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Updated: Jan 20, 2026
Assessment of Opsonophagocytic Killing Activity against Bacterial Pathogens
Multi-component meningococcal serogroup B (MenB)-4C vaccine induces effective opsonophagocytic killing in children
B van den Broek1,2,3,4, C A C M van Els5, B Kuipers5
1Pediatric Infectious Diseases and Immunology, Amalia Children's Hospital, Nijmegen, the Netherlands.
Insights
Meningococcal serogroup B (MenB) vaccination is recommended for children with complement deficiencies. This study shows MenB-4C vaccination effectively induces protective antibodies and complement-dependent killing, supporting its use in these vulnerable patients.
Area of Science:
- Immunology
- Vaccinology
- Complement System Biology
Background:
- Meningococcal serogroup B (MenB) vaccination is recommended for individuals with complement deficiencies.
- While immunogenicity of MenB vaccines is established in this group, clinical efficacy remains unproven.
- Complement deficiencies affect the body's ability to fight infections, including those caused by Neisseria meningitidis.
Purpose of the Study:
- To assess the immunogenicity and functional efficacy of the multi-component meningococcal serogroup B (MenB)-4C vaccine in children with complement deficiencies.
- To evaluate vaccine-induced antibody responses and complement-mediated bactericidal activity.
- To determine if MenB-4C vaccination can induce effective opsonophagocytic killing in children with alternative pathway or late terminal pathway deficiencies.
Main Methods:
- Serum samples were collected from children with alternative pathway or late terminal pathway complement deficiencies before and after MenB-4C vaccination.
- Vaccine immunogenicity was assessed using whole cell enzyme-linked immunosorbent assay (ELISA) against Neisseria meningitidis serogroup B strains.
- Vaccine-mediated protection was evaluated through serum bactericidal activity assays (using exogenous and autologous serum) and complement-dependent opsonophagocytic killing assays.
Main Results:
- MenB-4C vaccination induced significant antibody titers against Neisseria meningitidis serogroup B in all vaccinated children.
- Classical serum bactericidal activity assays with exogenous serum demonstrated vaccine-induced antibodies capable of activating complement.
- However, children with late terminal pathway deficiency showed no complement-mediated lysis with autologous serum.
- Despite this, MenB-4C vaccination induced effective complement-dependent opsonophagocytic killing in reconstituted whole blood, even in children with complement deficiencies.
Conclusions:
- Meningococcal serogroup B (MenB)-4C vaccination is immunogenic and induces functional antibody responses in children with complement deficiencies.
- The vaccine promotes complement-dependent opsonophagocytic killing, crucial for pathogen clearance, even in the presence of complement pathway defects.
- These findings provide strong support for the recommendation of MenB-4C vaccination in all complement-deficient children to enhance protection against meningococcal disease.
Abstract:
Vaccination against meningococcal serogroup B is recommended for patients with a complement deficiency; however, although immunogenicity in this patient group has been shown, efficacy has not yet been established. In this study, we collected serum from children with a complement deficiency in the alternative pathway or in late terminal pathway before and after vaccination with multi-component meningococcal serogroup B (MenB)-4C. MenB-4C is a multi-component, protein-based vaccine against MenB consisting of factor H-binding protein, Neisserial heparin-binding protein, Neisserial adhesion A and outer membrane vesicles containing Porin A. We assessed the vaccine immunogenicity and vaccine-mediated protection by a whole cell enzyme-linked immunosorbent assay with Neisseria meningitidis serogroup B strains H44/76, 5/99 and NZ98/254, which shows that vaccination induced antibody titers against meningococcus. We show that the classical serum bactericidal activity assay with exogenous serum indicates the presence of vaccine-induced antibodies and capacity to activate complement-mediated pathogen lysis. However, in children with a late terminal pathway deficiency, no complement-mediated pathogen lysis was observed when autologous serum was applied in the serum bactericidal activity assay, demonstrating a lack of serum bactericidal activity in children with complement deficiencies. However, MenB-4C vaccination still induced effective complement-dependent opsonophagocytic killing against N. meningitidis serogroup B in reconstituted whole blood with autologous serum from children with an alternative pathway or late terminal pathway deficiency. These findings support the recommendation to vaccinate all complement-deficient children against MenB.
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