A randomised controlled trial with a diphtheria–tetanus–acellular pertussis (dTpa) vaccine in adults
Introduction
Universal infant immunisation against diphtheria, tetanus, and pertussis is one of the major goals of the World Health Organisation (WHO) Expanded Programme on Immunisation (EPI). Diphtheria–tetanus–pertussis (DTP) primary vaccination of infants followed by a booster dose in the second year of life is almost universal practice [1]. In many countries, immunity to diphtheria and tetanus is currently maintained by booster vaccination at 5- to 10-year intervals. A reduced-antigen content diphtheria–tetanus (Td) vaccine is used in order to improve tolerability while eliciting an adequate immune response. However, pertussis vaccine boosters have not been recommended after seven years of age, mainly due to the high reactogenicity of traditional whole-cell vaccines in older children and the belief that pertussis was both uncommon and mild in older children, adolescents, and adults.
In the pre-vaccination era, pertussis infection commonly occurred in early life. The subsequent natural immunity was then maintained by periodic exposure to the organism (Bordetella pertussis) which acted as a natural booster [2]. Although the incidence of pertussis in young children has been markedly reduced following the successful implementation of infant immunisation programs, there has been a subsequent increase in the incidence in adults and adolescents [3], [4], [5], [6]. Indeed, vaccine-induced immunity to pertussis wanes, leaving older children, adolescents and adults susceptible to reinfection [3], [7], [8], [9], [10]. The major cause for concern is the potential for older infected individuals to serve as reservoir of infection to young infants [7], [8], [9]. Furthermore, because the symptoms are generally atypical in adults [11], adult infection is often difficult to diagnose [12] and this situation creates the potential for further spread. In addition, treatment with antibiotics is only effective within the first three weeks after onset of symptoms [13].
All these factors have prompted the development of a suitable vaccination strategy for older populations. This in part has been facilitated by the availability of acellular pertussis vaccines which are less reactogenic than whole-cell vaccines [14], [15]. Although combined diphtheria–tetanus–pertussis (DTPa) vaccines have become routine paediatric vaccines in many developed countries, their reactogenicity increases with successive doses, making the paediatric formulation less suitable for older individuals [16]. However reducing the content of the acellular pertussis antigens and formulating it with an established adult Td booster vaccine could result in a new candidate combination vaccine with improved tolerability and the potential to boost titres against all three diseases.
The purpose of this study was to assess the reactogenicity and immunogenicity of a diphtheria–tetanus–acellular pertussis candidate vaccine with reduced antigen content for diphtheria and pertussis (dTpa) in comparison with a standard, licensed adult reduced-antigen-content diphtheria–tetanus (Td) vaccine and an experimental candidate monovalent acellular pertussis vaccine with reduced antigen content (pa), respectively. The dTpa and pa vaccines had identical pertussis antigen content.
Section snippets
Subjects
This single (assessor) blinded, parallel group study was conducted at the Centre for the Evaluation of Vaccination, Epidemiology and Community Medicine, University of Antwerp, Belgium. The protocol was approved by the “Commissie voor Medische Ethiek”, Universitair Ziekenhuis Antwerpen, on October 2, 1997. Written informed consent was obtained from all subjects prior to enrolment. The trial was conducted in accordance with the Declaration of Helsinki and Good Clinical Practice in operation at
Results
Of the 299 subjects enrolled, all but three completed the study. Two were lost to follow-up and one subject withdrew his consent (not due to an adverse event). In the study cohort the male/female ratio was 147/152; the mean age was 30.1 years (range: 18–73 years). There were no statistically significant differences in these parameters between groups.
Discussion
Vaccination of adolescents and adults against pertussis is now being proposed by some authorities in order to manage the recently observed epidemiological shift in the incidence of the disease to older age groups [3]. In order to achieve continuous protection, it is probable that subsequent doses of pertussis vaccine are required at regular intervals throughout life, irrespective of both past immunisation history and exposure to the natural infection [30]. As it is the case for most
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