Studies of glycoconjugate vaccines have traditionally used an immune challenge with a plain polysaccharide vaccine to demonstrate immunologic memory. Plain polysaccharide vaccines are poorly immunogenic in children and can induce subsequent immunologic hyporesponsiveness. We therefore assessed the use of glycoconjugate vaccines as an alternative method of demonstrating immunologic memory.
Children immunized with hepatitis B vaccine or serogroup C meningococcal glycoconjugate vaccine (MenCC) at age 2, 3, 4 months received a plain polysaccharide meningococcal serogroup A/C vaccine (MenACP) or MenCC at age 12 months. A post hoc analysis of serum bactericidal activity responses to MenCC assessed whether this differed in MenCC primed and MenCC naive infants.
MenCC primed children displayed higher geometric mean serum bactericidal titers than MenCC naive children following MenACP (1518 compared with 30; P = 0.003). A similar difference was seen after a dose of MenCC to toddlers (MenCC primed: 8663, MenCC naive: 710; P < 0.001). The latter comparison became a borderline significance after adjusting for higher pretoddler immunization serum bactericidal geometric mean titers in the MenCC primed group (P = 0.068).
Administration of glycoconjugate vaccines provides an important alternative method of demonstrating immunologic memory, avoiding the use of plain polysaccharide vaccines that are potentially deleterious in children. This has implications for the design of all future clinical trials of glycoconjugate vaccines.
From the *Department of Paediatrics and †Department of Zoology, University of Oxford, Oxford, UK; ‡Emergent Biosolutions, Wokingham, Berkshire, UK; and §Centre for Statistics in Medicine, Oxford, UK.
Supplemental Digital Content is available for this article. Direct URL citations appear in the printed text; simply type the URL address into any Web browser to access this content. Clickable links to the material are provided in the HTML text and PDF of this article on the Journal's Web site (www.pidj.com).
Accepted for publication July 9, 2008.
Supported by the Thames Valley Comprehensive Clinical Research Network and the Oxford Partnership Comprehensive Biomedical Research Centre with funding from the Department of Health’s NIHR Biomedical Research Centres funding scheme.
The views expressed in this publication are those of the authors and not necessarily those of the Department of Health.
Dr. Snape has received financial assistance from Wyeth Vaccines Research, GlaxoSmithKline, and Novartis Vaccines to attend conferences and has had travel and accommodation expenses paid by Novartis Vaccines while working with Novartis Vaccines in Siena, Italy.
Dr. Pollard acts as chief investigator for clinical trials conducted on behalf of Oxford University, sponsored by vaccine manufacturers (Novartis Vaccines, GlaxoSmithKline, Sanofi-Aventis, Sanofi-Pasteur MSD, and Wyeth Vaccines Research), and has received assistance from vaccine manufacturers to attend scientific meetings.
Industry-sourced honoraria for lecturing or writing are paid directly to an independent charity or an educational/administrative fund held by the Department of Pediatrics, University of Oxford.
Dr. Lockhart was an employee of Wyeth Vaccines Research when the study was conducted and analyzed and this publication first drafted.
Address for correspondence: Matthew Snape, FRCPCH, Oxford Vaccine Group, CCVTM, Churchill Hospital, Old Rd, Headington, Oxford, OX3 7LJ. E-mail: email@example.com.