The impact of pre-existing antibody on subsequent immune responses to meningococcal A-containing vaccines

Olubukola T. Idoko*, Seline N. Okolo, Brian Plikaytis, Adebayo Akinsola, Simonetta Viviani, Raymond Borrow, George Carlone, Helen Findlow, Cheryl Elie, Prasad S. Kulkarni, Marie Pierre Preziosi, Martin Ota, Beate Kampmann

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

14 Citations (Scopus)


Major epidemics of serogroup A meningococcal meningitis continue to affect the African meningitis belt. The development of an affordable conjugate vaccine against the disease became a priority for World Health Organization (WHO) in the late 1990s. Licensing of meningococcal vaccines has been based on serological correlates of protection alone, but such correlates might differ in different geographical regions. If high pre-vaccination antibody concentrations/titers impacts on the response to vaccination and possibly vaccine efficacy, is not clearly understood. We set out to define the pre-vaccination Meningococcal group A (Men A) antibody concentrations/titers in The Gambia and study their impact on the immunogenicity of Men A containing vaccines.Data from subjects originally enrolled in studies to test the safety and immunogenicity of the MenA vaccine recently developed for Africa meningococcal A polysaccharide conjugated to tetanus toxoid, MenAfriVac® (PsA-TT) were analyzed. Participants had been randomized to receive either the study vaccine PsA-TT or the reference quadrivalent plain polysaccharide vaccine containing meningococcal groups A, C, W, and Y, Mencevax® ACWY, GlaxoSmithKline (PsACWY) in a 2:1 ratio. Venous blood samples were collected before and 28 days after vaccination. Antibodies were assayed by enzyme-linked immunosorbent assay (ELISA) for geometric mean concentrations and serum bactericidal antibody (SBA) for functional antibody. The inter age group differences were compared using ANOVA and the pre and post-vaccination differences by t test.Over 80% of the ≥19 year olds had pre-vaccination antibody concentrations above putatively protective concentrations as compared to only 10% of 1-2 year olds. Ninety-five percent of those who received the study vaccine had ≥4-fold antibody responses if they had low pre-vaccination concentrations compared to 76% of those with high pre-vaccination concentrations. All subjects with low pre-vaccination titers attained ≥4-fold responses as compared to 76% with high titers where study vaccine was received.Our data confirm the presence of high pre-vaccination Men A antibody concentrations/titers within the African meningitis belt, with significantly higher concentrations in older individuals. Although all participants had significant increase in antibody levels following vaccination, the four-fold or greater response in antibody titers were significantly higher in individuals with lower pre-existing antibody titers, especially after receiving PsA-TT. This finding may have some implications for vaccination strategies adopted in the future.

Original languageEnglish
Pages (from-to)4220-4227
Number of pages8
Issue number33
Publication statusPublished - 16 Jul 2014

Bibliographical note

Funding Information:
In 1996–1997 a devastating group A meningococcal meningitis epidemic swept throughout the belt, causing over 250,000 cases and 25,000 deaths [8] . This dramatic event and the known limitations of the existing vaccines made it a priority for the World Health Organization (WHO) and ministries of health from African and Eastern Mediterranean countries to advocate for the development of an affordable meningococcal conjugate vaccine [19] . As a result, the Meningitis Vaccine Project (MVP), a partnership between WHO and the Program for Appropriate Technology in Health (PATH), was created in 2001 with funding from the Bill & Melinda Gates Foundation (BMGF) with the goal of developing an affordable group A meningococcal conjugate vaccine for use in the African meningitis belt [20] . A meningococcal A polysaccharide conjugated to tetanus toxoid, MenAfriVac ® vaccine (PsA-TT) was developed by the Serum Institute of India Ltd. (SIIL) and is currently undergoing country-phased introduction across the meningitis belt, already showing a major impact on case reduction and carriage of group A meningococci [10,21–24] .

Copyright 2014 Elsevier B.V., All rights reserved.


  • Antibody
  • Conjugate vaccine
  • Immune response
  • Meningococcal A
  • Pre-existing


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