their antibodies will then be able to fight against the infection and protect the host from disease. There are several types of vaccines. Inactivated vaccines, one of the most common types, contain killed bacteria, which is safer because the bacteria cause an immune response while not causing disease in the individual. Another common type of vaccine is a live, attenuated vaccine. Attenuated vaccines are generally more effective because they utilize living bacteria, which mimics a natural infection and leads to a stronger immune response. For some vaccines, after the first dose, immunity may not reach its maximum level, or it may also decrease over time. In those cases, individuals should receive booster doses to remain protected from disease. 

Vaccine development research for diphtheria, tetanus, and pertussis began in the early twentieth century. Emil von Behring, a researcher working in Germany, created one of the first vaccines for diphtheria in 1913. He experimented with different types of vaccines, and ultimately developed a vaccine using the toxin secreted by Corynebacterium diphtheriae, the bacteria that causes diphtheria. Behring termed the vaccine diphtheria antitoxin-toxin, or diphtheria AT. In his 1913 paper “Über ein neues Diphtherieschutzmittel” (About a New Protective Remedy against Diphtheria), Behring explains that the vaccine consists of the diphtheria toxin neutralized partially by diphtheria antibodies so that its toxicity diminishes to a safe level. A subsequent clinical trial in 1913 found that Behring’s diphtheria vaccine protected more than ninety-nine percent of vaccinated infants in the trial.

Meanwhile, Shibasaburo Kitasato, one of Behring’s colleagues working in Japan, had been studying Clostridium tetani, the bacterium that causes tetanus, since 1889. Kitasato developed one of the first pure C. tetani cultures, which means that he was one of the first to create a culture without any contamination, allowing other researchers to use the bacteria’s toxin in vaccine production. Then, in the early 1920s, researchers developed the first tetanus vaccine by inactivating the toxin with formaldehyde, a natural compound that reduced toxicity. World War II brought urgent need for the US to implement widespread administration of the inactivated tetanus vaccine to soldiers. As a result, the incidence of tetanus decreased approximately thirty-fold compared to incidences during World War I.

In 1934, Pearl Kendrick, a pertussis researcher based in Grand Rapids, Michigan, developed one of the first pertussis vaccines that went through large-scale clinical trials. She inactivated Bordetella pertussis, the bacterium that causes pertussis, by using thimerosal, a chemical compound that killed the bacteria. In Kendrick’s 1936 paper on her pertussis vaccine clinical trial, she states that only four out of 712 vaccinated children contracted pertussis, and they were all mild cases.

In the mid-1900s, Kendrick designed one of the first combination vaccines that combined protection for diphtheria, tetanus, and pertussis. As of 2024, researchers recognize Kendrick’s combination vaccine as a prototype for the current DTaP vaccine administered. Combination vaccines eliminate the need for multiple injections for multiple diseases, reducing the discomfort and inconvenience associated with vaccination to a minimum. First, in 1942, Kendrick created a vaccine that conferred immunity to pertussis and diphtheria. Then, in 1960, she developed a vaccine for diphtheria, tetanus, pertussis, and poliomyelitis. Poliomyelitis is another common childhood disease that affects the nervous system and can cause permanent paralysis. Both of those combination vaccines led to decreased incidence of disease in vaccinated individuals.

The primary difference between Kendrick’s 1960 combination vaccine and the DTaP vaccine used as of 2024 is that Kendrick used whole-cell pertussis, while the DTaP vaccine contains acellular pertussis. Whole-cell pertussis means that the vaccine consisted of inactivated bacterial cells, while acellular pertussis means that the vaccine only has parts of B. pertussis cells. Vaccines with whole-cell pertussis led to adverse side effects, including high fever, seizures, and neurological conditions. In 1974, Yuji Sato, a researcher working in Japan, devised the acellular pertussis component where he only incorporated pertussis toxin and filamentous haemagglutinin, which are only parts of B. pertussis, in a pertussis vaccine. Although less effective than the whole-cell vaccine, the acellular vaccine produced fewer side effects. The diphtheria and tetanus components of Kendrick’s combination vaccine and the DTaP vaccine are the same. Both vaccines contain tetanus toxoid and diphtheria toxoid, which are inactivated forms of the toxin secreted by the bacteria. Those toxoids can elicit an immune response and the production of antibodies.

As of 2024, children in the US receive either Daptacel or Infanrix for their DTaP vaccination series. Sanofi Pasteur manufactures the Daptacel DTaP vaccine, while GlaxoSmithKline manufactures the Infanrix DTaP vaccine. Both vaccines are FDA-licensed and have the same components, but at different concentrations. A clinical trial than ran from 2010 to 2014 in Wisconsin showed that Daptacel and Infanrix had similar efficacy rates in children. They also have similar recommended vaccination schedules. The US Centers for Disease Control and Prevention, or CDC, recommend a schedule of five doses timed at children aged two months, four months, six months, fifteen to eighteen months, and four to six years. For Daptacel, children should receive the fourth dose between fifteen to twenty months, as opposed to fifteen to eighteen months for Infanrix. Additionally, those who receive one brand of DTaP should continue getting that same brand for the remainder of their vaccination series. In terms of vaccines for groups other than children, adolescents and adults should receive one dose of Tdap every ten years. Tdap has the same components of DTaP, but at lower concentrations. DTaP has higher levels of antigen because its main purpose is to build immunity, while Tdap merely boosts existing immunity. In the US, the two brands of approved Tdap vaccines are Boostrix and Adacel.

In addition to DTaP, other forms of vaccination against diphtheria, tetanus, and pertussis are also available. Several FDA-approved combination vaccines in the US protect against those three diseases and additional ones. For example, Pentacel targets diphtheria, tetanus, pertussis, poliomyelitis, and Haemophilus influenzae type b, which is a life-threatening bacterial infection that affects the lining of the brain. Another combination vaccine, Vaxelis, protects against diphtheria, tetanus, pertussis, poliomyelitis, H. influenzae type b, and hepatitis B. Hepatitis B is a liver infection that results from the hepatitis B virus. Physicians sometimes use those combination vaccines interchangeably with the DTaP vaccines.

In 2012, pertussis cases in the US reached almost 42,000 cases, which was the highest number of cases in the previous fifty years. Because most of the cases occurred in infants and young children, the surge prompted researchers to perform multiple studies on the pregnant people receiving Tdap and any possible effects on the infant’s DTaP immunization response. During pregnancy, if the mother receives the Tdap vaccine, maternal antibodies can pass to the fetus through the placenta and protect the infant from disease for the first few months of life. One study performed by a group of physicians and researchers across the US in 2014 found that placental transfer of maternal antibodies during pregnancy hindered the infant’s ability to have strong production of antibodies after the first three doses of the DTaP vaccine. However, after the fourth dose, there was no significant difference in antibody responses to DTaP between infants who did or did not have maternal antibodies. Those results reaffirmed the CDC recommendation in 2012 for all pregnant people to receive the Tdap vaccination during pregnancy.

Low DTaP vaccination rates in the US can be attributed to infants not receiving the fourth shot in the series. Additionally, low rates for DTaP, which is part of a child’s primary immunization series, or vaccines that all children under the age of two should receive, have contributed to overall low primary immunization rates. Healthy People 2020, which is a statement by the US federal government on healthcare objectives, placed a target of eighty percent vaccination coverage on the primary immunization series. However, estimates in 2020 place the actual coverage rate at only 68.5 percent. Prior studies pinpoint the cause of the low vaccination coverage rate on the fourth dose of the DTaP vaccine, which physicians usually recommend between ages fifteen to eighteen months. One challenge for receiving the fourth dose of DTaP is that infants can technically receive it at twelve months if at least six months have passed since the third dose, which has led to some provider confusion on when to give the fourth dose. Another challenge is that if children do not receive their first three doses of DTaP on time, they are not eligible to receive the fourth dose at the standard one-year checkup visit. Infants do not routinely have a scheduled check-up visit with their physician at fifteen months, which is the recommended earliest timepoint for the fourth dose. Therefore, parents may not remember to bring their child to the physician on time for the fourth dose. Public health programs target those areas of concerns to improve coverage rates of primary immunization series.

According to the CDC, in 2020, diphtheria and tetanus incidences in the US were at their lowest point in history. There have not been many studies on the efficacy of tetanus and diphtheria toxoids, commonly used for inactivated vaccines, in a controlled clinical trial. Rather, the CDC estimates from the production level of antibodies that tetanus toxoid provides almost one hundred percent protection, while diphtheria toxoid provides approximately ninety-seven percent protection. Although pertussis cases have been increasing overall since the 1980s, they are still lower than rates before vaccines were widespread. According to the CDC, one of the reasons why pertussis cases are increasing is that the DTaP vaccine uses acellular pertussis. Although it is safer than whole-cell pertussis vaccines, acellular pertussis is less effective, and immunity wanes at a quicker pace. However, the CDC reports that if children receive all five doses on schedule, the DTaP vaccine is ninety-eight percent effective within the year and seventy-one percent effective for the next five years. In addition, if a pregnant person gets the Tdap vaccine during pregnancy, that protects seventy-eight percent of infants from contracting pertussis and ninety percent of infants from being hospitalized.

The DTaP vaccination series builds upon previous vaccine research for diphtheria, tetanus, and pertussis to provide immunity to children in a combination vaccine. In addition, its development and use have spurred adaptations of the combination vaccine that protect against additional diseases, including poliomyelitis, H. influenzae b, and hepatitis B. Vaccination development research has also taken the direction toward alternative methods of immunization such as transcutaneous immunization, or TCI. TCI methods utilize topical application of disease-specific antigens instead of the traditional needle injection. One study in 2012, “Clinical Study of Transcutaneous Vaccination Using a Hydrogel Patch for Tetanus and Diphtheria,” showed that TCI methods using an antigen patch produced a strong immune response against tetanus and diphtheria in study participants without any serious side effects. Researchers continue to study different ways to effectively immunize individuals against childhood diseases such as diphtheria, tetanus, and pertussis.