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
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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