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Can Meningococcal C Conjugate Vaccine Overcome Immune Hyporesponsiveness Induced by Previous Administration of Plain Polysaccharide Vaccine?
To the Editor: We previously reported a randomized controlled trial to assess the induction of immunologic memory in children (15-23 months) previously given 2 doses of either meningococcal C conjugate vaccine or plain quadrivalent meningococcal polysaccharide vaccine, separated by 2 months.1 The conjugate vaccination primed for a memory IgG antimeningococcal C antibody response to a dose of plain quadrivalent meningococcal vaccine given 1 year later.1 In contrast, the group initially given the plain meningococcal vaccine showed evidence of hyporesponsiveness. While the clinical significance is unknown, theoretically, these children might be at increased risk for invasive serogroup C meningococcal disease if exposed. Therefore, we carried out an open-label extension of the previous study at the 3 original sites to determine if a dose of meningococcal C conjugate vaccine could overcome this hyporesponsive state.
Methods
Children who had received either 2 doses of plain meningococcal vaccine 2 months apart followed by a third dose 1 year later (group 2) or had received 2 doses of hepatitis B vaccine and a dose of plain meningococcal vaccine 1 year later (group 3) were eligible for the extension study. The parents or legal guardians of these 129 eligible children were approached, and 98 (76%) gave authorization for participation (51/67 [76%] of group 2; 47/62 [76%] of group 3). Each child then received 1 intramuscular dose of the meningococcal C conjugate vaccine (lots AV95H30A and AV96D03; Chiron Corp, Emeryville, Calif). Clinical follow-up for local and systemic reactions was similar to the original study. Serum samples were obtained immediately before and 1 month after the immunization. The antibody assays were performed as previously described.1
Results
Of the 98 children enrolled in the extension study, 50 (98%) of 51 in group 2 and 47 (100%) in group 3 completed follow-up. The 2 groups were similar with respect to mean (SD) age at enrollment (both groups, 50 [3.3] months), male-to-female ratio (1.13 and 1.04, respectively), and ethnic background (90% and 96% white, respectively). The meningococcal C conjugate vaccine was well tolerated by both groups. The antibody responses to the conjugated meningococcal vaccine are summarized in Table 1. The conjugated meningococcal vaccine induced titers of bactericidal antibody considered to be protective ( 1:8) in the majority of subjects in both groups. However, at a mean age of 50 months, there was still evidence of immune hyporesponsiveness to the meningococcal C polysaccharide component among the children who previously had been found to be hyporesponsive at 34 months.
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Table. Serum ELISA and Bactericidal Responses to Immunization With Conjugated Meningococcal C Vaccine*
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Comment
The observation that previous administration of plain meningococcal polysaccharide vaccine to young children induces a hyporesponsive state to meningococcal C polysaccharide has been confirmed in multiple studies.1-3 We found that these children also are relatively hyporesponsive when given meningococcal C conjugate vaccine, and hyporesponsiveness can be detected 18 months after receipt of the last dose of the plain meningococcal polysaccharide vaccine. The molecular mechanism of this immune hyporesponse is unknown.
Evaluation of this phenomenon in children and adults with known terminal complement component deficiency who have previously received plain meningococcal quadrivalent polysaccharide vaccine may be important because these patients are at increased risk of recurrent meningococcal disease.
AUTHOR INFORMATION
Previous Presentation: Presented in part at the 1999 Annual Meeting of the Pediatric Academic Societies, San Francisco, Calif, May 1999.
Noni E. MacDonald, MD;
Scott A. Halperin, MD
Dalhousie University
Halifax, Nova Scotia
Barbara J. Law, MD
University of Manitoba
Winnipeg
Lisa E. Danzig, MD
Chiron Corporation
Emeryville, Calif
Dan M. Granoff, MD
Children's Hospital
Oakland Research Institute
Oakland, Calif
1. MacDonald NE, Halperin SA, Law BJ, Forrest B, Danzig LE, Granoff DM. Induction of immunologic memory by conjugated vs plain meningococcal C polysaccharide vaccine in toddlers: a randomized controlled trial. JAMA. 1998;280:1685-1689.
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2. Gold R, Lepow ML, Holdschneider I, et al. Kinetics of antibody production to group A and group C meningococcal polysaccharide vaccines administered during the first six years of life: prospects for routine immunization of infants and children. J Infect Dis. 1979;140:690-697.
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3. Leach A, Twumasi PA, Kumah S, et al. Induction of immunologic memory in Gambian children by vaccination in infancy with a group A plus group C meningococcal polysaccharide protein conjugate vaccine. J Infect Dis. 1997;175:200-204.
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Letters Section Editors: Phil B. Fontanarosa, MD, Deputy Editor; Stephen J. Lurie, MD, PhD, Fishbein Fellow.
JAMA. 2000;283:1826-1827.
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