{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T19:49:03Z","timestamp":1792784943443,"version":"4.5.0"},"reference-count":28,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2021,2,23]],"date-time":"2021-02-23T00:00:00Z","timestamp":1614038400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,2,23]],"date-time":"2021-02-23T00:00:00Z","timestamp":1614038400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"This work was sponsored by GlaxoSmithKline Biologicals SA, which funded all costs associated with the development and the publishing of the present manuscript."}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["npj Vaccines"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Immunogenicity of vaccines against meningococcal serogroup B (MenB) has been assessed pre-licensure with a human serum bactericidal activity assay (hSBA), tested against small numbers of strains. We report the qualification\/validation of an alternative qualitative hSBA which uses endogenous complement (enc-hSBA) present in the vaccinee\u2019s serum. Serum samples were collected from adults pre-vaccination and post-vaccination with the 4-component MenB vaccine (4CMenB). A representative panel of invasive isolates and 4 antigen-specific indicator strains were used in qualification experiments. Each strain was tested in \u22653 experiments with pre\/post-vaccination sera to evaluate intermediate precision. A 110-strain panel and the 4 indicator strains met qualification criteria, demonstrating assay precision. Assay robustness, specificity and sensitivity were demonstrated using the 4 indicator strains. Enc-hSBA is highly standardized, allows testing across large panels of epidemiologically-relevant MenB strains, and accounts for complement activity differences between vaccinees. Therefore, enc-hSBA enables a more accurate estimation of effectiveness for vaccines against MenB.<\/jats:p>","DOI":"10.1038\/s41541-021-00286-8","type":"journal-article","created":{"date-parts":[[2021,2,23]],"date-time":"2021-02-23T06:05:33Z","timestamp":1614060333000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Endogenous complement human serum bactericidal assay (enc-hSBA) for vaccine effectiveness assessments against meningococcal serogroup B"],"prefix":"10.1038","volume":"6","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4489-7863","authenticated-orcid":false,"given":"Annett","family":"Kleinschmidt","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kumaran","family":"Vadivelu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Serino","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nina","family":"Neidig","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bertrand","family":"de Wergifosse","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,2,23]]},"reference":[{"key":"286_CR1","doi-asserted-by":"publisher","first-page":"2768","DOI":"10.1016\/j.vaccine.2019.04.020","volume":"37","author":"B Wang","year":"2019","unstructured":"Wang, B., Santoreneos, R., Giles, L., Haji Ali Afzali, H. & Marshall, H. Case fatality rates of invasive meningococcal disease by serogroup and age: a systematic review and meta-analysis. Vaccine 37, 2768\u20132782 (2019).","journal-title":"Vaccine"},{"key":"286_CR2","first-page":"521","volume":"86","author":"Meningococcal vaccines.","year":"2011","unstructured":"Meningococcal vaccines. WHO position paper, November 2011. Wkly Epidemiol. Rec. 86, 521\u2013539 (2011).","journal-title":"Wkly Epidemiol. Rec."},{"key":"286_CR3","doi-asserted-by":"publisher","first-page":"S3","DOI":"10.1016\/j.jadohealth.2016.04.012","volume":"59","author":"SI Pelton","year":"2016","unstructured":"Pelton, S. I. The global evolution of meningococcal epidemiology following the introduction of meningococcal vaccines. J. Adolesc. Health 59, S3\u2013S11 (2016).","journal-title":"J. Adolesc. Health"},{"key":"286_CR4","doi-asserted-by":"publisher","first-page":"421","DOI":"10.1007\/s40121-018-0213-2","volume":"7","author":"KJ Olbrich","year":"2018","unstructured":"Olbrich, K. J. et al. Systematic review of invasive meningococcal disease: sequelae and quality of life impact on patients and their caregivers. Infect. Dis. Ther. 7, 421\u2013438 (2018).","journal-title":"Infect. Dis. Ther."},{"key":"286_CR5","doi-asserted-by":"publisher","first-page":"103571","DOI":"10.1016\/j.micpath.2019.103571","volume":"134","author":"A Purmohamad","year":"2019","unstructured":"Purmohamad, A. et al. Global estimate of Neisseria meningitidis serogroups proportion in invasive meningococcal disease: A systematic review and meta-analysis. Micro. Pathog. 134, 103571 (2019).","journal-title":"Micro. Pathog."},{"key":"286_CR6","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1080\/14760584.2019.1557520","volume":"18","author":"R Acevedo","year":"2019","unstructured":"Acevedo, R. et al. The Global Meningococcal Initiative meeting on prevention of meningococcal disease worldwide: Epidemiology, surveillance, hypervirulent strains, antibiotic resistance and high-risk populations. Expert Rev. Vaccines 18, 15\u201330 (2019).","journal-title":"Expert Rev. Vaccines"},{"key":"286_CR7","unstructured":"World Health Organization. Invasive meningococcal disease\u2013Serogroup distribution. http:\/\/www.who.int\/emergencies\/diseases\/meningitis\/serogroup-distribution-2018.pdf?ua=1 (2018)."},{"key":"286_CR8","doi-asserted-by":"publisher","first-page":"355","DOI":"10.1016\/S0140-6736(83)90340-9","volume":"2","author":"J Finne","year":"1983","unstructured":"Finne, J., Leinonen, M. & Makela, P. H. Antigenic similarities between brain components and bacteria causing meningitis. Implications for vaccine development and pathogenesis. Lancet 2, 355\u2013357 (1983).","journal-title":"Lancet"},{"key":"286_CR9","doi-asserted-by":"publisher","first-page":"433","DOI":"10.1080\/14760584.2017.1308828","volume":"16","author":"D Toneatto","year":"2017","unstructured":"Toneatto, D., Pizza, M., Masignani, V. & Rappuoli, R. Emerging experience with meningococcal serogroup B protein vaccines. Expert Rev. Vaccines 16, 433\u2013451 (2017).","journal-title":"Expert Rev. Vaccines"},{"key":"286_CR10","doi-asserted-by":"publisher","first-page":"1111","DOI":"10.1080\/14760584.2018.1547637","volume":"17","author":"R Rappuoli","year":"2018","unstructured":"Rappuoli, R., Pizza, M., Masignani, V. & Vadivelu, K. Meningococcal B vaccine (4CMenB): the journey from research to real world experience. Expert Rev. Vaccines 17, 1111\u20131121 (2018).","journal-title":"Expert Rev. Vaccines"},{"key":"286_CR11","doi-asserted-by":"publisher","first-page":"225","DOI":"10.1080\/14760584.2019.1578217","volume":"18","author":"J Findlow","year":"2019","unstructured":"Findlow, J., Nuttens, C. & Kriz, P. Introduction of a second MenB vaccine into Europe-needs and opportunities for public health. Expert Rev. Vaccines 18, 225\u2013239 (2019).","journal-title":"Expert Rev. Vaccines"},{"key":"286_CR12","unstructured":"European Medicines Agency. Bexsero. Summary of product characteristics. http:\/\/www.ema.europa.eu\/en\/documents\/product-information\/bexsero-epar-product-information_en.pdf (2020)."},{"key":"286_CR13","unstructured":"European Medicines Agency. Trumenba. Summary of product characteristics. http:\/\/www.ema.europa.eu\/en\/documents\/product-information\/trumenba-epar-product-information_en.pdf (2020)."},{"key":"286_CR14","doi-asserted-by":"publisher","first-page":"1307","DOI":"10.1084\/jem.129.6.1307","volume":"129","author":"I Goldschneider","year":"1969","unstructured":"Goldschneider, I., Gotschlich, E. C. & Artenstein, M. S. Human immunity to the meningococcus. I. The role of humoral antibodies. J. Exp. Med. 129, 1307\u20131326 (1969).","journal-title":"J. Exp. Med."},{"key":"286_CR15","doi-asserted-by":"crossref","unstructured":"Brehony, C., Hill, D. M., Lucidarme, J., Borrow, R. & Maiden, M. C. Meningococcal vaccine antigen diversity in global databases. Euro. Surveill. 20, 30084 (2015).","DOI":"10.2807\/1560-7917.ES.2015.20.49.30084"},{"key":"286_CR16","doi-asserted-by":"publisher","first-page":"405","DOI":"10.1146\/annurev-genet-120213-092007","volume":"48","author":"E Rotman","year":"2014","unstructured":"Rotman, E. & Seifert, H. S. The genetics of Neisseria species. Annu. Rev. Genet. 48, 405\u2013431 (2014).","journal-title":"Annu. Rev. Genet."},{"key":"286_CR17","doi-asserted-by":"crossref","unstructured":"Rajam, G. et al. Meningococcal Antigen Typing System (MATS)-based Neisseria meningitidis serogroup B coverage prediction for the MenB-4C vaccine in the United States. mSphere 2, e00261-17 (2017).","DOI":"10.1128\/mSphere.00261-17"},{"key":"286_CR18","doi-asserted-by":"publisher","first-page":"4739","DOI":"10.1016\/j.vaccine.2011.04.092","volume":"29","author":"X Wang","year":"2011","unstructured":"Wang, X. et al. Prevalence and genetic diversity of candidate vaccine antigens among invasive Neisseria meningitidis isolates in the United States. Vaccine 29, 4739\u20134744 (2011).","journal-title":"Vaccine"},{"key":"286_CR19","doi-asserted-by":"publisher","first-page":"991","DOI":"10.1016\/j.vaccine.2018.12.061","volume":"37","author":"A Muzzi","year":"2019","unstructured":"Muzzi, A. et al. Genetic meningococcal antigen typing system (gMATS): A genotyping tool that predicts 4CMenB strain coverage worldwide. Vaccine 37, 991\u20131000 (2019).","journal-title":"Vaccine"},{"key":"286_CR20","doi-asserted-by":"publisher","first-page":"426","DOI":"10.1016\/j.jinf.2019.09.001","volume":"79","author":"HY Chang","year":"2019","unstructured":"Chang, H. Y. et al. Distribution of Neisseria meningitidis serogroup b (NmB) vaccine antigens in meningococcal disease causing isolates in the United States during 2009-2014, prior to NmB vaccine licensure. J. Infect. 79, 426\u2013434 (2019).","journal-title":"J. Infect."},{"key":"286_CR21","doi-asserted-by":"publisher","first-page":"5309","DOI":"10.1016\/j.vaccine.2018.07.016","volume":"36","author":"JA Welsch","year":"2018","unstructured":"Welsch, J. A. et al. Breadth of coverage against a panel of 110 invasive disease isolates, immunogenicity and safety for 2 and 3 doses of an investigational MenABCWY vaccine in US adolescents-Results from a randomized, controlled, observer-blind phase II study. Vaccine 36, 5309\u20135317 (2018).","journal-title":"Vaccine"},{"key":"286_CR22","doi-asserted-by":"publisher","first-page":"e00036","DOI":"10.1128\/mBio.00036-18","volume":"9","author":"LK McNeil","year":"2018","unstructured":"McNeil, L. K. et al. Predicting the susceptibility of meningococcal serogroup B isolates to bactericidal antibodies elicited by bivalent rLP2086, a novel prophylactic vaccine. mBio 9, e00036\u201300018 (2018).","journal-title":"mBio"},{"key":"286_CR23","doi-asserted-by":"crossref","unstructured":"Frosi, G. et al. Bactericidal antibody against a representative epidemiological meningococcal serogroup B panel confirms that MATS underestimates 4CMenB vaccine strain coverage. Vaccine 31, 4968\u20134974 (2013).","DOI":"10.1016\/j.vaccine.2013.08.006"},{"key":"286_CR24","doi-asserted-by":"publisher","first-page":"945","DOI":"10.1080\/21645515.2019.1688039","volume":"16","author":"M Stella","year":"2020","unstructured":"Stella, M. et al. Does vaccination with 4CMenB convey protection against meningococcal serogroup B strains not predicted to be covered by MATS? A study of the UK clonal complex cc269. Hum. Vaccin. Immunother. 16, 945\u2013948 (2020).","journal-title":"Hum. Vaccin. Immunother."},{"key":"286_CR25","doi-asserted-by":"publisher","first-page":"309","DOI":"10.1056\/NEJMoa1901229","volume":"382","author":"SN Ladhani","year":"2020","unstructured":"Ladhani, S. N. et al. Vaccination of infants with meningococcal group B vaccine (4CMenB) in England. N. Engl. J. Med. 382, 309\u2013317 (2020).","journal-title":"N. Engl. J. Med."},{"key":"286_CR26","doi-asserted-by":"publisher","first-page":"4243","DOI":"10.1016\/j.vaccine.2019.06.021","volume":"37","author":"G Deceuninck","year":"2019","unstructured":"Deceuninck, G. et al. Impact of a mass vaccination campaign against Serogroup B meningococcal disease in the Saguenay-Lac-Saint-Jean region of Quebec four years after its launch. Vaccine 37, 4243\u20134245 (2019).","journal-title":"Vaccine"},{"key":"286_CR27","doi-asserted-by":"publisher","first-page":"2491","DOI":"10.1080\/21645515.2019.1593082","volume":"15","author":"J Findlow","year":"2019","unstructured":"Findlow, J. & Balmer, P. & Borrow, R. A review of complement sources used in serum bactericidal assays for evaluating immune responses to meningococcal ACWY conjugate vaccines. Hum. Vaccin Immunother. 15, 2491\u20132500 (2019).","journal-title":"Hum. Vaccin Immunother."},{"key":"286_CR28","doi-asserted-by":"publisher","first-page":"63","DOI":"10.1016\/j.pharmthera.2016.11.014","volume":"172","author":"SR Barnum","year":"2017","unstructured":"Barnum, S. R. Complement: a primer for the coming therapeutic revolution. Pharm. Ther. 172, 63\u201372 (2017).","journal-title":"Pharm. Ther."}],"container-title":["npj Vaccines"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41541-021-00286-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41541-021-00286-8","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41541-021-00286-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,2]],"date-time":"2022-12-02T18:29:34Z","timestamp":1670005774000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41541-021-00286-8"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,2,23]]},"references-count":28,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2021,12]]}},"alternative-id":["286"],"URL":"https:\/\/doi.org\/10.1038\/s41541-021-00286-8","relation":{},"ISSN":["2059-0105"],"issn-type":[{"value":"2059-0105","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,2,23]]},"assertion":[{"value":"24 July 2020","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"14 January 2021","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"23 February 2021","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"All authors are employees of the GSK group of companies. A.K., K.V., and L.S. hold shares in the GSK group of companies as part of their employee remuneration. All authors declare no non-financial competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"29"}}