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Pediatrics. 2018 Sep;142(3). pii: e20174250. doi: 10.1542/peds.2017-4250. Epub 2018 Aug 1.

Meningococcal B Vaccine Immunogenicity in Children With Defects in Complement and Splenic Function.

Author information

1
Translational Pediatrics and Infectious Diseases, Hospital Clinico Universitario de Santiago de Compostela, Santiago de Compostela, Spain.
2
Department of Immunology, The Children's Memorial Health Institute, Warsaw, Poland.
3
Research and Clinical Centre of Pediatric Hematology, Oncology and Immunology named after Dmitry Rogachev, Moscow, Russian Federation.
4
Pediatric Clinic, Department of Surgical and Biomedical Sciences, Università degli Studi di Perugia, Perugia, Italy.
5
Department of Pediatric Infectious Diseases, Wroclaw Medical University, Wroclaw, Poland.
6
Hospital Universitario Vall d'Hebron, Barcelona, Spain.
7
Royal Manchester Children's Hospital, Manchester, United Kingdom.
8
National Institute for Health Research Wellcome Trust Clinical Research Facility, University of Southampton and University Hospital Southampton NHS Foundation Trust, Southampton, United Kingdom.
9
Immunodeficiencies Unit, Department of Pediatrics, University Hospital 12 de Octubre, Research Institute Hospital 12 Octubre (i+12) and Associate Professor of Pediatrics, Complutense University of Madrid, Madrid, Spain.
10
Nuffield Department of Primary Care Health Sciences and.
11
GlaxoSmithKline, Amsterdam, The Netherlands.
12
GlaxoSmithKline, Siena, Italy; and.
13
Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, United Kingdom; matthew.snape@paediatrics.ox.ac.uk.
14
National Institute for Health Research Oxford Biomedical Research Centre, Oxford, United Kingdom.

Abstract

BACKGROUND:

The capsular group B meningococcal vaccine (4CMenB) is recommended for children with complement deficiencies, asplenia, and splenic dysfunction; however, data on the immunogenicity of 4CMenB in these "at-risk" children are missing.

METHODS:

Participants aged 2 to 17 years in Italy, Spain, Poland, the United Kingdom, and Russia with complement deficiencies, asplenia, or splenic dysfunction received 2 doses of 4CMenB 2 months apart, as did healthy children in the control group. Exogenous and endogenous human complement serum bactericidal activity (SBA) was determined at baseline and 1 month after the second immunization against 4 test strains: H44/76 (assessing vaccine antigen factor H binding protein), 5/99 (Neisserial adhesion A), NZ98/254 (Porin A), and M10713 (Neisserial heparin binding antigen).

RESULTS:

Of 239 participants (mean age 10.3 years, 45% female), 40 children were complement deficient (9 eculizumab therapy, 4 terminal-chain deficiencies, 27 "other"), 112 children had asplenia or splenic dysfunction (8 congenital asplenia, 8 functional asplenia, 96 splenectomy), and 87 children were in the control group. After immunization, the proportions of complement-deficient participants with exogenous complement SBA titers ≥1:5 were 87% (H44/76), 95% (5/99), 68% (NZ98/254), and 73% (M10713), compared with 97%, 100%, 86%, and 94%, respectively, for asplenic children and 98%, 99%, 83%, and 99% for children in the control group. When testing with endogenous complement, strain-specific bactericidal activity was evident in only 1 eculizumab-treated participant and 1 terminal chain complement-deficient participant.

CONCLUSIONS:

4CMenB administration is similarly immunogenic in healthy children and those with asplenia or splenic dysfunction. The significance of the trend to lower responses of SBA titers in complement-deficient children (especially those with terminal chain complement deficiency or those on eculizumab therapy) must be determined by ongoing surveillance for vaccine failures.

TRIAL REGISTRATION:

ClinicalTrials.gov NCT02141516.

PMID:
30068713
DOI:
10.1542/peds.2017-4250
[Indexed for MEDLINE]
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Conflict of interest statement

POTENTIAL CONFLICT OF INTEREST: The institution of Dr Martinón-Torres received clinical trial fees from Novartis during the conduct of this study, and he received personal fees and/or nonfinancial support and/or grants and/or other from Novartis, Pfizer, Sanofi-Pasteur MSD (SPMSD), the GlaxoSmithKline (GSK) group of companies, and/or Merck outside the submitted work. Prof Esposito reports grants from Novartis, the GSK group of companies, Pfizer, Sanofi-Pasteur, and Valeas, and personal fees from Novartis, the GSK group of companies, Pfizer, Sanofi-Pasteur, Novavax, and Vifor outside the submitted work. Prof Szenborn received personal fees from Novartis and the GSK group of companies during the conduct of the study. The institution of Prof Marti received clinical trial fees from Novartis during the conduct of the study, and she received grants from Novartis, GSK, and Pfizer outside of the submitted work. The institution of Prof Faust received grants from GSK group of companies during the conduct of the study and received grants for his participation in advisory boards (Astra Zeneca and Cubist) and speaking engagements (Pfizer). Prof Faust acts as an investigator for clinical studies from both noncommercial funding bodies and commercial sponsors (ie, some or all of Novartis Vaccines, the GSK group of companies, MedImmune and/or AstraZeneca, and Pfizer Vaccines) conducted on behalf of Southampton University Hospital NHS Foundation Trust and the University of Southampton. The institution of Prof Gonzalez-Granado received clinical trial fees from Novartis during the conduct of the study and he has received grants for his participation in advisory boards and speaking engagements (CSL Behring and Baxter). Dr Calabresi and Mr D’Agostino were employees and Dr Toneatto is an employee of the GSK group of companies. Dr Toneatto owns stock and/or stock options in the GSK group of companies. Dr Snape acts as an investigator for clinical studies from both noncommercial funding bodies and commercial sponsors (ie, some or all of Novartis Vaccines, the GSK group of companies, Sanofi-Aventis, SPMSD, MedImmune, and Pfizer Vaccines) conducted on behalf of the University of Oxford and Oxford University Hospitals NHS trust. The NIHR Oxford Biomedical Research Centre provides salary support for Dr Snape, who is a Jenner Investigator; the other authors have indicated they have no potential conflicts of interest to disclose.

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