Elsevier

Vaccine

Volume 29, Issue 35, 11 August 2011, Pages 5932-5939
Vaccine

Immunogenicity of the reduced-antigen-content dTpa vaccine (Boostrix®) in adults 55 years of age and over: A sub-analysis of four trials

https://doi.org/10.1016/j.vaccine.2011.06.049Get rights and content

Abstract

Background

Older adults, especially those over 65 years, are at risk of more severe morbidity from diphtheria, tetanus and pertussis and may transmit pertussis to unvaccinated or not yet fully vaccinated infants, but data on their response to reduced-antigen-content tetanus, diphtheria and acellular pertussis (dTpa) vaccines are lacking.

Methods

A sub-analysis pooled immunogenicity results in 293 adults aged 55+ years (mean age 64.4 years) from four randomised, controlled clinical trials of dTpa vaccine (Boostrix®, GlaxoSmithKline Biologicals) with or without IPV co-administration, or dTpa-IPV (Boostrix® IPV).

Results

Seroprotective antibody levels were achieved by 82.8% for diphtheria and 94.5% for tetanus. For pertussis antigens, the booster response rate, defined as initially seronegative subjects [<5 EU/mL] reaching ≥5 EU/mL; or a ≥2-fold increase in antibody concentration if initially seropositive was 89.2% for pertussis toxoid, 95.8% for filamentous haemagglutinin and 94.5% for pertactin. Post-booster geometric mean concentrations (GMC) increased for all antigens. Post-booster anti-tetanus and anti-PRN GMCs tended to be higher in 55- to 64-year olds than in those aged 65+.

Conclusion

Larger numbers of subjects over 75 years are needed to better define responses in advanced age, but these data suggest that a single booster dose of dTpa or dTpa-IPV induces good immunological responses in most, and that these vaccines could be readily integrated into existing programmes.

Introduction

Neither infection with Bordetella pertussis, nor vaccination with currently available whole-cell or acellular pertussis (Pa) vaccines, provides life-long protection against pertussis disease [1], [2]. Infant vaccination programmes in place since the 1940s have been highly successful in reducing morbidity and mortality due to pertussis in children. Yet B. pertussis continues to circulate, causing considerable morbidity in older populations and putting vulnerable, unvaccinated infants at risk of life-threatening disease [3], [4], [5], [6], [7]. Preventing pertussis in adolescents and adults is therefore a goal of vaccination policy in a growing number of countries [8], [9], [10].

Reduced antigen content vaccines containing Pa components are suitable for booster vaccination of adults and have been shown to be immunogenic and well tolerated across a broad age range; from pre-school-age children to the elderly [11], [12], [13]. There are currently three broad strategies to vaccinate older populations against pertussis: administration of a pertussis booster dose to adolescents; vaccination of the general adult population; and vaccination of those in close contact with infants: including parents, grandparents and healthcare workers (so-called ‘cocooning’) [14] Each of these strategies has its limitations, not the least of which is achieving vaccination of the difficult-to-reach adult population. National recommendations for booster vaccination of adults with reduced antigen content diphtheria–tetanus–acellular pertussis vaccines (dTpa) exist in some countries including the United States, Australia, France and Germany. Cocooning is also recommended by these and other countries. No upper age limit for dTpa booster vaccination is generally specified, with the exception of the United States where vaccination of individuals aged 65 years and older is currently not recommended [15]. Application to extend the recommendation above 65 years of age is ongoing.

Older adults and the elderly stand to benefit from pertussis booster vaccination, although in this group dTpa vaccine immunogenicity is not well documented. Few studies have specifically explored the burden of pertussis disease in seniors. Although morbidity and mortality from pertussis are highest in infants, the incidence of hospitalisations and deaths due to pertussis increases with age in adults [16]. In a Canadian study, individuals >50 years of age, presenting with pertussis developed pneumonia in 9% of cases and required hospitalisation in 6% of cases [17]. In Australia, pertussis notifications in individuals over 60 years old increased between 1995 and 2005, with a reported incidence in 2005 of around 75/100,000, a rate higher than in any other adult age group [18]. Serological studies point to pertussis infection in seniors and outbreaks in aged care facilities [19], [20], [21]. Older adults are unlikely to have received pertussis vaccination during childhood, and the limited available data suggest that immune responses to dTpa in individuals over 40 years tend to be lower than the immune response observed in younger age groups [22], [23], [24], [25].

Given this lack of available data, a post-hoc, pooled analysis was conducted on the subgroup of adults aged 55 years and older who participated in clinical trials of Boostrix® (GlaxoSmithKline [GSK] Biologicals, Belgium) or Boostrix®IPV (GSK Biologicals) to generate indicative data on the immunogenicity of dTpa in older adults. This evaluation may assist policy makers and clinicians considering the merits of pertussis prevention in the older adult population.

Section snippets

Methods

Subjects were healthy adults aged 55 years and over (55+ years) who had participated in one of four clinical trials of dTpa (Boostrix®) or dTpa-inactivated polio virus vaccine (dTpa-IPV, Boostrix® IPV). The results of each individual study (002, 003a, 003b and 034, Table 1) have been previously published [22], [26], [27], [28].

All four studies were randomised controlled trials designed to evaluate the immunogenicity and safety of dTpa and/or dTpa-IPV compared to licensed control vaccines, in

Demographic characteristics

A total of 312 age-eligible subjects were included in the four studies. Of these, 293 subjects were included in the ATP analysis of immunogenicity, including 166 adults aged 55–64 years and 127 adults aged 65+ years (Table 2). The mean ages of subjects who received their last diphtheria and/or tetanus dose 5–10 years, 10–20 years or >20 years previously, were within the same range (60–65 years, Table 3).

Diphtheria and tetanus

A substantial percentage (54.8% for diphtheria and 46.6% for tetanus) of 55+ year old

Discussion

A single dose of dTpa (Boostrix®) or dTpa-IPV (Boostrix® IPV) induced good humoral immune responses to the diphtheria, tetanus and pertussis vaccine antigens. While antibody GMCs for tetanus and PRN were reduced in adults aged 65+ years compared with adults aged 55–64 years, GMCs increased substantially (by at least 5.5-fold) from baseline for all antigens, indicating that all adults aged 55+ years can be vaccinated successfully. Of note, antibody GMCs against PT, FHA and PRN in both age strata

Acknowledgements

P.V.D., P.M. (delegate of Professor M. Burgess post-retirement) and E.G. were principal investigators and conducted the studies presented here. P.V.D., P.M. and E.G. made substantive contributions to the nature and interpretation of sub-analyses of the data, including the presentation of the results and discussion of the study findings. The sub-analyses were performed by S.M. Imran Hashmi, Devayani Kolhe, and SK who are statisticians at GSK Biologicals. Dr. Joanne Wolter (independent medical

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