Pertussis: a Tale of Two Vaccines
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MILESTONES MILESTONE 8 vaccine. There had always been resistance to the whole-cell vaccine in Japan, and, persuaded that the side Pertussis: a tale of two vaccines effects were caused by products such as lipopolysaccharide and endotoxins The whole-cell pertussis vaccine present in the vaccine, he set out to causes rare but significant side effects. create a less reactogenic vaccine. By In addition to the usual local inflam- 1974 his team had succeeded in pro- matory effects and fever associated ducing an effective pertussis vaccine with many vaccines, whole-cell per- containing mainly just two antigens: tussis vaccines sometimes trigger pertussis toxin (PT) and filamentous prolonged crying and febrile haemagglutinin (FHA). This acellular convulsions and, very pertussis vaccine (aP) was shown to rarely, hypotonic–hypo- be effective, albeit less so than the responsive episodes. whole-cell vaccine, and in 1981 was Claims of causal approved for use in Japan. Other links to various countries adopted similar methods of neurological issues producing acellular vaccines, usually were also made. with added pertactin and type 2 and However, those type 3 fimbriae for better effectivity, neurological side and combined it to create the diph- effects were observed theria, tetanus, acellular pertussis vac- in very small numbers cine (DTaP). By the late 1990s, most of children and were high-income countries had switched later demonstrated to be to DTaP, although the cheaper DTwP Credit: Science Photo Library / Alamy Stock Photo Science Photo Library Credit: unrelated to the vaccine, but remains the vaccine of choice in low- Pertussis, or ‘whooping cough’, has the reputational damage was done. and middle-income countries. been identified since at least the The whole-cell pertussis vaccine This could be the end of the story, Middle Ages as a disease that affects By the early was blamed for causing various except that in countries using DTaP mostly infants and children, but 1980s, the intellectual and physical disabilities, there is now a resurgence in cases of whooping cough, with the char- can also affect teenagers and adults. introduction including in a TV documentary. The symptoms in the early stages of This precipitated the formation acteristic peak every 2–5 years that illness are similar to a cold, and then of pertussis of ‘Dissatisfied Parents Together’, was observed in the pre-vaccine era. develop into a characteristic cough vaccines was which would eventually become There are a number of hypotheses as accompanied with gasping breaths associated the National Vaccine Information to why this previously well-controlled (‘whoops’). It is highly infectious; early Center, and remains to this day a disease is now making a resurgence. 20th-century statistics claimed an with a large major source of disinformation about It has been suggested that the less- average death rate of 10% in children. decline in vaccines in the USA. effective long-term protection A therapeutic vaccine of uncertain cases Thousands of parents refused to (waning after 5–10 years) of DTaP efficacy was developed shortly vaccinate their children, and a flood has allowed the epidemic cycles to after the discovery of the causative of personal injury lawsuits forced re-establish themselves. This is partly agent, Bordetella pertussis, in 1906. many companies to stop producing challenged by more recent studies However, it was not until 1939 that vaccines. The US Congress passed that allege a long-lived, if imper- an effective preventive vaccine was the National Childhood Vaccine fect, protection afforded by DTaP. designed. Thanks to improved Injury Act, to protect vaccine man- Understanding of the transmission cultivation methods, Pearl Kendrick, ufacturers, which ironically is now and contact networks is incomplete, Grace Eldering and Loney Gordon used by vaccine deniers as ‘proof’ and studies looking at vaccine evasion developed a highly effective, whole- of the dangerous nature of vaccines. in B. pertussis are not conclusive. cell inactivated vaccine (wP). In the Three countries, Sweden, the UK In the meantime, several countries late 1940s the pertussis vaccine was and Japan, interrupted or decreased are experimenting with new vacci- combined with diphtheria and teta- pertussis vaccination. nation schedules and vaccination of nus toxoids to become DTP and was Meanwhile, in response to con- pregnant women, and the search for widely adopted shortly afterwards. cern about the side effects, Yuji Sato a better vaccine continues. By the early 1980s, the introduc- was working on an acellular pertussis Nicolas Fanget, npj Vaccines tion of pertussis vaccines was asso- ciated with a large decline in cases, ORIGINAL ARTICLES Kendrick, P. & Eldering, G. A study in active immunization against pertussis. Am. J. Hyg. 29B, 133–153 (1939) | Sato, Y., Arai, H. & Suzuki, K. Leukocytosis-promoting factor of Bordetella pertussis. 3. Its with incidence of whooping cough identity with protective antigen. Infect. Immun. 9, 801–810 (1974) in the USA decreasing 150-fold. FURTHER READING Boom, J. & Cunningham, R. Understanding and Managing Vaccine Concerns (Springer International Publishing Switzerland, 2014) | Cherry, J. The 112-year odyssey of pertussis and pertussis vaccines Unfortunately, as the risks from —mistakes made and implications for the future. J. Pediatric Infect. Dis. Soc. 8, 334–341 (2019) | de Cellès, M. D., whooping cough decreased markedly, Rohani, P. & King, A. A. Duration of immunity and effectiveness of diphtheria–tetanus–acellular pertussis vaccines attention shifted from the risk of in children. JAMA Pediatr. 173, 588 (2019) | Plotkin, S. A. The pertussis problem. Clin. Infect. Dis. 58, 830–833 (2013) | WHO. Pertussis vaccines. WHO position paper – September 2015. Wkly Epidemiol. Rec. 90, 433–458 (2015) disease to fear of vaccine side effects. S12 | NOVEMBER 2020 www.nature.com/collections/vaccines-milestone.