4CMenB Immunization Induces Serum Bactericidal Antibodies Against Non-Serogroup B Meningococcal Strains in Adolescents

Alessia Biolchi, Sara Tomei, Brunella Brunelli, Maria Giuliani, Stefania Bambini, Raymond Borrow, Heike Claus, Maria Cecilia O. Gorla, Eva Hong, Ana Paula S. Lemos, Jay Lucidarme, Muhamed Kheir Taha, Ulrich Vogel, Sonia Budroni, Marzia M. Giuliani, Rino Rappuoli, Philip Boucher, Mariagrazia Pizza*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

9 Citations (Scopus)

Abstract

Introduction: Invasive meningococcal disease (IMD) is an important public health concern. In developed countries, most IMD is caused by meningococcal serogroup B (MenB) and two protein-based MenB vaccines are currently available: the four-component vaccine 4CMenB (Bexsero, GSK) and the bivalent vaccine MenB-FHbp (Trumenba, Pfizer). Genes encoding the 4CMenB vaccine antigens are also present in strains belonging to other meningococcal serogroups. Methods: To evaluate the potential of 4CMenB vaccination to protect adolescents against non-MenB IMD, we tested the bactericidal activity of sera from immunized adolescents on 147 (127 European and 20 Brazilian) non-MenB IMD isolates, with a serum bactericidal antibody assay using human complement (hSBA). Serum pools were prepared using samples from randomly selected participants in various clinical trials, pre- and post-vaccination: 12 adolescents who received two doses of 4CMenB 2 months apart, and 10 adolescents who received a single dose of a MenACWY conjugate vaccine (as positive control). Results: 4CMenB pre-immune sera killed 7.5% of the 147 non-MenB isolates at hSBA titers ≥ 1:4. In total, 91 (61.9%) tested isolates were killed by post-dose 2 pooled sera at hSBA titers ≥ 1:4, corresponding to 44/80 (55.0%) MenC, 26/35 (74.3%) MenW, and 21/32 (65.6%) MenY isolates killed. Conclusion: 4CMenB vaccination in adolescents induces bactericidal killing of non-MenB isolates, suggesting that mass vaccination could impact IMD due to serogroups other than MenB.

Original languageEnglish
Pages (from-to)307-316
Number of pages10
JournalInfectious Diseases and Therapy
Volume10
Issue number1
DOIs
Publication statusPublished - Mar 2021

Bibliographical note

Funding Information:
The authors would like to thank Gabriella De Angelis, Maurizio Comanducci and Monica Moschioni for their contributions to this study. Bexsero and Menveo are trademarks owned by or licensed to the GSK group of companies. Trumenba is a trademark of Wyeth LLC (marketed by Pfizer Inc.). This study was sponsored by Novartis Vaccines and Diagnostics, Inc., now part of the GSK group of companies. GlaxoSmithKline Biologicals SA took responsibility for all costs associated with the development and funded the journal?s Rapid Service Fees. The German NRL is supported by the Robert Koch-Institute with funds from the Federal Ministry of Health (funding code 1369?237). Authors thank the Modis platform for editorial assistance and manuscript coordination, on behalf of GSK. Petronela M. Petrar provided medical writing support and Divya Kesters coordinated the manuscript development and provided editorial support. All named authors meet the International Committee of Medical Journal Editors (ICMJE) criteria for authorship for this article, take responsibility for the integrity of the work as a whole, and have given their approval for this version to be published. AB, BB, ST performed the bactericidal assays and contributed to data analysis. SB, MG and MMG contributed to the analysis of the genetic data. MCOG, APSL, HC, UV, MKT, EH, RB and JL provided the isolates, genotyping and phenotyping data and contributed to data discussion. SoB performed the statistical analysis, MMG and RR contributed to the data interpretation and discussion, MP and PB designed the study and wrote the manuscript. This manuscript is based on work that has been previously presented: The 37th Meeting of the European Society for Paediatric Infectious Diseases, Ljubljana, Slovenia, May 6?11, 2019: M. Pizza, A. Biolchi, G. De Angelis, M. Moschioni, S. Tomei, B. Brunelli, M. Giuliani, S. Bambini, R. Borrow, H. Claus, M.C. Outeiro Gorla, E. Hong, A.P. Silva de Lemos, J. Lucidarme, M.K. Taha, U. Vogel, M. Comanducci, S. Budroni, M.M. Giuliani, R. Rappuoli, P. Boucher, 4CMenB, a multicomponent meningococcal vaccine developed for serogroup?B meningococci, elicits cross-reactive immunity against serogroups C, W and Y (Abstract 0255). The 15th Meeting of the European Meningococcal and Haemophilus Disease Society, Lisbon, Portugal, May 27?30 2019: A. Biolchi, G. De Angelis, M. Moschioni, S. Tomei, B. Brunelli, M. Giuliani, S. Bambini, R. Borrow, H. Claus, M.C. Outeiro Gorla, E. Hong, A.P. Silva de Lemos, J. Lucidarme, M.K. Taha, U. Vogel, M. Comanducci, S. Budroni, M.M. Giuliani, R. Rappuoli, P. Boucher, M. Pizza, 4CMenB, a multicomponent meningococcal vaccine developed for serogroup?B meningococci, elicits cross-reactive immunity against serogroups C, W and Y (OC-EMGM2019-13221). The Meningitis Research Foundation Conference 2019, London, UK, November 5?6 2019: M. Pizza, G. De Angelis, M. Moschioni, S. Tomei, B. Brunelli, M. Giuliani, S. Bambini, R. Borrow, H. Claus, M.C. Outeiro Gorla, E. Hong, A.P. Silva de Lemos, J. Lucidarme, M.K. Taha, U. Vogel, M. Comanducci, S. Budroni, M.M. Giuliani, R. Rappuoli, P. Boucher, A. Biolchi, 4CMenB, a multicomponent meningococcal vaccine developed for serogroup?B meningococci, elicits cross-reactive immunity against serogroups C, W and Y (Abstract P12). Alessia Biolchi, Sara Tomei, Brunella Brunelli, Maria Giuliani, Stefania Bambini, Sonia Budroni, Marzia M. Giuliani, Rino Rappuoli and Mariagrazia Pizza are employees of the GSK groups of companies. Sonia Budroni has a patent pending (WO 2015014922 A2). Philip Boucher is an employee of PRA Health Sciences c/o GSK. Muhamed-Kheir Taha received grants from Pfizer and the GSK group of companies and has a patent issued (630133). Jay Lucidarme and Ray Borrow have performed contract research on behalf of Public Health England for the GSK group of companies, Pfizer, and Sanofi Pasteur. Ana Paula S. Lemos reports personal fees from Pfizer and Sanofi-Pasteur. Heike Claus and Ulrich Vogel 's institution received research grants from Novartis. Maria Cecilia O. Gorla and Eva Hong have nothing to disclose. Studies NCT00661713 and NCT00518180 were conducted in accordance with the Declaration of Helsinki. The use of samples was based upon written informed consent obtained from the parents/guardians of the adolescents before the study-specific procedures. However, for a subset of participants in study NCT00661713, the collected informed consent did not include permission for reuse of the biological samples (some of which were used in the current study). Upon discovery of the unintended error, GSK informed the principal investigators, the local ethics committee, and the Ministry of Health of the concerned country and notified all impacted participants. To request access to patient-level data and documents for this study, please submit an enquiry via www.clinicalstudydatarequest.com.

Funding Information:
This study was sponsored by Novartis Vaccines and Diagnostics, Inc., now part of the GSK group of companies. GlaxoSmithKline Biologicals SA took responsibility for all costs associated with the development and funded the journal’s Rapid Service Fees. The German NRL is supported by the Robert Koch-Institute with funds from the Federal Ministry of Health (funding code 1369–237).

Funding Information:
Alessia Biolchi, Sara Tomei, Brunella Brunelli, Maria Giuliani, Stefania Bambini, Sonia Budroni, Marzia M. Giuliani, Rino Rappuoli and Mariagrazia Pizza are employees of the GSK groups of companies. Sonia Budroni has a patent pending (WO 2015014922 A2). Philip Boucher is an employee of PRA Health Sciences c/o GSK. Muhamed-Kheir Taha received grants from Pfizer and the GSK group of companies and has a patent issued (630133). Jay Lucidarme and Ray Borrow have performed contract research on behalf of Public Health England for the GSK group of companies, Pfizer, and Sanofi Pasteur. Ana Paula S. Lemos reports personal fees from Pfizer and Sanofi-Pasteur. Heike Claus and Ulrich Vogel 's institution received research grants from Novartis. Maria Cecilia O. Gorla and Eva Hong have nothing to disclose.

Publisher Copyright:
© 2020, The Author(s).

Copyright:
Copyright 2021 Elsevier B.V., All rights reserved.

Keywords

  • 4CMenB
  • Cross-protection
  • Meningococcal vaccine
  • Non-MenB strains
  • Serum bactericidal antibody activity

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