Role of lipopolysaccharide sialylation in serum resistance of serogroup B and C meningococcal disease isolates.
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ABSTRACT:
SUBMITTER: Vogel U
PROVIDER: S-EPMC96410 | biostudies-literature | 1999 Feb
REPOSITORIES: biostudies-literature
Publications
Role of lipopolysaccharide sialylation in serum resistance of serogroup B and C meningococcal disease isolates.
Vogel U U Claus H H Heinze G G Frosch M M
Infection and immunity 19990201 2
alpha-2,3-Sialyltransferase mutants of three genetically and phenotypically diverse Neisseria meningitidis strains were compared with regard to resistance to human serum and systemic spread in the infant rat. Lipopolysaccharide sialylation was found to be of minor importance for the resistance of serogroup B and C meningococcal disease isolates to complement attack. ...[more]
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Project description:BACKGROUND: Serogroup B meningococcal (MenB) isolates currently account for approximately 90% of invasive meningococcal disease (IMD) in Greece with ST-162 clonal complex predominating. The potential of a multicomponent meningococcal B vaccine (4CMenB) recently licensed in Europe was investigated in order to find whether the aforementioned vaccine will cover the MenB strains circulating in Greece. A panel of 148 serogroup B invasive meningococcal strains was characterized by multilocus sequence typing (MLST) and PorA subtyping. Vaccine components were typed by sequencing for factor H-binding protein (fHbp), Neisserial Heparin Binding Antigen (NHBA) and Neisseria adhesin A (NadA). Their expression was explored by Meningococcal Antigen Typing System (MATS). RESULTS: Global strain coverage predicted by MATS was 89.2% (95% CI 63.5%-98.6%) with 44.6%, 38.5% and 6.1% of strains covered by one, two and three vaccine antigens respectively. NHBA was the antigen responsible for the highest coverage (78.4%), followed by fHbp (52.7%), PorA (8.1%) and NadA (0.7%). The coverage of the major genotypes did not differ significantly. The most prevalent MLST genotype was the ST-162 clonal complex , accounting for 44.6% of the strains in the panel and with a predicted coverage of 86.4%, mainly due to NHBA and fHbp. CONCLUSIONS: 4CMenB has the potential to protect against a significant proportion of Greek invasive MenB strains.
| S-EPMC4018652 | biostudies-literature
Project description:In 2010, Burkina Faso completed the first nationwide mass-vaccination campaign of a meningococcal A conjugate vaccine, drastically reducing the incidence of disease caused by serogroup A meningococci. Since then, other strains, such as those belonging to serogroups W, X and C, have continued to cause outbreaks within the region. A carriage study was conducted in 2016 and 2017 in the country to characterize the meningococcal strains circulating among healthy individuals following the mass-vaccination campaign. Four cross-sectional carriage evaluation rounds were conducted in two districts of Burkina Faso, Kaya and Ouahigouya. Oropharyngeal swabs were collected for the detection of Neisseria meningitidis by culture. Confirmed N. meningitidis isolates underwent whole-genome sequencing for molecular characterization. Among 13 758 participants, 1035 (7.5 %) N. meningitidis isolates were recovered. Most isolates (934/1035; 90.2 %) were non-groupable and primarily belonged to clonal complex (CC) 192 (822/934; 88 %). Groupable isolates (101/1035; 9.8 %) primarily belonged to CCs associated with recent outbreaks in the region, such as CC11 (serogroup W) and CC10217 (serogroup C); carried serogroup A isolates were not detected. Phylogenetic analysis revealed several CC11 strains circulating within the country, several of which were closely related to invasive isolates. Three sequence types (STs) were identified among eleven CC10217 carriage isolates, two of which have caused recent outbreaks in the region (ST-10217 and ST-12446). Our results show the importance of carriage studies to track the outbreak-associated strains circulating within the population in order to inform future vaccination strategies and molecular surveillance programmes.
| S-EPMC8116689 | biostudies-literature
Project description:IntroductionInvasive meningococcal disease (IMD) is an important public health concern. In developed countries, most IMD is caused by meningococcal serogroup B (MenB) and two protein-based MenB vaccines are currently available: the four-component vaccine 4CMenB (Bexsero, GSK) and the bivalent vaccine MenB-FHbp (Trumenba, Pfizer). Genes encoding the 4CMenB vaccine antigens are also present in strains belonging to other meningococcal serogroups.MethodsTo evaluate the potential of 4CMenB vaccination to protect adolescents against non-MenB IMD, we tested the bactericidal activity of sera from immunized adolescents on 147 (127 European and 20 Brazilian) non-MenB IMD isolates, with a serum bactericidal antibody assay using human complement (hSBA). Serum pools were prepared using samples from randomly selected participants in various clinical trials, pre- and post-vaccination: 12 adolescents who received two doses of 4CMenB 2 months apart, and 10 adolescents who received a single dose of a MenACWY conjugate vaccine (as positive control).Results4CMenB pre-immune sera killed 7.5% of the 147 non-MenB isolates at hSBA titers ≥ 1:4. In total, 91 (61.9%) tested isolates were killed by post-dose 2 pooled sera at hSBA titers ≥ 1:4, corresponding to 44/80 (55.0%) MenC, 26/35 (74.3%) MenW, and 21/32 (65.6%) MenY isolates killed.Conclusion4CMenB vaccination in adolescents induces bactericidal killing of non-MenB isolates, suggesting that mass vaccination could impact IMD due to serogroups other than MenB.
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Project description:Three group B Neisseria meningitidis isolates, recovered from meningococcal disease cases in Canada and typed as B:2c:P1.5, were characterized. Multilocus sequence typing showed that all three isolates were related because of an identical sequence type (ST) 573. Isolates typed as 2c:P1.5 are common in serogroup Y meningococci but rare in isolates from serogroups B or C. Although no serogroup Y isolates have been typed as ST-573, eight isolates showed five to six housekeeping gene alleles that were identical to that of ST-573. This suggested that the B:2c:P1.5 isolates may have originated from serogroup Y organisms, possibly by capsule switching.
| S-EPMC2095022 | biostudies-other
Project description:Invasive meningococcal disease (IMD) is a major public health concern because of its high case fatality, long-term morbidity, and potential to course with outbreaks. IMD caused by Nesseira meningitidis serogroup B has been predominant in different regions of the world like Europe and only recently broadly protective vaccines against B serogroup have become available. Two protein-based vaccines, namely 4CMenB (Bexsero®) and rLP2086 (Trumenba®) are currently licensed for use in different countries against MenB disease. These vaccines came from a novel technology on vaccine design (or antigen selection) using highly specific antigen targets identified through whole-genome sequence analysis. Moreover, it has the potential to confer protection against non-B meningococcus and against other Neisserial species such as gonococcus. Real-world data on the vaccine-use are rapidly accumulating from the UK and other countries which used the vaccine for control of outbreak or as part of routine immunization program, reiterating its safety and efficacy. Additional data on real-life effectiveness, long-term immunity, and eventual herd effects, including estimates on vaccine impact for cost-effectiveness assessment are further needed. Given the predominance of MenB in Europe and other parts of the world, these new vaccines are crucial for the prevention and public health control of the disease, and should be considered.
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Project description:Invasive meningococcal disease is mainly caused by Neisseria meningitidis serogroups A, B, C, X, W, and Y. The serogroup is typically determined by slide agglutination serogrouping (SASG) and real-time PCR (RT-PCR). We describe a whole-genome sequencing (WGS)-based method to characterize the capsule polysaccharide synthesis (cps) locus, classify N. meningitidis serogroups, and identify mechanisms for nongroupability using 453 isolates from a global strain collection. We identified novel genomic organizations within functional cps loci, consisting of insertion sequence (IS) elements in unique positions that did not disrupt the coding sequence. Genetic mutations (partial gene deletion, missing genes, IS insertion, internal stop, and phase-variable off) that led to nongroupability were identified. The results of WGS and SASG were in 91% to 100% agreement for all serogroups, while the results of WGS and RT-PCR showed 99% to 100% agreement. Among isolates determined to be nongroupable by WGS (31 of 453), the results of all three methods agreed 100% for those without a capsule polymerase gene. However, 61% (WGS versus SASG) and 36% (WGS versus RT-PCR) agreements were observed for the isolates, particularly those with phase variations or internal stops in cps loci, which warrant further characterization by additional tests. Our WGS-based serogrouping method provides comprehensive characterization of the N. meningitidis capsule, which is critical for meningococcal surveillance and outbreak investigations.
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Project description:BackgroundThe conjugate vaccine against serogroup A Neisseria meningitidis (NmA), MenAfriVac, was first introduced in mass vaccination campaigns of the 1-29-year-olds in Burkina Faso in 2010. The aim of this study was to genetically characterize meningococcal isolates circulating in Burkina Faso before and up to 13 months after MenAfriVac mass vaccination.MethodsA total of 1,659 meningococcal carriage isolates were collected in a repeated cross-sectional carriage study of the 1-29-year-olds in three districts of Burkina Faso in 2010 and 2011, before and up to 13 months after mass vaccination. Forty-two invasive isolates were collected through the national surveillance in Burkina Faso in the same period. All the invasive isolates and 817 carriage isolates were characterized by serogroup, multilocus sequence typing and porA-fetA sequencing.ResultsSeven serogroup A isolates were identified, six in 2010, before vaccination (4 from carriers and 2 from patients), and one in 2011 from an unvaccinated patient; all were assigned to sequence type (ST)-2859 of the ST-5 clonal complex. No NmA carriage isolate and no ST-2859 isolate with another capsule were identified after vaccination. Serogroup X carriage and disease prevalence increased before vaccine introduction, due to the expansion of ST-181, which comprised 48.5% of all the characterized carriage isolates. The hypervirulent serogroup W ST-11 clone that was responsible for most of meningococcal disease in 2011 and 2012 was not observed in 2010; it appeared during the epidemic season of 2011, when it represented 40.6% of the serogroup W carriage isolates.ConclusionsSuccessive clonal waves of ST-181 and ST-11 may explain the changing epidemiology in Burkina Faso after the virtual disappearance of NmA disease and carriage. No ST-2859 strain of any serogroup was found after vaccination, suggesting that capsule switching of ST-2859 did not occur, at least not during the first 13 months after vaccination.
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Project description:Neisseria meningitidis serogroup B (MnB) is a leading cause of invasive meningococcal disease in adolescents and young adults. A recombinant factor H binding protein (fHBP) vaccine (Trumenba(®); bivalent rLP2086) was recently approved in the United States in individuals aged 10-25 years. Immunogenicity and safety of 2- or 3-dose schedules of bivalent rLP2086 were assessed in adolescents.Healthy adolescents (11 to <19 years) were randomized to 1 of 5 bivalent rLP2086 dosing regimens (0,1,6-month; 0,2,6-month; 0,2-month; 0,4-month; 0,6-month). Immunogenicity was assessed by serum bactericidal antibody assay using human complement (hSBA). Safety assessments included local and systemic reactions and adverse events.Bivalent rLP2086 was immunogenic when administered as 2 or 3 doses; the most robust hSBA responses occurred with 3 doses. The proportion of subjects with hSBA titers ?1:8 after 3 doses ranged from 91.7% to 95.0%, 98.9% to 99.4%, 88.4% to 89.0%, and 86.1% to 88.5% for MnB test strains expressing vaccine--heterologous fHBP variants A22, A56, B24, and B44, respectively. After 2 doses, responses ranged from 90.8% to 93.5%, 98.4% to 100%, 69.1% to 81.1%, and 70.1% to 77.5%. Geometric mean titers (GMTs) were highest among subjects receiving 3 doses and similar between the 2- and 3-dose regimens. After 2 doses, GMTs trended numerically higher among subjects with longer intervals between the first and second dose (6 months vs 2 and 4 months). Bivalent rLP2086 was well tolerated.Bivalent rLP2086 was immunogenic and well tolerated when administered in 2 or 3 doses. Three doses yielded the most robust hSBA response rates against MnB strains expressing vaccine-heterologous subfamily B fHBPs.
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Project description: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's 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 ?3 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.
| S-EPMC7902841 | biostudies-literature
Project description:The Legionella pneumophila TF3/1 mutant of the Corby strain, which possesses a point mutation in the active site of the O-acetyltransferase, synthesized the polysaccharide chain with a reduced degree of substitution with O-acetyl groups. The mutant did not produce a high-molecular-weight lipopolysaccharide (LPS) fraction above 12 kDa. The disturbances in LPS synthesis have an effect on the composition of other macromolecules (lipids and proteins), as indicated by differences in the infrared absorption spectra between the L. pneumophila Corby strain and its TF3/1 mutant. The wild-type strain contained less N+-CH3 and C-N groups as well as more CH3 groups than the mutant. The fatty acid composition showed that the wild type strain synthesized more branched acyl residues (a15:0, i16:0, and a17:0), a less unsaturated acid (16:1), and a straight-chain acid (18:0) than the mutant. The mutant synthesized approximately twice more a long-chain fatty acid (20:0) than the wild type. The main differences in the phospholipids between both strains were found in the classes of phosphatidylcholines and phosphatidylglycerols (PG). Substantial differences in the cell surface topography of these bacteria and their nanomechanical properties were shown by atomic force microscopy (AFM). The wild type strain had no undulated surface and produced numerous vesicles. In the case of the mutant type, the vesicles were not numerous, but there were grooves on the cell surface. The average roughness of the cell surface of the mutant was approximately twofold higher than in the wild-type strain. In turn, the wild-type strain exhibited much better adhesive properties than the mutant. The kinetic study of the interaction between the L. pneumophila strains and Acanthamoeba castellanii monitored by Förster resonance energy transfer revealed a pronounced difference, i.e., almost instantaneous and highly efficient binding of the L. pneumophila Corby strain to the amoeba surface, followed by penetration into the amoeba cells. This process was clearly not as efficient in the case of the mutant. The results point to LPS and, in particular, to the length of the polysaccharide fraction as an important L. pneumophila determinant involved in the process of adhesion to the host cell.
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