Elsevier

Vaccine

Volume 24, Issues 35–36, 28 August 2006, Pages 6120-6128
Vaccine

A comparison of booster immunisation with a combination DTPa-IPV vaccine or DTPa plus IPV in separate injections when co-administered with MMR, at age 4–6 years

https://doi.org/10.1016/j.vaccine.2006.05.017Get rights and content

Abstract

This study evaluated GSK's combined DTPa-IPV vaccine (Infanrix™-IPV) given as a fifth consecutive acellular pertussis booster dose in conjunction with the second dose of MMR vaccine (Priorix™) in children aged 4–6 years. The immunogenicity and reactogenicity of this vaccine regimen was compared with separate injections of DTPa and IPV when given concomitantly with MMR. A cohort of 362 children previously primed with four doses of DTPa and OPV, and a single dose of MMR were randomized to receive either DTPa-IPV + MMR (N = 181) or DTPa + IPV + MMR (N = 181). Antibody concentrations were measured prior to and 1 month after the booster dose. After immunisation all subjects from both groups had seroprotective antibody levels against diphtheria, tetanus and the three poliovirus serotypes, ≥96% showed vaccine response to PT, FHA and PRN, all were seropositive to mumps and rubella, and all but one subject were seropositive to measles. Immunogenicity results for each component antigen were similar for DTPa-IPV and separately co-administered DTPa and IPV. Local reactions were common with 24.0% and 31.1% of children experiencing swelling >50 mm at the DTPa-IPV and DTPa injection sites, respectively. The DTPa-IPV combination did not increase the incidence or intensity of adverse events compared with separately administered DTPa + IPV. The response to the concomitantly administered MMR vaccine was similar in the two groups and similar to previously reported responses for a second dose of MMR. This combined DTPa-IPV vaccine has a similar reactogenicity profile to DTPa, is immunogenic when given as a booster dose at 4–6 years of age, and has no impact on the immunogenicity of a co-administered second dose of MMR vaccine.

Introduction

A number of immunisation schedules now include a recommendation for inactivated polio vaccine to be administered to infants as “best practice” [1]. Inactivated polio vaccine (IPV) is increasingly preferred over oral polio vaccine (OPV) due to the very rare possibility of vaccine associated paralytic poliomyelitis (VAPP) in recipients of OPV and their contacts [1], [2]. In the USA, where 8–10 cases of VAPP were reported each year, IPV has been the recommended polio vaccine since 1997 [2]. In Europe, a number of countries have moved from using OPV to using IPV in the last decade, with IPV alone being now used in Austria, Belgium, Finland, France, Germany, Iceland, Luxembourg, Monaco and The Netherlands [3]. In the United Kingdom (UK), IPV was recently included in the routine immunisation schedule due to the relative increase in importance of VAPP as the number of cases of poliomyelitis due to wild virus decreased [4].

According to data from the Australian Childhood Immunisation Register (ACIR) [5], 99.2% of children in Australia, still receive OPV despite a recommendation for IPV (without provision of funding) since September 2003 [5]. IPV will be funded Federally for all Australian children from November 2005, but the successful implementation of this recommendation would be facilitated by the availability of suitable combination vaccines to avoid an increase in the number of injections provided at routine immunisation visits and a more cost-effective alternative to monovalent poliovirus vaccine. Combination vaccines, by reducing the number of injections given at each immunisation encounter, increase convenience of immunisations for both the vaccinees and immunisation providers [6], [7]. In doing so, they have the advantage of potential higher compliance with immunisation programs and reduction of their overall costs [2], [8], [9]. Administration of fewer vaccines simplifies storage and delivery logistics, fewer staff are required for immunisation delivery and the risk of immunisation related errors is reduced. There is evidence that some parents and immunisation providers are reluctant for children to have multiple injections at an immunisation encounter [6], [7]. This may result in delayed completion of immunisations with increased risk to the infant of acquiring a vaccine preventable disease [10]. Several IPV-containing combination vaccines are available, including a combined DTPa-IPV vaccine for primary and booster immunisation, but the impact of new combination vaccines on the immunogenicity and reactogenicity of other co-administered vaccines needs to be evaluated.

Provision of a pertussis containing vaccine prior to school entry is required to provide protection against pertussis infection and improve herd immunity in the population [11]. Previous studies have shown that large local reactions may occur with the administration of the fourth or fifth dose of a variety of DTPa vaccines. These reactions are more likely to occur when DTPa is provided for all primary and booster doses compared to a combination of DTPa and DTPw [12], [13], [14], [15], [16], [17], [18], [19]. Despite the increased incidence of large local reactions, swelling and discomfort usually resolve without sequelae. Rarely, swelling may involve the whole limb and may be associated with pain and limitation of movement.

In this study, the immunogenicity and reactogenicity of DTPa-IPV vaccine when administered as a booster at 4–6 years of age was examined and compared to DTPa and IPV administered separately. These vaccines were co-administered with measles, mumps, rubella (MMR) vaccine given as a second dose, prior to school entry. The aims of the study were to compare the safety and immunogenicity of the study vaccines administered in both groups and to assess the reactogenicity and immunogenicity of MMR vaccine 1 month after immunisation.

Section snippets

Methods

The study was an open, randomized phase IIIb, non-inferiority study conducted in three centres in Australia. Children free of obvious health problems and who had completed a primary vaccination course with DTPa and polio vaccines at 2, 4 and 6 months of age and had received a DTPa booster and immunisation for MMR in the second year of life were included in the study.

The study was approved by the individual hospital ethics committees at the three study centres, and was conducted in accordance

Study population

Three urban centres in Australia (Adelaide, Melbourne and Perth) enrolled a total of 366 healthy children 4–6 years of age (56% female) between May and December 2002 and 362 subjects received a dose of the study vaccine (four subjects were eliminated prior to receiving a vaccination as they did not fulfil the inclusion/exclusion criteria). Of the 362 subjects vaccinated, 360 subjects completed the study. One in each group withdrew from the study for reasons not related to adverse events. The

Discussion

In order to maintain high immunisation coverage rates at a time when there are increasing numbers of vaccines available for protection of children against infectious disease, combination vaccines are becoming an important priority in vaccine development [23], [24], [25]. However, antigens cannot be combined indiscriminately as each combination may affect the immunogenicity of the individual components. This has been seen, for example, with many of the Haemophilus influenzae type b combination

Acknowledgements

The authors are indebted to the following study staff: Mrs. Michelle Clarke, Mrs. Diana Weber, Mrs. Ria Halstead, Mrs. J. Aldis, Mrs. L. Dinan, Dr. Jan Walker, Dr. Rachel Chen, Dr. Sue Warcup, Dr. Margie Kummerow, Ms. Jacinta O'Sullivan, Ms. Susie Gabriel, Dr. Vanessa Johnston, Kelly Allen, Clare Brophy, Samantha Colquhoun, Jane Ryrie, Bernadette McCudden, Jane Nelson, Liz McGrath, Pamela Sinclair, Betty Lim, Ethna Macken, Dr. Phil Hoffman, Barb Sherry, Dr. Declan Green, Deborah Saunders, Jan

References (33)

  • M. Kraisinger

    Update on childhood immunization

    Am J Health-Syst Pharm

    (1998)
  • D.M. Salisbury et al.

    Immunization in Europe

  • ACIR: 002A National Report. Number of children who have received valid vaccinations between 01 January 2004–31 December...
  • N. Halsey

    Safety of combination vaccines: perception versus reality

    Pediatr Infect Dis J

    (2001)
  • C. Grant et al.

    Delayed immunization and risk of pertussis in infants: unmatched case–control study

    BMJ

    (2003)
  • R. Andrews et al.

    Pertussis notifications in Australia, 1991 to 1997

    CDI

    (1997)
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