Kinetics of immune responses to nasal challenge with meningococcal polysaccharide one year after serogroup-C glycoconjugate vaccination

James B. Wing, Lynne Smart, Raymond Borrow, Jamie Findlow, Helen Findlow, Andrew W. Heath, Robert C. Read

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12 Citations (Scopus)

Abstract

Background. Recipients of serogroup-C glycoconjugate meningococcal vaccine (MCC) exhibit waning of serum bactericidal antibody (SBA) titers, but the rate of decline and the speed of their immunological memory in response to new meningococcal nasopharyngeal colonization are unknown. Methods .In a prospective challenge study, we measured persistence of SBA and anti-Neisseria meningitidis serogroup-C (MenC) immunoglobulin (Ig) G and IgA in adults aged 18-39, 28 days and 12 months after receiving MCC. Volunteers were then challenged intranasally with 50 μg MenC polysaccharide to mimic meningococcal colonization, and systemic and mucosal antibody responses were measured. Results .All subjects had protective SBA titers (≥8) 28 days after MCC vaccination, but 12.3% and 20.2% had unprotective (<8) or low (<128) levels, respectively, after 12 months. Following rechallenge (12 months postvaccination) and measurement of antibody responses after 4, 7, and 10 days, rises in SBA titers were only observed in subjects with low (<128) or nonprotective (<8) prerechallenge SBA titers. In subjects with pre rechallenge SBA titers <8, the majority did not reach a protective SBA titer until 7 days post-rechallenge. MenC-specific IgG levels rose in both serum and saliva in correlation with SBA titers. No detectable rise in salivary IgA was observed. Conclusion s.In those individuals who fail to retain protective SBA 12 months after MCC, immunological memory fails to generate protective systemic and mucosal antibodies until 7 days post intranasal challenge with cognate meningococcal polysaccharide. This is likely too slow to protect from natural meningococcal infection. MCC vaccinees rely on persistence of antibody levels rather than immunological memory for sustained protection.

Original languageEnglish
Pages (from-to)1317-1323
Number of pages7
JournalClinical Infectious Diseases
Volume52
Issue number11
DOIs
Publication statusPublished - 1 Jun 2011

Bibliographical note

Funding Information:
Potential conflicts of interest. A. W. H. has received grant support through his institution from Adjuvantix Ltd, Gates Foundation, and the National Institute of Allergy and Infectious Diseases and also holds stock options in Adjuvantix Ltd. R. C. R. has received grant support through his institution from Novartis Vaccines and Diagnostics. All other authors: no conflicts.

Funding Information:
Financial support. This work was supported by the Meningitis Research Foundation (0604.0).

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