Effects of Prior Polysaccharide Vaccination on Magnitude, Duration, and Quality of Immune Responses to and Safety Profile of a Meningococcal Serogroup C Tetanus Toxoid Conjugate Vaccination in Adults

Jo Southern

Sarah Deane

Lindsey Ashton

Ray Borrow

Immunisation Department, Communicable Disease Surveillance Centre, Health Protection Agency,^{Immunobiology Unit, Institute of Child Health,}^{Imperial College London and St Mary's Hospital, London,}^{Meningococcal Reference Unit, Health Protection Agency, Manchester,}^{Vaccine Evaluation Unit, Health Protection Agency, Gloucester, United Kingdom}⁴

^{Corresponding author. Mailing address: Immunisation Department, Communicable Disease Surveillance Centre, Health Protection Agency, 61 Colindale Ave., Colindale, London, United Kingdom. Phone: 44 (0) 208 200 6868. Fax: 44 (0) 208 200 7868. E-mail:}ku.gro.aph@nrehtuos.oj.

Received 2004 May 28; Revised 2004 Jul 21; Accepted 2004 Aug 26.

Abstract

Extensive use of meningococcal AC polysaccharide (MACP) vaccines has raised concerns about induction of immunologic hyporesponsiveness to C polysaccharide. We investigated the immunogenicity and safety of a meningococcal C-tetanus conjugate (MCC-TT) vaccine in naïve adults and prior MACP vaccinees. Laboratory staff (n = 113) were recruited; 73 were naïve to meningococcal vaccination, and 40 had previously received ≥1 dose of MACP vaccine. Blood was taken prior to MCC-TT vaccination and 1 week, 1 month, and 6 months later. At each time point, proportions of subjects with serum bactericidal antibody (SBA) titers of ≥8 or ≥128 were similar (P > 0.46); >94% of subjects achieved titers of ≥128 at 1 month. However, the geometric mean titer (GMT) of SBA at 1 month was higher in the naïve (1,757; 95% confidence interval [95% CI], 1,102 to 2,803) than in the previously vaccinated (662; 95% CI, 363 to 1,207) group (P = 0.02), and similarly at 6 months (P < 0.001). Conversely, geometric mean concentrations (GMCs) of serogroup C-specific immunoglobulin G (IgG) were significantly higher in the previously vaccinated group pre-MCC-TT and at 1 week; the groups were similar at 1 month, and there was some evidence that the GMC for the previously vaccinated group was higher at 6 months. Qualitative differences in antibodies between groups were demonstrated by using the SBA/IgG ratio, though avidity measures were similar for the two groups throughout the study. MCC-TT was well tolerated, with similar safety profiles in the two groups. Pain in the arm and headache were the most frequently reported events following vaccination. The study shows that MCC-TT is safe and immunogenic in naïve and previously MACP-vaccinated adults, though the magnitude and persistence of postvaccination SBA responses in the latter group were lower.

Abstract

Meningococcal serogroup C (MenC) disease is an important cause of morbidity and mortality worldwide. Until recently the only vaccines available against MenC were plain polysaccharide vaccines, which provide some protection but have two major disadvantages. First, they do not protect those aged ≤2 years, for whom the burden of disease is high (2, 24). Second, protection in older children and adults is short-lived, with no induction of immune memory (17).

Conjugation of meningococcal polysaccharide to immunogenic protein carriers has resulted in conjugate vaccines that induce T cell-dependent responses with higher antibody titers and increased antibody avidity as evidence of priming for immunologic memory, leading to better protection and longer-lasting immunity even in infants (8, 18, 21). In 1999, the United Kingdom became the first country to introduce MenC conjugate (MCC) vaccines formulated using mutant diphtheria toxin (MCC-CRM₁₉₇) or tetanus toxoid (MCC-TT) protein components, and these vaccines have been extensively used for infants, children, and young adults (16).

Reduced responses to repeated doses of MenC polysaccharide vaccine have been reported (12, 20), and the ability of an MCC-CRM₁₉₇ vaccine to induce immunologic responses adequate to confer protection has been demonstrated (4, 5). This study is the first to examine the effect of prior vaccination with plain serogroup C polysaccharide on acute responses to MCC-TT and on antibody persistence at 6 months postvaccination.

Acknowledgments

We thank the study nurses from Hertfordshire and Gloucester, the administrative staff at CDSC, and the laboratory staff at Manchester HPA and the Institute of Child Health for their work on this study. We thank personnel at the study sites who participated as well as those who assisted in the logistics and arrangements involved.

The study was jointly funded by the Department of Health (grant 121/7470) and the Health Protection Agency.

Acknowledgments

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