Editorial commentary: the effect of Tdap vaccination of pregnant women on the subsequent antibody responses of their infants.

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EDITORIAL COMMENTARY The Effect of Tdap Vaccination of Pregnant Women on the Subsequent Antibody Responses of Their Infants James D. Cherry Department of Pediatrics, David Geffen School of Medicine, University of California–Los Angeles (See the Major Article by Ladhani et al on pages 1637–44.) Tdap; pregnancy; antibody responses; United Kingdom; North America. During the 20th century, Bordetella per- tussis was extensively studied in animal models, and many toxins and protective antigens were described [1–3]. A leader in B. pertussis research was Margaret Pitt- man, who was at the National Institutes of Health/US Food and Drug Administra- tion (NIH/FDA) from 1936 to 1990. She published 2 articles on pertussis toxin (PT) and the concept that pertussis was a toxin- mediated disease [4, 5]. In the 1970s, there was great concern about diphtheria, teta- nus toxoids, whole-cell pertussis (DTwP) vaccines in many countries (including Sweden, West Germany, United Kingdom, and Japan) and their relationship to neuro- logical illness and brain damage. The views of Dr Pittman led to the idea that less re- actogenic acellular vaccines could be pro- duced. Yuji Sato, who trained at NIH/FDA and was influenced by Dr Pittman, retur- ned to Japan and developed the first Diph- theria, Tetanus and Pertussis (DTaP) vaccines [1]. His goal was to produce a Received 28 July 2015; accepted 3 August 2015; electroni- cally published 15 September 2015. Correspondence: James D. Cherry, MD, MSc, Distinguished Research Professor of Pediatrics, David Geffen School of Med- icine at UCLA, 10833 Le Conte Ave, MDCC 22-442, Los Ange- les, CA 90095-1752 (jcherry@mednet.ucla.edu). Clinical Infectious Diseases ® 2015;61(11):1645–7 © The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals. permissions@oup.com. DOI: 10.1093/cid/civ700 PT toxoid vaccine; however, the initial vaccines developed in Japan contained, in addition to toxoided PT, filamentous hemagglutinin (FHA), pertactin (PRN), and fimbriae 2 (FIM 2) in varying amounts. In the 1980s, a number of acel- lular DTaP vaccines were developed and phase 2 studies were carried out. In the early 1990s, 8 efficacy trials were carried out in Europe and Africa. The trial vac- cines contained different concentrations of 1 to 5 antigens. However, all of the vac- cines contained virtually no lipopolysac- charide, and they were less reactogenic than the DTwP vaccines that they were compared with. In their discussion, Ladhani and asso- ciates [6] state that in regard to pertussis, there are no pertussis antibody levels that correlate with protection. I believe this is not true. There are serologic correlates. However, since they did not support the concept of PT being the most important antigen, they have been generally ignored. Of the 8 efficacy trials carried out in the 1990s, only 2 were done in such a way that serological correlations could be deter- mined [7, 8]. One of those studies was done by our group in Germany and the other was done in Sweden. The studies were performed independently, but the findings were similar. However, the study in Sweden had more power because there were approximately 2½ times as many ex- posed children. It was found that if the exposed children had low levels of anti- body to PRN and/or to FIM 2 or FIM 2/3, they were protected approximately 70% of the time. In contrast, it was found that antibody to FHA had no protective role and antibody to PT in low levels played a minor role in the protection of these children aged 7 to 30 month. The next point to discuss is the role of transplacentally acquired antibodies in the protection of infants aged ≤2 months. Per- tussis toxin is made up of 2 subunits. The A subunit contains the ADP-ribosylating toxin and the bigger B subunit provides considerable efficacy against typical pertus- sis [1, 3]. The A subunit of PT is the cause of death in young infants [9–13]. PT (the A subunit) causes leukocytosis with lympho- cytosis, and it has been suggested that the aggregates of leukocytes in the small arteri- oles and veinules are responsible for irre- versible pulmonary hypertension, which leads to shock, organ failure, and death [9–13]. It is possible, however, that the leu- kocytosis is only a marker for the problem and not the direct cause. The adverse effect of PT on G proteins in the heart or lungs could possibly directly result in heart or re- spiratory failure [9, 10]. Nevertheless, small amounts of anti- body to the A subunit of PT will prevent death in infants although it will not pre- vent infection. Therefore, the prevention of deaths by maternal tetanus, diphtheria and pertussis (Tdap) immunization in EDITORIAL COMMENTARY CID 2015:61 (1 December) Downloaded from http://cid.oxfordjournals.org/ at University of California, Los Angeles on January 12, 2016 Keywords.