Elsevier

Vaccine

Volume 24, Issue 2, 12 January 2006, Pages 215-219
Vaccine

Immunogenicity of one, two or three doses of a meningococcal C conjugate vaccine conjugated to tetanus toxoid, given as a three-dose primary vaccination course in UK infants at 2, 3 and 4 months of age with acellular pertussis-containing DTP/Hib vaccine

https://doi.org/10.1016/j.vaccine.2005.07.060Get rights and content

Abstract

Reduction of the number of injections necessary to confer protection in the infant schedule would reduce discomfort, improve cost-effectiveness and create space for the addition of new vaccinations in the future. This study assessed the immunogenicity of one, two or three doses of meningococcal C conjugate vaccine conjugated to tetanus toxoid (MCC-TT) [Neis-VacC®] given concomitantly with a combined diphtheria/tetanus/acellular pertussis/Haemophilus influenzae type b -TT conjugate (DTaP-Hib-TT) [Infanrix-Hib®] vaccine at 2, 3 and 4 months of age. A total of 106 healthy UK infants were enrolled and randomised into two groups, one in which blood was taken after the first and third dose and the other after the second and third dose. The meningococcal serogroup C serum bactericidal antibody (SBA) geometric mean titre (GMT) rose significantly from post-first dose (491, 95% CI 275, 877) to post-second dose (1052, 95% CI 774, 1433) (p = 0.03), with no significant change after the third dose (1024, 95% CI 768, 1366). An SBA titre of ≥8 was achieved by 92% after the first dose and 100% after the second and third doses.

The Hib IgG geometric mean concentration (GMC) rose significantly after each dose: post-first (0.14 μg/ml 95% CI 0.10, 0.18), post-second (0.54 μg/ml, 95% CI 0.33, 0.90), post-third (2.04 μg/ml, 95% CI 1.52, 2.74). The Hib GMC after the third dose was higher than reported previously when this DTaP/Hib was given either on its own or concomitantly with a MCC-CRM conjugate vaccine according to the UK 2, 3 and 4 month schedule. This suggests some enhancement of the response to a Hib-TT vaccine by concomitant administration of MCC-TT.

These results suggest that a reduced number of doses of MCC-TT would be adequate in infancy if given concomitantly with an acellular pertussis-containing vaccine.

Introduction

Meningococcal C conjugate vaccine (MCC) has been routinely given a three-dose primary immunisation schedule at 2, 3 and 4 months of age to UK infants since November 1999 following successful pre-licensure trials with candidate vaccines [1], [2], [3]. These trials showed that the three candidate vaccines, which were conjugated to either to tetanus toxoid (TT) or CRM proteins, were highly immunogenic with 98–100% of infants achieving a serum bactericidal antibody (SBA) titres ≥8 after the second dose. This SBA titre has now been established as a correlate of short term protection for MCC vaccines [4], [5]).

Subsequently, the manufacturer of the MCC-TT initiated a study to investigate the immune response and induction of immunological memory following either one, two or three doses of MCC-TT. The percentage of infants with a SBA titre ≥8 1 month after their primary series was 98.4, 100 and 99.4% after the one-, two- and three-dose schedule, respectively [6]. This led to licensure of the MCC-TT vaccine as a two dose schedule 2 months apart, but data supporting this indication were based on the concomitant administration of DTP-Hib vaccine containing a whole cell pertussis component (DTwP/Hib) [6].

In a separate study, the response to MCC-TT was found to be significantly lower when given concomitantly with a DTaP/Hib/inactivated polio (DTaP/Hib-IPV) vaccine (Pediacel®) than with a DTwP/Hib vaccine [7], suggesting that a two dose schedule for MCC-TT may not be adequate if given with a DTaP/Hib-containing vaccine. This study is the first to report immunological responses following one, two or three doses of MCC-TT when given concomitantly with a DTaP/Hib vaccine (Infanrix-Hib®).

Section snippets

Study population

Infants aged 49–72 days old were recruited from general practices in Hertfordshire between January and August 2003. The following exclusion criteria were applied: receipt of any investigational or non-registered drug or vaccine, and or immunoglobulin or blood product since birth, or planned use during the study period; chronic administration (>14 days) of immunosuppressants or other immune-modifying drugs since birth (for corticosteroids 0.5 mg/kg/day, inhaled/topical steroids were allowed);

Study population

A total of 106 subjects were recruited, 53 in each group. Blood samples were obtained from 51 and 49 infants in group 1 after the first and third dose, respectively, and from 51 infants in group 2 after both the second and third doses. For some samples, results were not obtained because serum volumes were too small to complete the full array of testing.

The mean age at first vaccination for both groups was 0.165 years (60.3 days). The M:F ratios, 26:27 (0.96) in group 1 and 23:30 (0.77) in group

Discussion

This study indicates that a two dose primary schedule for MCC-TT vaccine would be sufficient for primary immunisation, starting at 2 months of age with an interval of 1 month between doses, and given concomitantly with a DTaP/Hib vaccine. Data were collected in this way in order not to disturb the established 2, 3 and 4 month routine vaccination schedule and to provide information on the most immunologically challenging situation. All infants achieved an SBA titre of ≥8 after the second dose and

Acknowledgements

We wish to thank the Vaccine Research Nurse team in Hertfordshire, the laboratory teams at Porton and Manchester and the administrative team at the Centre for Infection for their assistance in the conduct of the study. We wish to thank the Department of Health Research and Development Directorate for the provision of financial support of the study under grant number 1217470.

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