Experimental disease models for the assessment of meningococcal vaccines

Gorringe, Andrew; Reddin, Karen M.; Funnell, Simon G. P.; Johansson, Linda; Rytkönen, Anne; Jonsson, Ann‐Beth

doi:10.1016/j.vaccine.2005.01.053

Cited by 32 publications

(24 citation statements)

References 9 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…34 Laboratory and assay considerations in assessment of persistence against serogroup A Antibody decay rates also depend on the serological assay used for measurement of antibody titers. Several types of serological assays have historically been used for assessment of meningococcal antigen-specific immunity, including assays that measure complement-mediated bacterial killing using endogenous and exogenous complement (rabbit or human), anti-capsular antibody levels, or opsonophagocytosis, 35 and assays using different animal protection models. [36][37][38] Although the hSBA assay is the most commonly used serologic marker of protection, this assay is difficult to standardize due to the nature of the reagents used.…”

Section: Rapid Waning Of Serogroup a Responses After Single Or Multipmentioning

confidence: 99%

“…35 Both of these assays are exquisitely sensitive, although technically challenging, and adapting these assays for testing the large number of clinical samples typically generated in a vaccine trial is not feasible. An alternative opsonophagocytic assay platform which could potentially be adopted for higher throughput of clinical samples is a flow cytometry-based assay with the opsonophagocytic activity of the serum antibodies measured as respiratory burst; this assay also using live meningococci as the target cells and human polymorphonuclear neutrophils (PMNs) from donors.…”

Section: Rapid Waning Of Serogroup a Responses After Single Or Multipmentioning

confidence: 99%

See 1 more Smart Citation

Persistence of the immune response after MenACWY-CRM vaccination and response to a booster dose, in adolescents, children and infants

Baxter

Keshavan

Welsch

et al. 2016

Human Vaccines & Immunotherapeutics

View full text Add to dashboard Cite

Persistence of bactericidal antibodies following vaccination is extremely important for protection against invasive meningococcal disease, given the epidemiology and rapid progression of meningococcal infection. We present an analysis of antibody persistence and booster response to MenACWY-CRM, in adolescents, children and infants, from 7 clinical studies. Immunogenicity was assessed using the serum bactericidal assay with both human and rabbit complement. Post-vaccination hSBA titers were high, with an age-and serogroup-specific decline in titers up to 1 y and stable levels up to 5 y The waning of hSBA titers over time was more pronounced among infants and toddlers and the greatest for serogroup A. However, rSBA titers against serogroup A were consistently higher and showed little decline over time, suggesting that protection against this serogroup may be sustained. A single booster dose of MenACWY-CRM administered at 3 to 5 y induced a robust immune response in all age groups.

show abstract

Section: Rapid Waning Of Serogroup a Responses After Single Or Multipmentioning

confidence: 99%

Section: Rapid Waning Of Serogroup a Responses After Single Or Multipmentioning

confidence: 99%

Persistence of the immune response after MenACWY-CRM vaccination and response to a booster dose, in adolescents, children and infants

Baxter

Keshavan

Welsch

et al. 2016

Human Vaccines & Immunotherapeutics

View full text Add to dashboard Cite

show abstract

“…The model established in the rat is based on i.p. injection of neonatal animals with rat-passaged meningococci to increase bacterial virulence (40), and it has largely been used in vaccine studies (14,41,59). Mouse models of meningococcal disease are generally based on administration of an exogenous iron source to animals prior to infection in order to favor bacterial multiplication in the host (17,42).…”

mentioning

confidence: 99%

The Meningococcal ABC-Type l -Glutamate Transporter GltT Is Necessary for the Development of Experimental Meningitis in Mice

Colicchio

Ricci²,

Lamberti

et al. 2009

Infect Immun

View full text Add to dashboard Cite

Experimental animal models of bacterial meningitis are useful to study the host-pathogen interactions occurring at the cerebral level and to analyze the pathogenetic mechanisms behind this life-threatening disease. In this study, we have developed a mouse model of meningococcal meningitis based on the intracisternal inoculation of bacteria. Experiments were performed with mouse-passaged serogroup C Neisseria meningitidis. Survival and clinical parameters of infected mice and microbiological and histological analysis of the brain demonstrated the establishment of meningitis with features comparable to those of the disease in humans. When using low bacterial inocula, meningococcal replication in the brain was very efficient, with a 1,000-fold increase of viable counts in 18 h. Meningococci were also found in the blood, spleens, and livers of infected mice, and bacterial loads in different organs were dependent on the infectious dose. As glutamate uptake from the host has been implicated in meningococcal virulence, mice were infected intracisternally with an isogenic strain deficient in the ABC-type L-glutamate transporter GltT. Noticeably, the mutant was attenuated in virulence in mixed infections, indicating that wild-type bacteria outcompeted the GltT-deficient meningococci. The data show that the GltT transporter plays a role in meningitis and concomitant systemic infection, suggesting that meningococci may use L-glutamate as a nutrient source and as a precursor to synthesize the antioxidant glutathione.

show abstract

“…The antigens selected by reverse vaccinology were prioritized based on their ability to induce broad protection as inferred by BCA or observed in passive protection in the infant rat or mouse protection assays (19,20). The three top antigens that met the prioritization criteria were GNA2132 (21), GNA1870 (16,22,23), and NadA (17,24).…”

Section: Resultsmentioning

confidence: 99%

“…The presence of BCA was tested in sera obtained by immunizing mice with each of the antigens formulated with aluminum hydroxide or FCA (Table 1). With the exception of GNA2091, which, although unable to induce BCA, had been selected for its ability to induce protection in the mouse protection assay (19,20) (data not shown), each of the other individual antigens induced BCA against one or more of the three strains. The proteins GNA2132, GNA1030, and GNA1870 induced better titers when formulated with FCA than when formulated with aluminum.…”

Section: Resultsmentioning

confidence: 99%

A Universal Vaccine for Serogroup B Meningococcus

2007

Pediatric Infectious Disease Journal

View full text Add to dashboard Cite

Meningitis and sepsis caused by serogroup B meningococcus are two severe diseases that still cause significant mortality. To date there is no universal vaccine that prevents these diseases. In this work, five antigens discovered by reverse vaccinology were expressed in a form suitable for large-scale manufacturing and formulated with adjuvants suitable for human use. The vaccine adjuvanted by aluminum hydroxide induced bactericidal antibodies in mice against 78% of a panel of 85 meningococcal strains representative of the global population diversity. The strain coverage could be increased to 90% and above by the addition of CpG oligonucleotides or by using MF59 as adjuvant. The vaccine has the potential to conquer one of the most devastating diseases of childhood.meningococcus B ͉ reverse vaccinology

show abstract

Experimental disease models for the assessment of meningococcal vaccines

Cited by 32 publications

References 9 publications

Persistence of the immune response after MenACWY-CRM vaccination and response to a booster dose, in adolescents, children and infants

Persistence of the immune response after MenACWY-CRM vaccination and response to a booster dose, in adolescents, children and infants

The Meningococcal ABC-Type l -Glutamate Transporter GltT Is Necessary for the Development of Experimental Meningitis in Mice

A Universal Vaccine for Serogroup B Meningococcus

Contact Info

Product

Resources

About