ArticleInfection and immunity2013
Transcriptional regulation of the nadA gene in Neisseria meningitidis impacts the prediction of coverage of a multicomponent meningococcal serogroup B vaccine.
Article in Infection and immunity, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 60 citations in OpenAlex.
- Structural dynamics and immunogenicity of the recombinant and outer membrane vesicle-embedded Meningococcal antigen NadA.Nature communications · 2026Article
- 4CMenB vaccine coverage of invasive serogroup B meningococci collected in Belgium between 2016 and 2022.Human vaccines & immunotherapeutics · 2025Article
- Methods to evaluate the performance of a multicomponent meningococcal serogroup B vaccine.mSphere · 2025Review
- Genetic characterization and estimated 4CMenB vaccine strain coverage of 284Human vaccines & immunotherapeutics · 2024Article
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- Characterisation and Immunogenicity ofFrontiers in immunology · 2024Article
- Microevolution and Its Impact on Hypervirulence, Antimicrobial Resistance, and Vaccine Escape inMicroorganisms · 2023Review
- Immunogenicity of trimeric autotransporter adhesins and their potential as vaccine targets.Medical microbiology and immunology · 2020Review
- Single Domain Antibodies Targeting Receptor Binding Pockets of NadA Restrain Adhesion ofFrontiers in molecular biosciences · 2020Article
- [From a pathogen's genome to an effective vaccine: the four-component meningococcal serogroup B vaccine].Revista espanola de quimioterapia : publicacion oficial de la Sociedad Espanola de Quimioterapia · 2019Review
- The Development of a Vaccine Against Meningococcus B Using Reverse Vaccinology.Frontiers in immunology · 2019Review
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- Phase Variation of NadA in Invasive Neisseria meningitidis Isolates Impacts on Coverage Estimates for 4C-MenB, a MenB Vaccine.Journal of clinical microbiology · 2018Article
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- Genomic Surveillance of 4CMenB Vaccine Antigenic Variants among Disease-Causing Neisseria meningitidis Isolates, United Kingdom, 2010-2016.Emerging infectious diseases · 2018Article
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- Discordant Effects of Licensed Meningococcal Serogroup B Vaccination on Invasive Disease and Nasal Colonization in a Humanized Mouse Model.The Journal of infectious diseases · 2017Article
- Serum Bactericidal Antibody Responses of Adults Immunized with the MenB-4C Vaccine against Genetically Diverse Serogroup B Meningococci.Clinical and vaccine immunology : CVI · 2017Article
- Molecular Basis of Ligand-Dependent Regulation of NadR, the Transcriptional Repressor of Meningococcal Virulence Factor NadA.PLoS pathogens · 2016Article
Corrections and comments
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Authors and funding
14 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The NadA adhesin is a major component of 4CMenB, a novel vaccine to prevent meningococcus serogroup B (MenB) infection. Under in vitro growth conditions, nadA is repressed by the regulator NadR and poorly expressed, resulting in inefficient killing of MenB strains by anti-NadA antibodies. Interestingly, sera from children infected with strains that express low levels of NadA in laboratory growth nevertheless recognize the NadA antigen, suggesting that NadA expression during infection may be different from that observed in vitro. In a strain panel covering a range of NadA levels, repression was relieved through deleting nadR. All nadR knockout strains expressed high levels of NadA and were efficiently killed by sera from subjects immunized with 4CMenB. A selected MenB strain, NGP165, mismatched for other vaccine antigens, is not killed by sera from immunized infants when the strain is grown in vitro. However, in an in vivo passive protection model, the same sera effectively protected infant rats from bacteremia with NGP165. Furthermore, we identify a novel hydroxyphenylacetic acid (HPA) derivative, reported by others to be produced during inflammation, which induces expression of NadA in vitro, leading to efficient antibody-mediated killing. Finally, using bioluminescent reporters, nadA expression in the infant rat model was induced in vivo at 3 h postinfection. Our results suggest that during infectious disease, NadR repression is alleviated due to niche-specific signals, resulting in high levels of NadA expression from any nadA-positive (nadA(+)) strain and therefore efficient killing by anti-NadA antibodies elicited by the 4CMenB vaccine.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.