Pearl Luella Kendrick researched prevention for pertussis, commonly known as whooping cough, in Grand Rapids, Michigan, during the mid-1900s. Pertussis is a respiratory disease that mainly affects infants and young children. During the 1920s, pertussis was responsible for more deaths in children in the United States than any other disease. In the 1930s, Kendrick created one of the first pertussis vaccines that underwent large-scale clinical trials. Towards the end of her career, Kendrick helped developed combination vaccines for other common childhood diseases at the time, including diphtheria, tetanus, pertussis, and poliomyelitis. She also studied immune responses in infants whose mothers had pertussis antibodies that transferred to them during pregnancy. Kendrick helped lower the incidence and death rate of pertussis and other common childhood diseases in the US through the creation of vaccines.

Emil von Behring researched treatments for the common childhood disease diphtheria in Germany in the 1890s and early 1900s. Diphtheria is a lethal disease that infected approximately 40,000 people in Germany between 1886 and 1888 with a general mortality rate of twenty-five percent. Behring investigated treatment of diphtheria using serum therapy, which is an alternative to vaccination that uses protective agents from other people’s blood to defend a patient against disease. Behring termed those protective agents antitoxins. He received the first Nobel Prize in Physiology or Medicine for his work on serum therapy, which was one of the first Nobel Prizes given in the field of immunology. Additionally, Behring researched active vaccination as another way to protect patients from diphtheria. Behring’s studies lowered the mortality rate of diphtheria in Germany through serum therapy and vaccination, especially since vaccination confers protection to both mother and infant during pregnancy and after birth.

In 2014, Flor M. Munoz and colleagues published “Safety and Immunogenicity of Tetanus Diphtheria and Acellular Pertussis (Tdap) Immunization During Pregnancy in Mothers and Infants: A Randomized Clinical Trial,” hereafter “Tdap Immunization During Pregnancy,” in the Journal of the American Medical Association. The authors conducted a study to determine how Tdap immunization affected the mother and infant’s immune response to the common childhood diseases tetanus, diphtheria, and pertussis. They found that Tdap immunization did not lead to an increased risk of adverse health events. Furthermore, maternal Tdap immunization provided the infant with protective levels of pertussis antibodies after delivery and did not affect the infant differently from the DTaP vaccination series, which is the version of Tdap for young children. The authors’ findings in “Tdap Immunization During Pregnancy” supported the United States Centers for Disease Control and Prevention’s, or CDC’s, recommendation for pregnant women to receive the Tdap vaccine to prevent disease in mother and infant.

Germ-free, or GF, animals are laboratory animals that completely lack microbes, making them useful tools for microbiome research. Researchers create GF animals in laboratories by delivering the newborn animals in a way that protects them from microbes, which are microscopic organisms such as bacteria and viruses. They then house the GF animals in sterile conditions to ensure that the animals stay germ free. The creation of GF animals began in the late nineteenth century. Prior to that, scientists had no way to study the effects of the microbiome on overall health. The creation of GF animals allowed researchers to examine the microbiome under controlled conditions. They could colonize the animal with specific microbes and study their effects on the animal’s health without the confounding presence of other microbes. Researchers have used GF animals as a living model to study the microbiome, which has provided evidence for a relationship between the microbiome and health, including a role for the microbiome in shaping the development of multiple body systems.

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.

X-linked severe combined immunodeficiency, or X-SCID, is a chromosomal disorder in which the immune system lacks multiple protective cells that defend the body from disease. As of 2024, approximately one in 75,000 males have X-SCID. X-SCID is the most common type of SCID, which encompasses a range of disorders that all involve defects in immune cells that fight infections, leaving the individual susceptible to life-threatening diseases. X-SCID, which typically only affects males, arises due to a mutation in the interleukin 2 receptor gamma chain, or IL-2RG, gene on the X chromosome. IL-2RG aids certain immune cells to develop their protective functions, so a mutation in the receptor results in a dysfunctional immune system. Doctors most commonly use bone marrow transplants to treat X-SCID. By studying cases of X-SCID, researchers more clearly defined the role of lymphocytes in immune system development and overall disease protection. Unless detected and treated early, the defect in immune cells from X-SCID makes the individual prone to severe, recurrent infections, which are almost always fatal.

David Phillip Vetter was born with X-linked severe combined immunodeficiency disorder, or X-SCID, and spent most of his life in an isolated sterile bubble to stay alive. X-SCID is a genetic disorder that causes a deficiency of protective immune cells that fight infections, which increases susceptibility to disease. Vetter’s weakened immune system meant that he would die if he encountered any bacteria, viruses, or other germs, so his doctors placed him in a sterile isolator, a plastic bubble that prevented germs from entering. Vetter was thus a germ-free human, meaning he developed in the absence of germ exposure. He grew up in his sterile isolator, earning him the nickname “Bubble Boy,” and lived there until his death in 1984 at age twelve. Researchers frequently studied Vetter’s development because he was one of the first individuals with X-SCID to survive over a year after birth. As one of the first germ-free humans, Vetter provided an opportunity for researchers to study what happens when a human develops without germs and his cells helped them determine the genetic cause of X-SCID.

In 2016, researcher Thomas Gensollen and colleagues published “How Colonization by Microbiota in Early Life Shapes the Immune System,” hereafter, “Microbiota Shapes the Immune System,” in Science. The article reviews [what is known about?] how microbial colonization impacts immune development in newborns. Because the immune system protects the body from infection, an individual’s microbiome composition also affects susceptibility to certain diseases. Specifically, the authors discuss microbe colonization during early life, a time they refer to as the window of opportunity for future disease susceptibility. That window of opportunity is a period where environmental influences more easily shape the infant’s immune cells and their functions. In turn, the authors present that window as an optimal time for treating disorders associated with the microbiome and the immune system. “Microbiota Shapes the Immune System” reviewed data from dozens of articles to show that there is a narrow window during infancy where microbiome interactions directly or indirectly influence immune development, a potential area for interventional methods to target immune development.