Immunogenicity profiling of protein antigens from capsular group B Neisseria meningitidis

Awanye, Amaka M.; Chang, Chun-Mien; Wheeler, Jun X.; Chan, Hannah; Marsay, Leanne; Dold, Christina; Rollier, Christine S.; Bird, Louise E.; Nettleship, Joanne E.; Owens, Raymond J.; Pollard, Andrew J.; Derrick, Jeremy P.

doi:10.1038/s41598-019-43139-0

Cited by 19 publications

(19 citation statements)

References 90 publications

(106 reference statements)

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“…Among them, OMV minor antigens are known to play a synergistic role in the cross-bactericidal activity. In a recent study, sera from adults vaccinated with an OMV vaccine were used to screen an antigen microarray containing 91 outer membrane proteins 27 . The authors identified six very high responding antigens corresponding to OMVs components that could play a role in the protective immune response induced by OMV based vaccines.…”

Section: Resultsmentioning

confidence: 99%

“…Nowadays, a faster and more powerful technology to perform epitope mapping is represented by protein microarrays, which allow analysing simultaneously short and long peptides that are representative of all immunogenic regions of an antigen, including both linear and conformational epitopes, with the further advantage of using only minimal volumes of biological samples. Proteomic microarrays generated by spotting full-length antigens are largely used to profile responses to bacterial infections 25 , 26 or following vaccination 27 – 29 or as diagnostic tool 30 .…”

Section: Introductionmentioning

confidence: 99%

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Immunological fingerprint of 4CMenB recombinant antigens via protein microarray reveals key immunosignatures correlating with bactericidal activity

Bartolini¹,

Borgogni²,

Bruttini

et al. 2020

Nat Commun

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Serogroup B meningococcus (MenB) is a leading cause of meningitis and sepsis across the world and vaccination is the most effective way to protect against this disease. 4CMenB is a multi-component vaccine against MenB, which is now licensed for use in subjects >2 months of age in several countries. In this study, we describe the development and use of an ad hoc protein microarray to study the immune response induced by the three major 4CMenB antigenic components (fHbp, NHBA and NadA) in individual sera from vaccinated infants, adolescents and adults. The resulting 4CMenB protein antigen fingerprinting allowed the identification of specific human antibody repertoire correlating with the bactericidal response elicited in each subject. This work represents an example of epitope mapping of the immune response induced by a multicomponent vaccine in different age groups with the identification of protective signatures. It shows the high flexibility of this microarray based methodology in terms of high-throughput information and minimal volume of biological samples needed.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Immunological fingerprint of 4CMenB recombinant antigens via protein microarray reveals key immunosignatures correlating with bactericidal activity

Bartolini¹,

Borgogni²,

Bruttini

et al. 2020

Nat Commun

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“…Even among immunised children with culture-confirmed IMD, we have a poor understanding of which vaccine antigens are important for protection, whether some of the vaccine antigens offer more protection than others or whether some combinations of vaccine antigens might be more protective than others through synergy, for example. At the same time, in addition to harbouring the immunodominant PorA 1.4 antigen, the OMV component of 4CMenB has multiple minor antigens which also help protect against IMD, but their contribution is difficult to measure 51. There are currently no data to suggest that breakthrough MenB cases in immunised children are associated with an underlying immune deficiency or an increased risk of recurrent infections.…”

Section: Discussionmentioning

confidence: 99%

Success of 4CMenB in preventing meningococcal disease: evidence from real-world experience

et al. 2020

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Meningococcal disease remains one of the most feared infectious diseases worldwide because of its sudden onset, rapid progression and high case fatality rates, while survivors are often left with severe long-term sequelae. Young children have the highest incidence of invasive meningococcal disease (IMD), and nearly all cases in the UK, as in most of Europe and many other industrialised countries, are due to group B meningococci (MenB). The licensure of a broad-coverage, recombinant protein-based MenB vaccine (4CMenB) in 2013 was, therefore, heralded a major breakthrough in the fight against IMD. This vaccine was, however, licensed on immunogenicity and reactogenicity studies only, raising uncertainties about field effectiveness, long-term safety and antibody persistence. In 2015, the UK became the first country to implement 4CMenB into the national infant immunisation schedule and, since then, several countries have followed suit. Seven years after licensure, a wealth of real-world data has emerged to confirm 4CMenB effectiveness, along with large-scale safety data, duration of protection in different age groups, successful strategies to reduce vaccine reactogenicity, impact on carriage in adolescents and the potential for 4CMenB to protect against other meningococcal serogroups and against gonorrhoea. A number of questions, however, remain unanswered, including the investigation and management of vaccine-associated fever in infants, as well as disease severity and assessment of breakthrough cases in immunised children. Increasing use of 4CMenB will provide answers in due course. We now have vaccines against all the major serogroups causing IMD worldwide. Next-generation and combination vaccines against multiple serogroups look very promising.

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“…Lipoproteins play a role in bacterial membrane metabolism and functions, in pathogenesis by mediating host cell adhesion and inflammatory responses and are considered good vaccine candidates [95]. Examples in Neisseriae include established vaccine targets (factor H binding protein (fHbp) part of both Bexsero and Trumenba [92,96]) and preclinical targets (reviewed in Reference [97]), for example TbpB [25], NMB0928 [70,73] (homolog of NGO0948), MetQ [30,34]. Two candidates were potentially involved in metal binding, NGO1215 (AccA [86]), and NGO1701 (hypothetical).…”

Section: Discussionmentioning

confidence: 99%

“…(2) NGO0690, a putative P/OM lipoprotein, possibly involved in threonine biosynthesis and pilin antigenicity [67]; (3) NGO0948, a P/OM lipoprotein member of the NlpB/DapX family (COG3317), homolog to BamC (a member of the BAM complex [68], surface-exposed in E. coli [69]) and a potential meningococcal vaccine antigen (NMB0928 [70][71][72][73]); (4) NGO1043, a hypothetical P/OM putative lipoprotein, possibly glycosylated and a substrate for phosphoethanolamine (PE) addition [74,75], with homology to the meningococcal antigen Ag473 [76]; (5) NGO1215, a hypothetical P protein with homology to a copper chaperone PCu(A)C superfamily (COG2847) (potential virulence factors) [77] and reported as AccA [78], and (6) NGO1701, a P membrane protein with homology to a TAT_Cys_rich four helix bundle copper-binding protein of the DUF326 superfamily. Table 1 summarizes the major CASS features for these candidates.…”

Section: Discovery and Analysis Phase (Dap)mentioning

confidence: 99%

Integrated Bioinformatic Analyses and Immune Characterization of New Neisseria gonorrhoeae Vaccine Antigens Expressed during Natural Mucosal Infection

et al. 2019

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There is an increasingly severe trend of antibiotic-resistant Neisseria gonorrhoeae strains worldwide and new therapeutic strategies are needed against this sexually-transmitted pathogen. Despite the urgency, progress towards a gonococcal vaccine has been slowed by a scarcity of suitable antigens, lack of correlates of protection in humans and limited animal models of infection. N. gonorrhoeae gene expression levels in the natural human host does not reflect expression in vitro, further complicating in vitro-basedvaccine analysis platforms. We designed a novel candidate antigen selection strategy (CASS), based on a reverse vaccinology-like approach coupled with bioinformatics. We utilized the CASS to mine gonococcal proteins expressed during human mucosal infection, reported in our previous studies, and focused on a large pool of hypothetical proteins as an untapped source of potential new antigens. Via two discovery and analysis phases (DAP), we identified 36 targets predicted to be immunogenic, membrane-associated proteins conserved in N. gonorrhoeae and suitable for recombinant expression. Six initial candidates were produced and used to immunize mice. Characterization of the immune responses indicated cross-reactive antibodies and serum bactericidal activity against different N. gonorrhoeae strains. These results support the CASS as a tool for the discovery of new vaccine candidates.

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Immunogenicity profiling of protein antigens from capsular group B Neisseria meningitidis

Cited by 19 publications

References 90 publications

Immunological fingerprint of 4CMenB recombinant antigens via protein microarray reveals key immunosignatures correlating with bactericidal activity

Immunological fingerprint of 4CMenB recombinant antigens via protein microarray reveals key immunosignatures correlating with bactericidal activity

Success of 4CMenB in preventing meningococcal disease: evidence from real-world experience

Integrated Bioinformatic Analyses and Immune Characterization of New Neisseria gonorrhoeae Vaccine Antigens Expressed during Natural Mucosal Infection

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