Enhanced Timeliness and Co-Administration of Meningitis B Vaccination in Children: Impact of Funding in Valencian Community, Spain.

Public funding of vaccines may enhance vaccination rates, co-administration, and timeliness. The impacts of including the serogroup B meningococcus vaccine (MenB) into the national immunisation schedule on vaccination rates, co-administration rates, and timeliness were assessed using a population-based pre-funding (2022) and post-funding (2023) study design. MenB vaccination rates improved after funding and were in line with previously funded vaccines. Co-administration rates also increased significantly. Timely administration increased, protecting children at an early age. Public funding has a positive impact on vaccine accessibility and early protection. Consistent population characteristics highlight the role of funding.

Serogroup B Invasive Meningococcal Disease in Older Adults Identified by Genomic Surveillance, England, 2022-2023.

We report a cluster of serogroup B invasive meningococcal disease identified via genomic surveillance in older adults in England and describe the public health responses. Genomic surveillance is critical for supporting public health investigations and detecting the growing threat of serogroup B Neisseria meningitidis infections in older adults.

Bioinformatics Analysis of Global Diversity in Meningococcal Vaccine Antigens over the Past 10 Years: Vaccine Efficacy Prognosis.

Neisseria meningitidis (N. meningitidis) serogroup B (MenB) is the leading cause of invasive meningococcal disease worldwide. The pathogen has a wide range of virulence factors, which are potential vaccine components. Studying the genetic variability of antigens within a population, especially their long-term persistence, is necessary to develop new vaccines and predict the effectiveness of existing ones. The multicomponent 4CMenB vaccine (Bexsero), used since 2014, contains three major genome-derived recombinant proteins: factor H-binding protein (fHbp), Neisserial Heparin-Binding Antigen (NHBA) and Neisserial adhesin A (NadA). Here, we assessed the prevalence and sequence variations of these vaccine antigens in a panel of 5667 meningococcal isolates collected worldwide over the past 10 years and deposited in the PubMLST database. Using multiple amino acid sequence alignments and Random Forest Classifier machine learning methods, we estimated the potential strain coverage of fHbp and NHBA vaccine variants (51 and about 25%, respectively); the NadA antigen sequence was found in only 18% of MenB genomes analyzed, but cross-reactive variants were present in less than 1% of isolates. Based on our findings, we proposed various strategies to improve the 4CMenB vaccine and broaden the coverage of N. meningitidis strains.

Meningococcal B Immunisation in Adults and Potential Broader Immunisation Strategies: A Narrative Review.

Recombinant vaccines against invasive meningococcal disease due to Neisseria meningitidis serogroup B (MenB) have shown substantial impact in reducing MenB disease in targeted populations. 4CMenB targets four key N. meningitidis protein antigens; human factor H binding protein (fHbp), Neisserial heparin binding antigen (NHBA), Neisseria adhesin A (NadA) and the porin A protein (PorA P1.4), with one or more of these expressed by most pathogenic MenB strains, while MenB-FHbp targets two distinct fHbp variants. While many countries recommend MenB immunisation in adults considered at high risk due to underlying medical conditions or immunosuppression, there are no recommendations for routine use in the general adult population. We reviewed the burden of MenB in adults, where, while incidence rates remain low (and far lower than in young children < 5 years of age at greatest risk), a substantial proportion of MenB cases (20% or more) is now observed in the adult population; evident in Europe, Australia, and in the United States. We also reviewed immunogenicity data in adults from clinical studies conducted during MenB vaccine development and subsequent post-licensure studies. A 2-dose schedule of 4CMenB generates hSBA titres ≥ 1:4 towards all four key vaccine target antigens in up to 98-100% of subjects. For MenB-FHbp, a ≥ fourfold rise in hSBA titres against the four primary representative test strains was observed in 70-95% of recipients following a 3-dose schedule. While this suggests potential benefits for MenB immunisation if used in adult populations, data are limited (especially for adults > 50 years) and key aspects relating to duration of protection remain unclear. Although a broader adult MenB immunisation policy could provide greater protection of the adult population, additional data are required to support policy decision-making.

Safety surveillance of meningococcal group B vaccine (Bexsero®), Vaccine Adverse Event Reporting System, 2015-2018.

BACKGROUND: Bexsero® (GlaxoSmithKline) is a four-component Neisseria meningitidis serogroup B vaccine (MenB-4C). It was licensed in the United States in 2015 for use among individuals ages 10-25 years. We aimed to assess the post-licensure safety profile of MenB-4C by examining reports received in the Vaccine Adverse Event Reporting System (VAERS). METHODS: VAERS is a national passive surveillance system for adverse events (AEs) following immunization that uses the Medical Dictionary for Regulatory Activities to code reported AEs and the Code of Federal Regulations to classify reports by seriousness. In this case series, we analyzed U.S. reports involving MenB-4C received between January 23, 2015 through December 31, 2018. We used Empirical Bayesian data mining to identify MenB-4C/AE combinations reported at least twice as often as expected. RESULTS: VAERS received 1,867 reports following MenB-4C administration, representing 332 reports per million doses distributed. Most reports were for females (59%), with a median age of 17 years (interquartile range: 16-18 years); 40% of reports described simultaneous administration of other vaccines. The majority of reports were classified as non-serious (96%). The most commonly reported AEs were injection site pain (22%), pyrexia (16%), and headache (16%). Data mining identified disproportionate reporting for "injected limb mobility decreased" secondary to injection site reactions, including extensive swelling of the vaccinated limb and injection site pain. CONCLUSIONS: Analysis of passive surveillance data from over 5.6 million doses of MenB-4C distributed in the United States did not reveal new safety concerns. The large majority of reports were classified as non-serious and the reported AEs were generally consistent with the safety experience described in clinical studies and the product's package insert. While our results are reassuring, continued post-marketing surveillance is warranted.

Intranasal immunization with a rNMB0315 and combination adjuvants induces protective immunity against Neisseria meningitidis serogroup B in mice.

Neisseria meningitidis (N. meningitidis) is a human-specific pathogen and a major cause of meningitis and septicemia with a high case fatality rate. N. meningitidis may penetrate the nasopharyngeal mucosal membrane and cause severe meningitis, a mucosal immune response plays a key role in the defense against meningococcal infections. Our previous study demonstrated that N. meningitidis serogroup B 0315 (NMB0315) was a vaccine candidate against N. meningitidis serogroup B (NMB) through parenteral immunization. In this study, immunopotentiators (C48/80 or CpG-ODN) were loaded into chitosan nanoparticle (Chi NP) to form combination adjuvants (Chi-CpG NP and Chi-C48/80 NP) and adopted to enhance the immunogenicity of NMB0315 through intranasal immunization. The experimental results have indicated that both Chi-CpG NP and Chi-C48/80 NP are effective mucosal adjuvants for the induction of significantly higher rNMB0315-specific IgG, IgG1, IgG2a and sIgA antibodies. Meanwhile, Chi-CpG NP and Chi-C48/80 NP could change the ratio of IgG1/IgG2a, inducing a more balanced cellular/humoral immune response. Chi-CpG NP and Chi-C48/80 NP also boosted interleukin-4 (IL-4), interferon-γ (IFN-γ) and interleukin-17 A (IL-17A) production by splenocytes. The bactericidal antibodies have been detected in sera from mice immunized with rNMB0315 + Chi-CpG NP and rNMB0315 + Chi-C48/80 NP. Overall, the combination adjuvants could be applicable to the development of a mucosal vaccine against NMB.

Safety Surveillance of Bivalent Meningococcal Group B Vaccine, Vaccine Adverse Event Reporting System, 2014-2018.

BACKGROUND: In October 2014, MenB-FHbp (Trumenba, Pfizer) became the first meningococcal group B vaccine licensed in the United States. It is approved for use in individuals aged 10-25 years. Our objective was to evaluate the safety of MenB-FHbp postlicensure. METHODS: The Vaccine Adverse Event Reporting System (VAERS) is a national passive vaccine safety surveillance system. We analyzed US VAERS reports for MenB-FHbp received from the date of licensure in October 2014 through December 2018. We described the characteristics of the persons and adverse events (AEs) reported and calculated reporting rates using the number of doses distributed. We used empirical Bayesian data mining to identify AEs reported at least twice as often as expected compared with all other vaccines. RESULTS: VAERS received 2106 reports involving MenB-FHbp, representing 698 reports per million doses distributed. The median age of vaccinees was 17 years, and 55% were female. MenB-FHbp was given simultaneously with other vaccines in 37% of reports. Most reports (57%) described AEs that started on the day of or day after vaccination. The most common AEs reported were pyrexia (27%), headache (25%), and pain (16%). There were 44 serious reports (2% of all reports), among which 42 reported a hospitalization. Data mining identified disproportional reporting of headache, pyrexia, chills, and myalgia. CONCLUSIONS: The AEs most commonly or disproportionately reported following MenB-FHbp were consistent with those identified in clinical trials as described in the US package insert. We did not identify any new safety issues.

Randomized Trial of 2 Schedules of Meningococcal B Vaccine in Adolescents and Young Adults, Canada1.

Emergency vaccination programs often are needed to control outbreaks of meningococcal disease caused by Neisseria meningitidis serogroup B (MenB) on college campuses. Such campaigns expend multiple campus and public health resources. We conducted a randomized, controlled, multicenter, observer-blinded trial comparing immunogenicity and tolerability of an accelerated vaccine schedule of 0 and 21 days to a longer interval of 0 and 60 days for 4-component MenB vaccine (MenB-4C) in students 17-25 years of age. At day 21 after the first MenB-4C dose, we observed protective human serum bactericidal titers >4 to MenB strains 5/99, H44/76, and NZ 98/254 in 98%-100% of participants. Geometric mean titers increased >22-fold over baseline. At day 180, >95% of participants sustained protective titers regardless of their vaccine schedule. The most common adverse event was injection site pain. An accelerated MenB-4C immunization schedule could be considered for rapid control of campus outbreaks.

[Economic evaluation of the introduction of 4CMenB (Bexsero®) in the national vaccine schedule in Spain]. / Evaluación económica de la inclusión en el calendario vacunal de 4CMenB (Bexsero®) en España.

INTRODUCTION: Bexsero® (4CMenB), meningococcal B vaccine, was licensed in Europe in 2013. In Spain, despite MenB being the most frequent cause of invasive meningococcal disease (IMD), Bexsero® is recommended and financed for patients at increased risk of IMD but is not financed by the NHS in the routine vaccination schedule. OBJECTIVE: to evaluate the cost-utility, epidemiological impact, and total costs of the introduction of 4CMenB into the vaccination schedule to help inform vaccine policy in Spain. METHOD: We adapted a cost-utility analysis, a probabilistic decision-tree, to Spain. A cohort of new-born infants in 2015 was modelled with two dosages, using two different strategies: routine vaccination schedule with 4CMenB and non-vaccination. Costs were measured from a payer perspective and benefits were calculated in quality-adjusted life years (QALYs). A Monte Carlo analysis and 32 scenarios were performed to assess the robustness and the uncertainty of our results. RESULTS: With the 3+1 dosage, routine vaccination prevented 54% of cases and deaths and an incremental cost-utility ratio (ICUR) of 351.389 €/QALY (95% confidence interval [95%CI]: 265,193-538,428) was estimated. The 2+1 dosage prevented 50% of cases and deaths, with an ICUR of 278.556 €/QALY (95%CI: 210,285-430,122). CONCLUSIONS: Given the current incidence of invasive meningococcal disease in Spain and the information available from 4CMenB, our model shows that routine vaccination is not cost-effective at the current price. Only with a vaccine price of 1.45 € for the 3+1 schedule or 3.37 € for the 2+1 schedule could it be recommended based on efficiency criteria.

Phenotypic and genotypic characterization of meningococcal isolates in Tunis, Tunisia: High diversity and impact on vaccination strategies.

OBJECTIVES: The aim of this study was to characterize Neisseria meningitidis (Men) isolates in Tunisian paediatric patients with invasive meningococcal disease (IMD) in order to target therapeutic and preventive strategies. METHODS: Fifty-nine isolates of Men and four cerebrospinal fluid samples that were culture-negative but Men-positive by PCR (NC-MenPPCR) (2009-2016) were collected from IMD patients. Isolates were analysed for their antimicrobial susceptibility. Whole-genome sequencing (WGS) was used to characterize isolates and multilocus sequence typing for NC-MenPPCR. Coverage of Men serogroup B (MenB) was determined by Genetic Meningococcal Antigen Typing System (gMATS) and fHbp expression by ELISA. RESULTS: MenB was the predominant type (88.9%). The majority of isolates (81%) had reduced susceptibility to penicillin G with altered penA alleles. The clonal complex CC461 (27.1%) was the most frequent. Among the MenB vaccine targets neisserial heparin binding antigen (NHBA) and fHbp, the predominant variants were NHBA118 (30.8%) and fHbp peptide 47 (25%), respectively. The nadA gene was present in 17.3% of isolates. Using gMATS, 36.5% of MenB were predicted to be covered by the 4CMenB vaccine. ELISA showed that 92.4% of the MenB were expected to be killed by anti-fHbp antibodies. CONCLUSIONS: MenB was the leading serogroup in IMD, and more than 90% had a sufficient level of fHbp expression for vaccine coverage. The study results will be useful for the Tunisian vaccination programme.

Chimeric hepatitis B virus core particles displaying Neisserial surface protein A confer protection against virulent Neisseria meningitidis serogroup B in BALB/c mice.

PURPOSE: The primary goal of the present study was to explore and evaluate the highly conserved Neisserial surface protein A (NspA) molecule, fused with truncated HBV virus-like particles (VLPs), as a candidate vaccine against the virulent Neisseria meningitidis serogroup B (NMB). METHODS: NspA was inserted into the major immunodominant region of the truncated hepatitis B virus core protein (HBc; amino acids 1-144). The chimeric protein, HBc-N144-NspA, was expressed from a prokaryotic vector and generated HBc-like particles, as determined by transmission electron microscopy. Further, the chimeric protein and control proteins were used to immunize mice and the resulting immune responses evaluated by flow cytometry, enzyme-linked immunosorbent assay, and analysis of serum bactericidal activity (SBA) titer. RESULTS: Evaluation of the immunogenicity of the recombinant HBc-N144-NspA protein showed that it elicited the production of high levels of NspA-specific total IgG. The SBA titer of HBc-N144-NspA/F reached 1:16 2 weeks after the last immunization in BALB/c mice, when human serum complement was included in the vaccine. Immunization of HBc-N144-NspA, even without adjuvant, induced high levels of IL-4 and a high IgG1 to IgG2a ratio, confirming induction of an intense Th2 immune response. Levels of IL-17A increased rapidly in mice after the first immunization with HBc-N144-NspA, indicating the potential for this vaccine to induce a mucosal immune response. Meanwhile, the immunization of HBc-N144-NspA without adjuvant induced only mild inflammatory infiltration into the mouse muscle tissue. CONCLUSION: This study demonstrates that modification using HBc renders NspA a candidate vaccine, which can trigger protective immunity against NMB.

The Development of a Vaccine Against Meningococcus B Using Reverse Vaccinology.

The discovery of vaccine antigens through whole genome sequencing (WGS) contrasts with the classical hypothesis-driven laboratory-based analysis of microbes to identify components to elicit protective immunity. This radical change in scientific direction and action in vaccine research is captured in the term reverse vaccinology. The complete genome sequence of an isolate of Neisseria meningitidis serogroup B (MenB) was systematically analyzed to identify proteins predicted to be secreted or exported to the outer membrane. This identified hundreds of genes coding for potential surface-exposed antigens. These were amplified, cloned in expression vectors and used to immunize mice. Antisera against 350 recombinant antigens were obtained and analyzed in a panel of immunological assays from which 28 were selected as potentially protective based on the -antibody dependent, complement mediated- serum bactericidal activity assay. Testing of these candidate vaccine antigens, using a large globally representative strain collection of Neisseria species isolated from cases of disease and carriage, indicated that no single component would be sufficient to induce broad coverage and that a "universal" vaccine should contain multiple antigens. The final choice of antigens to be included was based on cross-protective ability, assayed by serum bactericidal activity and maximum coverage of the extensive antigenic variability of MenB strains. The resulting multivalent vaccine formulation selected consisted of three recombinant antigens (Neisserial Heparin Binding Antigen or NHBA, Factor H binding protein or fHbp and Neisseria Adhesin A or NadA). To improve immunogenicity and potential strain coverage, an outer membrane vesicle component obtained from the epidemic New Zealand strain (OMVNz) was added to the formulation to create a four component vaccine, called 4CMenB. A series of phase 2 and 3 clinical trials were conducted to evaluate safety and tolerability and to estimate the vaccine effectiveness of human immune responses at different ages and how these were affected by various factors including concomitant vaccine use and lot-to-lot consistency. 4CMenB was approved in Europe in 2013 and introduced in the National Immunization Program in the UK starting from September 2015 when the vaccine was offered to all newborns using a 2, 4, and 12 months schedule., The effectiveness against invasive MenB disease measured at 11 months after the study start and 5 months after the second vaccination was 83% and there have been no safety concerns.

[Molecular characteristics of serogroup B neisseria meningitidis, China].

Objective: To investigate the molecular characteristics of serogroup B neisseria meningitidis in China. Methods: Total of 485 (100 strains isolated from cerebrospinal fluid or blood samples of encephalomyelitis cases, and 385 strains isolated from nasopharynx of healthy carriers) Meningococcal serogroup B (MenB) strains, isolated from 29 provinces of China between 1968 and 2016, were analyzed by multilocus sequence typing (MLST) and PorA typing methods. Further, the genetic diversity of three MenB vaccine proteins, FHbp, NadA and NHBA, were analyzed. Results: The 485 study strains belonged to 270 sequence types (STs), 107 of which (representing 211 strains) could be grouped into ten clonal complexes (CC). CC4821 has been the predominant lineage in China since 2005 (28.7%, n=139). The most common PorA types of MenB strains from invasive meningococcal cases were P1.5-2,2-2 (10.0%, n=10), P1.5-1,2-2 (9.0%, n=9) and P1.5-1,10-4 (9.0%, n=9). Four hundred and twenty one strains had intact fhbp gene; variant 1, 2 and 3 accounted for 12.8% (54 strains), 85.0% (358 strains) and 2.2% (9 strains) respevtively. Ten out of 432 strains (2.3%) contained complete nadA gene. All the 172 strains for which the nhba gene was sequenced had intact gene sequence which corresponded to 68 peptide types. Conclusion: CC4821 was the predominant CC of MenB strains in China; the vaccine proteins were diverse about the sequences. The vaccine proteins should be carefully selected when developing MenB vaccines in China.

Genetic Meningococcal Antigen Typing System (gMATS): A genotyping tool that predicts 4CMenB strain coverage worldwide.

BACKGROUND: The Meningococcal Antigen Typing System (MATS) was developed to identify meningococcus group B strains with a high likelihood of being covered by the 4CMenB vaccine, but is limited by the requirement for viable isolates from culture-confirmed cases. We examined if antigen genotyping could complement MATS in predicting strain coverage by the 4CMenB vaccine. METHODS: From a panel of 3912 MATS-typed invasive meningococcal disease isolates collected in England and Wales in 2007-2008, 2014-2015 and 2015-2016, and in 16 other countries in 2000-2015, 3481 isolates were also characterized by antigen genotyping. Individual associations between antigen genotypes and MATS coverage for each 4CMenB component were used to define a genetic MATS (gMATS). gMATS estimates were compared with England and Wales human complement serum bactericidal assay (hSBA) data and vaccine effectiveness (VE) data from England. RESULTS: Overall, 81% of the strain panel had genetically predictable MATS coverage, with 92% accuracy and highly concordant results across national panels (Lin's accuracy coefficient, 0.98; root-mean-square deviation, 6%). England and Wales strain coverage estimates were 72-73% by genotyping (66-73% by MATS), underestimating hSBA values after four vaccine doses (88%) and VE after two doses (83%). The gMATS predicted strain coverage in other countries was 58-88%. CONCLUSIONS: gMATS can replace MATS in predicting 4CMenB strain coverage in four out of five cases, without requiring a cultivable isolate, and is open to further improvement. Both methods underestimated VE in England. Strain coverage predictions in other countries matched or exceeded England and Wales estimates.

Molecular characteristics of serogroup B neisseria meningitidis, China / 中华预防医学杂志

Objective@#To investigate the molecular characteristics of serogroup B neisseria meningitidis in China.@*Methods@#Total of 485 (100 strains isolated from cerebrospinal fluid or blood samples of encephalomyelitis cases, and 385 strains isolated from nasopharynx of healthy carriers) Meningococcal serogroup B (MenB) strains, isolated from 29 provinces of China between 1968 and 2016, were analyzed by multilocus sequence typing (MLST) and PorA typing methods. Further, the genetic diversity of three MenB vaccine proteins, FHbp, NadA and NHBA, were analyzed.@*Results@#The 485 study strains belonged to 270 sequence types (STs), 107 of which (representing 211 strains) could be grouped into ten clonal complexes (CC). CC4821 has been the predominant lineage in China since 2005 (28.7%, n=139). The most common PorA types of MenB strains from invasive meningococcal cases were P1.5-2,2-2 (10.0%, n=10), P1.5-1,2-2 (9.0%, n=9) and P1.5-1,10-4 (9.0%, n=9). Four hundred and twenty one strains had intact fhbp gene; variant 1, 2 and 3 accounted for 12.8% (54 strains), 85.0% (358 strains) and 2.2% (9 strains) respevtively. Ten out of 432 strains (2.3%) contained complete nadA gene. All the 172 strains for which the nhba gene was sequenced had intact gene sequence which corresponded to 68 peptide types.@*Conclusion@#CC4821 was the predominant CC of MenB strains in China; the vaccine proteins were diverse about the sequences. The vaccine proteins should be carefully selected when developing MenB vaccines in China.

Coinfección por astrovirus y Neisseria meningitidis serogrupo B en una niña / Coinfection by astrovirus and Neisseria B meningitidis in a girl

La infección meningocócica tiene una elevada morbimortalidad. Las coinfecciones virales han sido descritas, fundamentalmente, por virus herpes y respiratorios. Se presenta una paciente que ingresó al Servicio de Emergencia con convulsión tónico-clónica, hipotensión, taquicardia y escala de Glasgow posterior baja. En la Unidad de Cuidados Intensivos mantuvo alteración del nivel de conciencia y requirió estabilización hemodinámica. Se inició antibioterapia de amplio espectro. La paciente mostró deposiciones líquidas malolientes, sin sangre, que fueron cultivadas y estudiadas mediante reacción en cadena de la polimerasa. El líquido cefalorraquídeo fue normal. Las deposiciones resultaron positivas para astrovirus. Se confirmó, mediante reacción en cadena de la polimerasa en sangre, la presencia de Neisseria meningitidis serogrupo B. Se presenta el primer caso pediátrico de coinfección por astrovirus y Neisseria meningitidis. Este virus debería incluirse entre las causas de coinfección para descartar en caso de clínica abdominal predominante, vómitos o deposiciones líquidas.

Meningococcal infection associates high morbidity and mortality. Viral coinfection has been described mainly with herpes and respiratory virus. We describe a child who suffered a tonic-clonic seizure with hypotension, tachycardia and low Glasgow Coma Scale. She maintained an altered mental status and required hemodynamic stabilization in the Pediatric Intensive Care Unit. Wide spectrum antibiotherapy was initiated. She suffered large and foul-smelling liquid not bloody stools which were cultured and studied by polymerase chain reaction. The cerebrospinal fluid was normal. Later the polymerase chain reaction stools were positive to astrovirus, and the blood polymerase chain reaction was positive to Neisseria meningitidis group B. As far as we know, this is the first case of astrovirus and Neisseria meningitidis coinfection described in children. This virus should be considered as new cause of viral coinfection to discard if unexplained abdominal pain or vomits and liquid stools are observed.

[Coinfection by astrovirus and Neisseria B meningitidis in a girl]. / Coinfección por astrovirus y Neisseria meningitidis serogrupo B en una niña.

Meningococcal infection associates high morbidity and mortality. Viral coinfection has been described mainly with herpes and respiratory virus. We describe a child who suffered a tonic-clonic seizure with hypotension, tachycardia and low Glasgow Coma Scale. She maintained an altered mental status and required hemodynamic stabilization in the Pediatric Intensive Care Unit. Wide spectrum antibiotherapy was initiated. She suffered large and foul-smelling liquid not bloody stools which were cultured and studied by polymerase chain reaction. The cerebrospinal fluid was normal. Later the polymerase chain reaction stools were positive to astrovirus, and the blood polymerase chain reaction was positive to Neisseria meningitidis group B. As far as we know, this is the first case of astrovirus and Neisseria meningitidis coinfection described in children. This virus should be considered as new cause of viral coinfection to discard if unexplained abdominal pain or vomits and liquid stools are observed.

La infección meningocócica tiene una elevada morbimortalidad. Las coinfecciones virales han sido descritas, fundamentalmente, por virus herpes y respiratorios. Se presenta una paciente que ingresó al Servicio de Emergencia con convulsión tónico-clónica, hipotensión, taquicardia y escala de Glasgow posterior baja. En la Unidad de Cuidados Intensivos mantuvo alteración del nivel de conciencia y requirió estabilización hemodinámica. Se inició antibioterapia de amplio espectro. La paciente mostró deposiciones líquidas malolientes, sin sangre, que fueron cultivadas y estudiadas mediante reacción en cadena de la polimerasa. El líquido cefalorraquídeo fue normal. Las deposiciones resultaron positivas para astrovirus. Se confirmó, mediante reacción en cadena de la polimerasa en sangre, la presencia de Neisseria meningitidis serogrupo B. Se presenta el primer caso pediátrico de coinfección por astrovirus y Neisseria meningitidis. Este virus debería incluirse entre las causas de coinfección para descartar en caso de clínica abdominal predominante, vómitos o deposiciones líquidas.

Adverse events following immunisation with a meningococcal serogroup B vaccine: report from post-marketing surveillance, Germany, 2013 to 2016.

Background and aimIn January 2013, a novel vaccine against Neisseria meningitidis serogroup B, the multicomponent meningococcal serogroup B vaccine (4CMenB), was approved by the European Medicines Agency. We aimed to evaluate the safety profile of this vaccine. Methods: All adverse events following immunisation (AEFI) reported from Germany since the vaccine's launch in Germany in November 2013 through December 2016 were reviewed and analysed. Results: Through December 2016, a total of 664 individual case safety reports (ICSR) notifying 1,960 AEFI were received. A majority of vaccinees for whom AEFI were reported were children 2 to 11 years of age (n = 280; 42.2%) followed by infants and toddlers aged 28 days to 23 months (n = 170; 25.6%). General disorders and administration site conditions was the System Organ Class (SOC) with the majority of AEFI (n = 977; 49.8%), followed by nervous system disorders (n = 249; 12.7%), and skin and subcutaneous tissue disorders (n = 191; 9.7%). Screening of patient records for immune-mediated and neurological diseases did not raise any safety signal in terms of an increased proportional reporting ratio (PRR). Conclusions: The safety profile described in the Summary of Product Characteristics, in general, is confirmed by data from spontaneous reporting. No safety concerns were identified.

Predicting the Susceptibility of Meningococcal Serogroup B Isolates to Bactericidal Antibodies Elicited by Bivalent rLP2086, a Novel Prophylactic Vaccine.

Bivalent rLP2086 (Trumenba), a vaccine for prevention of Neisseria meningitidis serogroup B (NmB) disease, was licensed for use in adolescents and young adults after it was demonstrated that it elicits antibodies that initiate complement-mediated killing of invasive NmB isolates in a serum bactericidal assay with human complement (hSBA). The vaccine consists of two factor H binding proteins (fHBPs) representing divergent subfamilies to ensure broad coverage. Although it is the surrogate of efficacy, an hSBA is not suitable for testing large numbers of strains in local laboratories. Previously, an association between the in vitro fHBP surface expression level and the susceptibility of NmB isolates to killing was observed. Therefore, a flow cytometric meningococcal antigen surface expression (MEASURE) assay was developed and validated by using an antibody that binds to all fHBP variants from both fHBP subfamilies and accurately quantitates the level of fHBP expressed on the cell surface of NmB isolates with mean fluorescence intensity as the readout. Two collections of invasive NmB isolates (n = 1,814, n = 109) were evaluated in the assay, with the smaller set also tested in hSBAs using individual and pooled human serum samples from young adults vaccinated with bivalent rLP2086. From these data, an analysis based on fHBP variant prevalence in the larger 1,814-isolate set showed that >91% of all meningococcal serogroup B isolates expressed sufficient levels of fHBP to be susceptible to bactericidal killing by vaccine-induced antibodies.IMPORTANCE Bivalent rLP2086 (Trumenba) vaccine, composed of two factor H binding proteins (fHBPs), was recently licensed for the prevention of N. meningitidis serogroup B (NmB) disease in individuals 10 to 25 years old in the United States. This study evaluated a large collection of NmB isolates from the United States and Europe by using a flow cytometric MEASURE assay to quantitate the surface expression of the vaccine antigen fHBP. We find that expression levels and the proportion of strains above the level associated with susceptibility in an hSBA are generally consistent across these geographic regions. Thus, the assay can be used to predict which NmB isolates are susceptible to killing in the hSBA and therefore is able to demonstrate an fHBP vaccine-induced bactericidal response. This work significantly advances our understanding of the potential for bivalent rLP2086 to provide broad coverage against diverse invasive-disease-causing NmB isolates.

Prevalence and genetic characteristics of 4CMenB and rLP2086 vaccine candidates among Neisseria meningitidis serogroup B strains, China.

OBJECTIVE: To systematically investigate the prevalence and genetic characteristics of 4CMenB and rLP2086 vaccine candidates among Neisseria meningitidis serogroup B (NmB) in China. METHODS: A total of 485 NmB strains isolated in 29 provinces of China between 1968 and 2016 were selected from the culture collection of the national reference laboratory according to the isolation year, location, and source. Multi-locus sequence typing (MLST) and porA gene sequencing were performed on all 485 study strains; PCR was used to detect the fHbp, nadA, and nhba gene of 432 strains; positive amplification products from the fHbp and nadA genes from all strains, as well as those of the nhba gene from 172 representative strains, were sequenced. RESULTS: MLST results showed that the predominant (putative) clonal complexes (CCs) of NmB isolates have changed over time in China. While strains that could not be assigned to existing (p)CCs were the biggest proportion, CC4821 was the most prevalent lineage (36.0%) since 2005. PCR and sequence analysis revealed that the 4CMenB and rLP2086 vaccine candidates were highly diverse. Respectively, 152 PorA genotypes and 83 VR2 sequences were identified with significant diversity within a single CC; the complete nadA gene was found in ten of 432 study strains; fHbp was present in most strains (422/432) with variant 2 predominating (82.9%) in both patient- and carrier- derived isolates; almost all strains harbored the nhba gene while sequences were diverse. CONCLUSIONS: With regards to clonal lineages and vaccine candidate proteins, NmB isolates from China were generally diverse. Further studies should be performed to evaluate the cross-protection of present vaccines against Chinese NmB strains.