Federico Martinón-Torres1, Ewa Bernatowska2, Anna Shcherbina3, Susanna Esposito4, Leszek Szenborn5, Magda Campins Marti6, Stephen Hughes7, Saul N Faust8, Luis I Gonzalez-Granado9, Ly-Mee Yu10, Diego D'Agostino11, Marco Calabresi12, Daniela Toneatto12, Matthew D Snape13,14. 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.
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-deficientparticipants 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-deficientparticipant. 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-deficientchildren (especially those with terminal chain complement deficiency or those on eculizumab therapy) must be determined by ongoing surveillance for vaccine failures.
Authors: Sarah A Mbaeyi; Catherine H Bozio; Jonathan Duffy; Lorry G Rubin; Susan Hariri; David S Stephens; Jessica R MacNeil Journal: MMWR Recomm Rep Date: 2020-09-25
Authors: Raquel Medeiros de Souza; Bernardo Henrique Mendes Correa; Paulo Henrique Moreira Melo; Pedro Antunes Pousa; Tamires Sara Campos de Mendonça; Lucas Gustavo Castelar Rodrigues; Ana Cristina Simões E Silva Journal: Pediatr Nephrol Date: 2022-07-21 Impact factor: 3.651