Elsevier

Vaccine

Volume 23, Issue 29, 31 May 2005, Pages 3829-3835
Vaccine

Immunogenicity and reactogenicity of combined acellular pertussis/tetanus/low dose diphtheria vaccines given as a booster to UK teenagers

https://doi.org/10.1016/j.vaccine.2005.02.030Get rights and content

Abstract

Sustained high incidence of pertussis, particularly amongst unvaccinated infants, is of concern. Inclusion of pertussis vaccination with tetanus and low dose diphtheria (Td) teenage boosters may protect individuals through reproductive years, and prevent transmission to offspring. UK teenagers who had previously received only a three-dose primary course of whole cell pertussis vaccination in infancy and who were due to receive a Td booster (n = 323) were randomised to four groups: Td, TdaP, TdaP-inactivated polio vaccine (IPV) (Aventis Pasteur), TdaP (GlaxoSmithKline). There were significant pre- to post-vaccination GMC and GMFR increase for vaccine-contained pertussis antigens (p < 0.001) in recipients of aP-containing vaccine. All groups demonstrated significant increases pre- to 4 weeks post-vaccination in diphtheria (D)/tetanus (T) geometric mean concentrations (GMCs) and fold rises (GMFRs) (p < 0.001). Groups all achieved similar D and T post-vaccination GMCs. Local reactogenicity was generally similar between groups and was not associated with pre-booster diphtheria/tetanus antibody levels. A minority of vaccinees reported systemic symptoms with similar proportions between groups for each symptom assessed. This study demonstrated that addition of aP and/or IPV to Td vaccine did not materially alter reactogenicity or immunogenicity of Td components, and induced immune responses to pertussis antigens in teenagers who had received no pertussis vaccine since infancy.

Introduction

The role of whooping cough in adults in maintaining endemic transmission of Bordetella pertussis in populations with well-implemented infant vaccination programmes has been increasingly recognised in recent years [1]. Not only is pertussis an important cause of persistent cough in adults [2], [3], [4] but it may also be a source of infection for young infants in whom pertussis is a severe and potentially life threatening infection. A recent study in the US of infants with reported pertussis, over 70% had been infected by their mother or other family member, the majority of whom were aged 20 years or more [5]. Another study in UK infants admitted to paediatric intensive care with acute respiratory tract infection, apnoea and bradycardia showed that 20% had laboratory evidence of pertussis of whom half were infected from an adult family member [6].

Though pertussis vaccination of infants has significantly reduced disease incidence in children, vaccination does not provide long-term protection [7], [8] and most developed countries now give one or more booster dose after completion of the primary infant course. In the UK, a combined diphtheria, tetanus, acellular pertussis (DTaP) booster was added to the primary infant 2/3/4 month schedule in 2001 to be given at 3–4 years of age prior to school entry. However, countries already giving a pertussis vaccine booster at this age have seen rising numbers of cases in teenage years, so a second booster in adolescence may be indicated in the UK in the future, combined with the existing tetanus/low dose diphtheria/(Td) vaccine already given at this age. Use of wP vaccines would not be acceptable due to the high incidence of side effects such as local reactions and pyrexia [9]. Studies in adults with several aP vaccines have demonstrated immunogenicity and low reactogenicity when given either as a monovalent pertussis or combined with Td [10], [11], [12], [13]. In anticipation of the need to boost immunity to pertussis in young UK adults, a phase II trial with candidate TdaP vaccines in adolescents was conducted. A vaccine with inactivated polio vaccine (IPV) in place of oral polio vaccine (OPV) was included in anticipation of a change in the near future to IPV. Data on antibody responses and reactogenicity of the vaccines are reported.

Section snippets

Study design

This was a randomised, single blind phase II/III reactogenicity and immunogenicity study; (subjects were not informed of which vaccine they received).

Prior to enrolment subjects were screened for eligibility: inclusion criteria were informed written consent from student and parent/guardian; aged 13–17 years with evidence of receipt of ≥4 doses of DT-containing vaccine (three in infancy and a booster) with ≥8 years since the last dose. Exclusions were: contraindications to diphtheria, tetanus,

Results

In total, 323 subjects were recruited; 290 (90%) returned diaries and 288 (89.2%) provided paired serology samples. Proportions with paired samples ranged from 86–92% between groups (p = 0.74) (Table 2). Proportions returning diaries ranged from 87–93% between groups (p = 0.55) (Table 3). Overall the mean age at vaccination was 15.02 years (range 13.08–17.86 years) and the sex ratio was 0.98 (160M:163F); the age and sex distribution did not differ significantly between vaccine (p = 0.10 and p = 0.16,

Discussion

This study showed that replacement of the Td booster vaccine currently given to UK adolescents with a combined TdaP or TdaP-IPV vaccine would not materially increase the frequency of local or systemic post-vaccination symptoms, nor compromise the diphtheria and tetanus responses. Our findings are consistent with those of others who have compared in teenagers and adults the immunogenicity and reactogenicity of a Td and TdaP vaccine [19], or a Td-IPV and TdaP-IPV vaccine [20].

Despite the long

Acknowledgements

We thank the study nurses in Hertfordshire for the patient recruitment and follow-up, and Joan Vurdien and Teresa Gibbs for their help with study administration. We also thank Dr. David Salisbury Department of Health, London, for his help in funding this study (Grant number 1632/1905/63214) and Aventis Pasteur MSD for supporting the follow up of the TdPa/IPV group. We thank the reviewers for their helpful comments.

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