Survey of pediatricians in Germany reveals important challenges for possible implementation of meningococcal B vaccination

Incidence of invasive meningococcal disease is low in Germany at 0.5 cases/100,000 inhabitants. Serogroup B (MenB) is most common, causing 70% of cases, with highest incidence in infants (5.9/100,000). In 2013, a MenB vaccine was licensed in Europe. To assess pediatricians’ attitudes towards MenB vaccination and its potential use in Germany we conducted a nationwide cross-sectional survey among 5677 pediatricians. Of 3107 participants (response: 55%), 79.1% would recommend a MenB vaccination to parents, with 66.7% favoring a schedule at 6, 8 and 12 months over 2, 3, 4 and 12 months (13.4%). Administration separately from other vaccines was preferred (63.2%); 38.5% feared that a recommendation would lead to refusal of other recommended vaccinations. In conclusion, pediatricians showed distinct preferences regarding possible integration of MenB vaccination into the existent immunization schedule. As physicians play a crucial role in the implementation, findings will be useful in decision-making regarding potential introduction.     

A broadly-protective vaccine against meningococcal disease in sub-Saharan Africa based on Generalized Modules for Membrane Antigens (GMMA)

Introduction

Neisseria meningitidis causes epidemics of meningitis in sub-Saharan Africa. These have mainly been caused by capsular group A strains, but W and X strains are increasingly contributing to the burden of disease. Therefore, an affordable vaccine that provides broad protection against meningococcal disease in sub-Saharan Africa is required.

Methods

We prepared Generalized Modules for Membrane Antigens (GMMA) from a recombinant serogroup W strain expressing PorA P1.5,2, which is predominant among African W isolates. The strain was engineered with deleted capsule locus genes, lpxL1 and gna33 genes and over-expressed fHbp variant 1, which is expressed by the majority of serogroup A and X isolates.

Results

We screened nine W strains with deleted capsule locus and gna33 for high-level GMMA release. A mutant with five-fold increased GMMA release compared with the wild type was further engineered with a lpxL1 deletion and over-expression of fHbp. GMMA from the production strain had 50-fold lower ability to stimulate IL-6 release from human PBMC and caused 1000-fold lower TLR-4 activation in Human Embryonic Kidney cells than non-detoxified GMMA. In mice, the GMMA vaccine induced bactericidal antibody responses against African W strains expressing homologous PorA and fHbp v.1 or v.2 (geometric mean titres [GMT] = 80,000–200,000), and invasive African A and X strains expressing a heterologous PorA and fHbp variant 1 (GMT = 20–2500 and 18–5500, respectively). Sera from mice immunised with GMMA without over-expressed fHbp v.1 were unable to kill the A and X strains, indicating that bactericidal antibodies against these strains are directed against fHbp.

Conclusion

A GMMA vaccine produced from a recombinant African N. meningitidis W strain with deleted capsule locus, lpxL1, gna33 and overexpressed fHbp v.1 has potential as an affordable vaccine with broad coverage against strains from all main serogroups currently causing meningococcal meningitis in sub-Saharan Africa.     

Preclinical immunogenicity study of trivalent meningococcal AWX-OMV vaccines for the African meningitis belt

In the recent decade, epidemic meningitis in the African meningitis belt has mostly been caused by Neisseria meningitidis of serogroups A, W and X (MenA, MenW and MenX, respectively). There is at present no licensed vaccine available to prevent MenX meningococcal disease. To explore a trivalent MenAWX vaccine concept, we have studied the immunogenicity in mice of MenX outer membrane vesicles (X-OMV) or MenX polysaccharide (X-PS) when combined with a bivalent A-OMV and W-OMV (AW-OMV) vaccine previously shown to be highly immunogenic in mice. The vaccine antigens were produced from three representative wild type strains of MenA (ST-7), MenW (ST-11) and MenX (ST-751) isolated from patients in the African meningitis belt. Groups of mice were immunized with two doses of X-OMV or X-PS combined with the AW-OMV vaccine or as individual components. All vaccine preparations were adsorbed to Al(OH)₃. Sera from immunized mice were tested by ELISA and immunoblotting. Functional antibody responses were measured as serum bactericidal activity (SBA) and opsonophagocytic activity (OPA). Immunization of mice with X-OMV, alone or in combination with AW-OMV induced high levels of anti-X OMV IgG. Moreover, X-OMV alone or in combination with the AW-OMV vaccine induced high SBA and OPA titers against the MenX target strain. X-PS alone was not immunogenic in mice; however, addition of the AW-OMV vaccine to X-PS increased the immunogenicity of X-PS. Both AWX vaccine formulations induced high levels of IgG against A- and W-OMV and high SBA titers against the MenA and MenW vaccine strains. These results suggest that a trivalent AWX vaccine, either as a combination of OMV or OMV with X-PS, could potentially prevent the majority of meningococcal disease in the meningitis belt.     

A randomized,phase 1/2 trial of the safety,tolerability, and immunogenicity of bivalent rLP2086 meningococcal B vaccine in healthy infants

Background

Neisseria meningitidis serogroup B (MnB) is a major cause of invasive meningococcal disease in infants. A conserved, surface-exposed lipoprotein, LP2086 (a factor H-binding protein [fHBP]), is a promising MnB vaccine target. A bivalent, recombinant vaccine targeting the fHBP (rLP2086) of MnB was developed.

Methods

This phase 1/2 clinical study was designed to assess the immunogenicity, safety, and tolerability of a 4-dose series of the rLP2086 vaccine at 20-, 60-, 120-, or 200-μg dose levels in vaccine-naive infants when given with routine childhood vaccines. The study was to consist of two phases: a single-blind sentinel phase and an open-label full enrollment phase. During the sentinel phase, randomization of subjects to the next higher dose was delayed pending a 14-day safety review of dose 1 of the preceding dose cohort. The full enrollment phase was to occur after completion of the sentinel phase.

Results

Local reactions were generally mild and adverse events infrequent; however, after only 46 infants were randomized into the study, fever rates were 64% and 90% in subjects receiving one 20- or 60-μg rLP2086 dose, respectively. Most fevers were <39.0 °C. Only 2 subjects in the 20-μg group and 1 subject in the 60-μg group experienced fevers >39.0 °C; no fevers were >40.0 °C. Due to these high fever rates, the study was terminated early. No immunogenicity data were collected. This report discusses the safety and acceptability of rLP2086 in infants after one 20- or 60-μg dose.

Conclusion

Due to the high fever rate experienced in the 20- and 60-μg groups, rLP2086 in the current formulation may not be acceptable for infants.     

Neisseria gonorrhoeae cervical spine epidural abscess requiring spinal decompression and instrumented fusion

Disseminated gonococcal infection (DGI) is an uncommon complication of Neisseria gonorrhoeae infection, and typically presents with either a triad of tenosynovitis, dermatitis and polyarthralgia, or with extra-axial large joint septic arthritis. Spinal epidural abscess is a rare manifestation of DGI, with only a few previously reported cases, none of which required placement of metalware into the infected space. Here we report a severe case of isolated N. gonorrhoeae cervical spine epidural abscess necessitating surgical source control (C7/T1 laminectomy and debridement) and metalware placement (C6-T2 posterior instrumented fusion). The case was successfully managed by a combination of surgical intervention followed by six weeks of predominantly oral, targeted antimicrobial therapy.     

Immuno-proteomic analysis of human immune responses to experimental Neisseria meningitidis outer membrane vesicle vaccines identifies potential cross-reactive antigens

Human volunteers were vaccinated with experimental Neisseria meningitidis serogroup B vaccines based on strain H44/76 detoxified L3 lipooligosaccharide (LOS)-derived outer membrane vesicles (OMV) or the licensed Cuban vaccine, VA-MENGOC-BC. Some volunteers were able to elicit cross-bactericidal antibodies against heterologous L2-LOS strain (760676). An immuno-proteomic approach was used to identify potential targets of these cross-bactericidal antibodies using an L2-LOS derived OMV preparation. A total of nine immuno-reactive spots were detected in this proteome: individuals vaccinated with the detoxified OMVs showed an increase in post-vaccination serum reactivity with Spots 2–8, but not with Spots 1 and 9. Vaccination with VA-MENGOC-BC induced sera that showed increased reactivity with all of the protein spots. Vaccinees showed increases in serum bactericidal activity (SBA) against the heterologous L2-LOS expressing strain 760676, which correlated, in general, with immunoblot reactivity. The identities of proteins within the immuno-reactive spots were determined. These included not only well-studied antigens such as Rmp, Opa, PorB and FbpA (NMB0634), but also identified novel antigens such as exopolyphosphatase (NMB1467) and γ-glutamyltranspeptidase (NMB1057) enzymes and a putative cell binding factor (NMB0345) protein. Investigating the biological properties of such novel antigens may provide candidates for the development of second generation meningococcal vaccines.     

韶关市2009—2011年健康人群C群脑膜炎奈瑟菌血清杀菌力抗体检测结果分析

目的了解韶关市健康人群血清C群脑膜炎奈瑟菌杀菌力水平,以评价健康人群对C群脑膜炎奈瑟菌的保护水平。方法2009—2011年,每年随机抽取8个年龄组健康人群血清共计811份,采用血清杀菌力试验检测血清中杀菌力抗体水平。结果811份健康人群血清中C群脑膜炎奈瑟菌杀菌力抗体总阳性率为25．40％,总保护率为23．06％,GNT为l：5．13,95％置信区间1：4．57～1：5．89。结论韶关市健康人群对c群脑膜炎奈瑟菌的传染有易感性,年龄越低其对C群脑膜炎奈瑟菌的抵抗力越弱,应加大对A＋C群流脑疫苗宣传力度,普及适龄儿童A＋C群流脑疫苗的免疫接种。     

Zapobieganie zakażeniom meningokokowym – jak stosować obecnie dostępne szczepionki

Authors have presented the current recommendations for the prevention of meningococcal infections. The epidemiological situation in Poland has been described and the use of currently available meningococcal vaccines has been discussed. The chemoprophylaxis for close contacts of all people with invasive meningococcal disease has been also presented.     

Performance of cobas® 4800 and m2000 real-time™ assays for detection of Chlamydia trachomatis and Neisseria gonorrhoeae in rectal and self-collected vaginal specimen

A prospective, multicenter trial was designed to compare the performance characteristics of the cobas® 4800 (Roche Diagnostics, Indianapolis, IN, USA) and m2000 real-time™ (Abbott Molecular Inc., Des Plaines, IL, USA) assays for detection of Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) in rectal and self-collected vaginal swabs. Rectal (n = 234) or self-collected vaginal swabs (n = 687) were obtained from consenting individuals visiting their general practitioners, dermatologists, gynecologists, sexually transmitted disease clinics, or family planning centers from May 2010 to February 2011. High concordance rates (≥96%) were observed between the cobas® 4800 and m2000 real-time™ assays for CT/NG detection in both rectal and self-collected vaginal swabs. The performance profiles confirm the usefulness of both kinds of swab types for CT and NG detection using described nucleic acid amplification tests assays. Based on this study, rectal and self-collected vaginal swabs offer a noninvasive alternative, which may improve screening for CT and NG infections.     

Serogroup C Neisseria meningitidis invasive infection: analysis of the possible vaccination strategies for a mass campaign

The serogroup C meningococcal conjugate vaccine is available since 1999. In the absence of randomized controlled trials that support a specific schedule, each country has adopted different vaccination programmes. Hereby, we analyse positive and negative aspects of the different vaccination strategies. Conclusion: While waiting for the introduction of other antimeningococcal vaccines, covering also for the Group B meningococci, further studies on effectiveness of an optimal schedule to be adopted in European countries are needed.