Combined reduced-antigen-content diphtheria–tetanus–acellular pertussis and polio vaccine (dTpa-IPV) for booster vaccination of adults

Abstract

Many countries recommend diphtheria, tetanus and/or poliomyelitis boosters in adolescents or adults and the need for pertussis booster vaccination beyond childhood is increasingly recognized. A new combined reduced-antigen-content dTpa-IPV vaccine provides booster vaccination against all four diseases in one single injection. The immunogenicity and safety of the dTpa-IPV vaccine was compared to that of licensed dTpa + IPV or Td-IPV vaccines in 806 adolescents >14 years of age and adults with a heterogeneous vaccination history. The dTpa-IPV vaccine was immunogenic and well tolerated. No clinically significant differences were observed between groups. Anti-tetanus antibody kinetics indicated that each of the vaccines could be used for tetanus prophylaxis in acute wound management. For all vaccines, the lowest post-vaccination antibody concentrations were observed in subjects >40 years of age, those seronegative prior to vaccination and those subjects whose last vaccination was ≥20 years ago. In conclusion, dTpa-IPV vaccination of subjects over 14 years of age was as immunogenic and well tolerated as the licensed dTpa + IPV or Td-IPV vaccines. Vaccination coverage of adults is poor and the use of combined vaccines such as dTpa-IPV during vaccination visits, or for wound management, maximizes opportunities for boosting in these difficult to reach age groups.

Introduction

Immunity against Bordetella pertussis disease wanes after both vaccination and natural infection [1], [2]. Although the incidence of pertussis in young children has decreased markedly since initiation of infant immunization programs, disease rates in older children, adolescents and adults in immunized populations are increasing [1], [3], [4]. In these age groups, pertussis results in considerable morbidity, but rarely leads to hospitalization or death [5], [6]. However, in parallel to increased disease in older age groups, increasing morbidity and mortality due to pertussis among infants is also reported in countries with high early childhood DTP vaccination coverage [7], [8], [9]. Although anti-pertussis antibodies may cross the placenta, circulating maternal antibodies on their own are not sufficient or do not reach levels that are high enough to result in passive protection after birth [10]. As a consequence, pertussis disease in young infants is often serious and life threatening, and the vast majority of deaths due to pertussis occur in infants too young to be fully immunized [11], [12], [13], [14], [15]. In a retrospective study in French paediatric intensive care units [14], pertussis was shown to be the first cause of mortality by bacterial infections in infants between 10 days and 2 months of age. Parents and older siblings have been identified as an important source of pertussis infection to unimmunized or partially immunized infants [14], [16], [17]. Therefore, vaccination of adolescents and adults against pertussis should provide a double protection: direct protection to vaccinees and indirect protection (herd immunity) to the at-risk infants with whom they are in contact.

Licensure of acellular pertussis vaccines with improved adverse event profiles compared to whole-cell pertussis combinations has allowed vaccination of older children and adults against pertussis for the first time [18], [19]. However, despite recognition that active prevention of pertussis in older populations is needed, until now, recommendations for pertussis boosting of older age groups only exist in a minority of countries [16], [20]. In addition, vaccination coverage in older age groups is generally poor even for well established antigens like diphtheria and tetanus for which regular vaccinations are necessary throughout life [21], [22], [23], [24] or polio that may be recommended during adolescence or adulthood in certain countries [22], [23], [25]. Vaccination coverage could be improved by the availability of combined vaccines that provide booster vaccination with all recommended antigens in a single injection [26]. GlaxoSmithKline (GSK) Biologicals has developed a combined reduced-antigen-content diphtheria and tetanus toxoids, acellular pertussis and poliomyelitis (dTpa-IPV, Boostrix^® Polio) vaccine. This study evaluated the immunogenicity and reactogenicity of a booster dose of dTpa-IPV in an adult population with a heterogeneous vaccination history, compared to licensed comparator vaccines.