Serotype Antigens Research Articles

The impact of human leukocyte antigen donor and recipient serotyping and matching on liver transplant graft failure in primary sclerosing cholangitis, autoimmune hepatitis, and primary biliary cholangitis.

Human leukocyte antigen (HLA) serotyping is not considered to have significant impact on liver graft survival and does not factor into U.S. organ allocation. Immune-related liver diseases such as primary sclerosing cholangitis (PSC), autoimmune hepatitis (AIH), and primary biliary cholangitis (PBC) have been speculated to represent a disease subgroup that may have significantly different graft outcomes depending on HLA donor/recipient characterization. The aim of this study was to investigate whether HLA serotyping/matching influenced post-transplant graft failure for immune-related liver diseases using the United Network for Organ Sharing database. From 1994 to 2015, 5665 patients underwent first-time liver-only transplants for PSC, AIH, and PBC with complete graft survival and donor/recipient HLA data. Graft failure was noted in 38.6% (2188/5665), and all groups had comparable 5-year graft survival (75.1%-78.8%, P=0.069). The overall degree of, and loci-specific mismatch level, did not influence outcomes. Multivariable Cox proportional hazards regression noted increased graft failure risk for recipient HLA-B7, HLA-B57, HLA-B75, HLA-DR13 and donor HLA-B55, HLA-B58, and HLA-DR8 for PSC patients, protective effects for recipient HLA-DR1 and HLA-DR3 for AIH patients, and increased risk for HLA-DR7 for AIH patients. These findings warrant further investigation to evaluate the impact of HLA serotyping on post-transplant outcomes.

Development and Utilization of VHH Antibodies Derived from Camelus Dromedarius Against Foot-and-Mouth Disease Virus

ABSTRACTFoot-and-mouth disease (FMD) is an acute, highly contagious, and economically devastating viral disease of domestic and wildlife species. For effective implementation of FMD control program, there is an imperative need for developing a rapid, sensitive, and specific diagnostics which help in the identification of serotypes involved in the outbreaks. The humoral immune response of the Camelidae is unique since in these animals 75% of circulating antibodies are constituted by heavy-chain antibodies and 25% are conventional immunoglobulin with two identical heavy chains. In the present study, we developed and characterized FMD virus-specific single-domain heavy-chain antibodies (VHHs) against inactivated whole-virus antigens of FMDV serotypes O (INDR2/1975), A (IND40/2000), and Asia 1 (IND63/1972) vaccine strains. After six rounds of panning and enrichment, these VHHs were stably expressed in Escherichia coli cells. The VHHs directed against outer capsid proteins of FMD virus were successfully utilized as the capture antibody in liquid-phase blocking ELISA (LPBE) thus replacing rabbit coating antibodies. Our study demonstrated the utility of FMD virus-specific VHHs as potential candidates in FMD research and diagnostic application.

13-Valent vaccine serotype pneumococcal community acquired pneumonia in adults in high clinical risk groups

There is debate regarding the value of vaccinating adults with the 13-valent pneumococcal conjugate vaccine (PCV-13). This analysis was conducted to investigate the risk of PCV-13 serotype community acquired pneumonia (CAP) in hospitalised adults with co-morbid disease and risk factors for pneumococcal disease in the UK.Consecutive adults hospitalised (2008–2013) with a primary diagnosis of CAP, were recruited. Pneumococcal aetiology disease was identified by use of pneumococcal urinary antigen detection and serotype identification using a validated multiplex immunoassay or serum latex agglutination. Adults with PCV-13 serotype CAP were compared to those with non-PCV-13 serotype CAP.Of 2224 patients, PCV-13 serotype CAP was identified in 337 (15.2%) and non-PCV-13 serotype CAP in 250 (11.2%) individuals. Adults aged ≥65 years with one or more clinical risk factors had a significantly lower risk of PCV-13 serotype CAP compared to those aged 16–64 years without clinical risk factors (aOR 0.61, 95%CI 0.41–0.92, p = .018). In a stacked-risk analysis, the presence of incremental clinical risk factors was associated with lower odds of PCV-13 disease (p for trend = .029) Adults with underlying chronic respiratory disease (aOR) 0.56, 95% CI 0.36–0.85, p = .007) and chronic kidney disease (aOR 0.48, 95% CI 0.25–0.92, p = .028) had significantly lower adjusted odds of PCV-13 compared to non-PCV-13 serotype CAP.This analysis suggests that in the UK, the burden of PCV13 disease is greater in adults outside the traditional ‘at-risk’ groups compared to adults in ‘at-risk’ groups.

Molecular characterization of diarrheagenic Escherichia coli pathotypes: Association of virulent genes, serogroups, and antibiotic resistance among moderate-to-severe diarrhea patients.

Diarrheagenic Escherichia coli (DEC) signifies as an important etiological agent of moderate-to-severe diarrhea. This study was primarily focused on molecular identification of DEC pathotypes; their association with serogroups and estimates of resistance profiles against different antibiotics regime. Five hundred seventy-two stool specimens from diarrhea patients were investigated for DEC pathotypes. Molecular pathotypes were identified by amplification of virulence genes associated with distinct pathotypes followed by sequencing. Diarrhea is a self-limiting disease, however, severity and persistence of infection suggest antibiotic use. Therefore, AST and MIC were determined against common antibiotic regimen. Correlations between molecular pathotypes and serogroups were analyzed by somatic "O" antigen serotyping. The present findings reveal incidence of DEC as an etiological agent up to a level of 21% among all diarrheal age groups. DEC infection rate was higher in children. Enteropathogenic E.coliEPEC, a molecular pathotype of DEC, was found as a predominant pathotype with highest frequency of 13.7%. Two other molecular pathotypes enterotoxigenic E.coli (ETEC) and enteroaggregative E.coli (EAEC) accounted for 5.7% and 1.3%, respectively for all diarrhea incidences. Serological analysis deciphered somatic antigens O26, O2, and O3 as major serogroups identified among EPEC, ETEC, and EAEC pathotypes, respectively. All DEC pathotypes exhibited high levels of antibiotic resistance except for cotrimoxazole and norfloxacin. Comprehensive molecular characterization of DEC pathotypes, their incidence estimates, and antibiogram patterns will help in ascertaining better diagnostic and therapeutic measures in management of diarrheal diseases.

Epitope-Based Vaccine Design against the Outer Membrane Glycoprotein of HCMV

Human cytomegalovirus is also known as (HCMV), a human beta-herpesvirus 5 which affects over 80% adults worldwide. HCMV infection is considered one of the most leading causes of morbidity and mortality during congenital infection. It can be lethal for the immunosuppressed, such as HIV-infected individuals and patients having their organ transplanted. Considering the clinical importance of HCMV, in this study we aim to design epitope based peptides to develop a vaccine against HCMV by targeting the envelope glycoprotein B of HCMV. We predicted total 22 epitopes and their variability were analysed. The analysis of population coverage reveals a high percentage of the coverage for the America and Europe with an overall 69.77% population coverage for the world. Finally, we predicted the 3D structure of epitope YAYIYTTYL and its binding profile with the human leukocyte antigen serotype (HLA-A*02:01 and HLA-A*02:03) were analyzed using Auto Dock Vina. Our study will facilitate the epitope-based vaccine designing of HCMV and could have a far-reaching benefit on the drug development for HCMV associated diseases.

The major histocompatibility complex class I immunopeptidome of extracellular vesicles

Extracellular vesicles (EVs) are released by most cell types and have been associated with multiple immunomodulatory functions. MHC class I molecules have crucial roles in antigen presentation and in eliciting immune responses and are known to be incorporated into EVs. However, the MHC class I immunopeptidome of EVs has not been established. Here, using a small-scale immunoisolation of the antigen serotypes HLA-A*02:01 and HLA-B*27:05 expressed on the Epstein-Barr virus-transformed B cell line Jesthom and MS of the eluted peptides from both cells and EVs, we identified 516 peptides that bind either HLA-A*02:01 or HLA-B*27:05. Of importance, the predicted serotype-binding affinities and peptide-anchor motifs did not significantly differ between the peptide pools isolated from cells or EVs, indicating that during EV biogenesis, no obvious editing of the MHC class I immunopeptidome occurs. These results, for the first time, establish EVs as a source of MHC class I peptides that can be used for the study of the immunopeptidome and in the discovery of potential neoantigens for immunotherapies.

The human RNA-binding protein and E3 ligase MEX-3C binds the MEX-3–recognition element (MRE) motif with high affinity

MEX-3 is a K-homology (KH) domain-containing RNA-binding protein first identified as a translational repressor in Caenorhabditis elegans, and its four orthologs (MEX-3A-D) in human and mouse were subsequently found to have E3 ubiquitin ligase activity mediated by a RING domain and critical for RNA degradation. Current evidence implicates human MEX-3C in many essential biological processes and suggests a strong connection with immune diseases and carcinogenesis. The highly conserved dual KH domains in MEX-3 proteins enable RNA binding and are essential for the recognition of the 3'-UTR and post-transcriptional regulation of MEX-3 target transcripts. However, the molecular mechanisms of translational repression and the consensus RNA sequence recognized by the MEX-3C KH domain are unknown. Here, using X-ray crystallography and isothermal titration calorimetry, we investigated the RNA-binding activity and selectivity of human MEX-3C dual KH domains. Our high-resolution crystal structures of individual KH domains complexed with a noncanonical U-rich and a GA-rich RNA sequence revealed that the KH1/2 domains of human MEX-3C bound MRE10, a 10-mer RNA (5'-CAGAGUUUAG-3') consisting of an eight-nucleotide MEX-3-recognition element (MRE) motif, with high affinity. Of note, we also identified a consensus RNA motif recognized by human MEX-3C. The potential RNA-binding sites in the 3'-UTR of the human leukocyte antigen serotype (HLA-A2) mRNA were mapped with this RNA-binding motif and further confirmed by fluorescence polarization. The binding motif identified here will provide valuable information for future investigations of the functional pathways controlled by human MEX-3C and for predicting potential mRNAs regulated by this enzyme.

Rhinovirus - From bench to bedside.

Rhinovirus has been neglected in the past because it was generally perceived as a respiratory virus only capable of causing mild common cold. Contemporary epidemiological studies using molecular assays have shown that rhinovirus is frequently detected in adult and pediatric patients with upper or lower respiratory tract infections. Severe pulmonary and extrapulmonary complications are increasingly recognized. Contrary to popular belief, some rhinoviruses can actually replicate well at 37°C and infect the lower airway in humans. The increasing availability of multiplex PCR panels allows rapid detection of rhinovirus and provides the opportunity for timely treatment and early recognition of outbreaks. Recent advances in the understanding of host factors for viral attachment and replication, and the host immunological response in both asthmatic and non-asthmatic individuals, have provided important insights into rhinovirus infection which are crucial in the development of antiviral treatment. The identification of novel drugs has been accelerated by repurposing clinically-approved drugs. As humoral antibodies induced by past exposure and vaccine antigen of a particular serotype cannot provide full coverage for all rhinovirus serotypes, novel vaccination strategies are required for inducing protective response against all rhinoviruses.

Dengue virus exposure among blood donors in Ghana

Dengue is an urban arbovirus whose aetiologic agent is the flavivirus with four distinct antigen serotypes (DENV-1, DENV-2, DENV-3 and DENV-4) that is transmitted to humans through the bite of the mosquito Aedes aegypti. Ghana is endemic for Aedes aegypti mosquitoes and probably dengue viruses. Due to limited data on dengue virus exposure among Ghanaians, we surveyed 188 healthy adult blood donors for the presence of IgG and IgM antibodies to the four serotypes of dengue. Five milliliters of peripheral blood from the blood donors were collected in plain tubes. Serum was then obtained and ELISA tests were employed to detect both dengue virus total antibodies and IgM. The samples were further tested for dengue virus RNA using RT-PCR. Dengue virus IgG was positive for 43.6% of all the 188 blood donor samples tested but all donors were negative for anti-dengue IgM antibody and dengue virus RNA. The rate of dengue virus total antibody exposure did not differ statistically between urban and rural districts. This study shows for the first time that some regions of Ghana are hyperendemic for dengue virus infection but suggests blood for transfusion is invariably dengue virus free. This report has provided a baseline data that will inform wider discussions about the impact of this dengue fever and also guide policy makers to develop effective and affordable early warning and outbreak response systems for Ghana.Journal of Medical and Biomedical Sciences (2016) 5(2), 30-35

Purification of 146s Antigen of Foot-and-Mouth Disease (FMD) Virus Serotypes Aby Using the Sucrose Gradient Procedure

Background: Foot-and-Mouth disease (FMD) is an acute and contagious disease in domestic ruminants, which is currently the most economical viral disease that threatens the livestock industry. The virus that causes disease belongs to the Aphthovirus genus from the family of picornaviridae. This family contains seven serotypes and is about 30 nanometers in diameter and has no external membrane, similar to other picornaviruses. Objectives: In this study, we aimed to introduce the sucrose gradient procedure as a convenient method for purification of 146s antigens. Methods: Sucrose gradient procedure (20% - 50%) was used for purification of 146s antigen of foot-and-mouth disease virus serotypes A. Then, preparation steps of the virus including concentration by polyethylene glycol, degreasing using trichloroethy- lene, centrifugation (30000 g for three hours) and washing the pellet using Tris (0.05 M) were performed. Spectrophotometer and nano-drop were used to measure the amount of the purified protein and purity evaluation, respectively. Moreover, dot blot assay was used for the confirmation of 146s antigen. Results: The pellet of the 146s antigen of FMD virus serotype A was developed at a concentration of sucrose 50%. Absorbance rate of the Foot-and-Mouth Disease virus serotypes A at wavelengths of 240, 259 and 280 nm was 1.238, 1.573 and 1.157, respectively. Moreover, the amount of 146s antigen at the same wavelengths was 163.416, 207.636 and 152.724 g/mL, respectively. The amount of purified protein by nanodrop (ND-1000, the United States) was 0.275 mg/mL. The 146s antigen was observed with 26, 29 and 64 KDa by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) and was confirmed by the dot blot assay. Conclusions: The results exhibited that sucrose gradient procedure is a good method for purification of virus.

Multiple Drug Resistance in Typhoid Fever: A Case Report

A 20-years-old girl was examined in hospital premises having the symptoms like fever, abdominal cramps, diarrhea and fatigue since last week. Palpation revealed discomfort in left upper and lower abdomen. Ultrasonography revealed hepatomegaly and increased spleen size. Hematological tests revealed anemia and typhoid test was positive for IgG. The Widal test showed that patient serum was agglutinated with lipolysacharide and flagellarproteins. The antigen of serotype S.typhi was also present. Patient was diagnosed with typhoid fever. First-line therapy was penicillin that remained uneffective. Second line therapy given was quinolones; that also remained uneffective. Antibiotic susceptibility test showed that strains were resistant to multiple drugs like chloramphenicol, ciprofloxacin and co-trimoxazole. Finally, rational therapy was third generation cephalosporin i.e. ceftriaxone. After one-week of therapy, patient physical symptoms disappear and no relapse occurred during follow up.

English

A quality foot and mouth disease (FMD) vaccine is a prerequisite for effective control in addition to other zoosanitary measures and effective biosecurity practices in disease endemic sub-Saharan countries like Nigeria. To ensure an effective control programme by vaccination, countries that practice mass vaccination campaigns need to conduct vaccine matching studies to establish a relationship between prevalent field isolates with available vaccine for effective control. To this effect, a research was conducted in order to select foot-and-mouth disease viruses (FMDV) that will give a quality vaccine containing relevant serotypes and matching strains as a pre-requisite for effective vaccine. The study was conducted using two dimensional virus neutralization assays to determine the antigenic relationship ‘r’ value between the candidate vaccine strains and the field isolates. A total of forty-two specimens (epithelial tissue) were send to the World Reference Laboratory for Foot-and-Mouth Disease (WRLFMD) for virus detection and antigen serotyping and some of the field isolates were selected for vaccine matching based on geographic location and topotypes/subtype. The isolates selected were two each of serotype O, A and SAT 2 from bovine species. The selected field isolates revealed high antigenic similarity with the vaccine strains tested showing ‘r’ value greater than 0.3 which suggests a close relationship between field isolates and vaccine strain tested. A potent vaccine containing the vaccine strain is likely to confer protection in vaccinated candidates. A vaccine match with ‘r’ value less than 0.3 suggests poor protection against challenge with the isolates. The result of this study has indicated that the selected field isolates could be used as vaccine strains for a candidate trivalent FMD vaccine production in Nigeria. Key words: foot and mouth disease (FMD) virus, ‘r’ value, vaccine strain, Nigeria.

Characterization of IgA1 protease as a surface protective antigen of Streptococcus suis serotype 2

IgA1 protease of Streptococcus suis serotype 2 (SS2) has been proven to be relative with virulence and immunogenicity, however, its protective efficacy remained to be evaluated. The present study found evidence that immunization with purified recombinant IgA1 protease (600-1926aa) could induce high IgG antibody titers and could confer complete protection against a challenge with a lethal dose of SS2 in a mouse model. In addition, our findings confirmed that the IgA1 protease distributes on the surface of SS2. Therefore, the present study identified the virulence-associated protein, IgA1 protease, as a novel surface protective antigen of SS2.

Laboratory characterization of invasive Haemophilus influenzae isolates from Nunavut, Canada, 2000–2012

BackgroundWith invasive Haemophilus influenzae serotype b (Hib) disease controlled by vaccination with conjugate Hib vaccines, there is concern that invasive disease due to non-serotype b strains may emerge.ObjectiveThis study characterized invasive H. influenzae (Hi) isolates from Nunavut, Canada, in the post-Hib vaccine era.MethodsInvasive H. influenzae isolates were identified by conventional methods at local hospitals; and further characterized at the provincial and federal public health laboratories, including detection of serotype antigens and genes, multi-locus sequence typing and antibiotic susceptibility.ResultsOf the 89 invasive H. influenzae cases identified from 2000 to 2012, 71 case isolates were available for study. There were 43 serotype a (Hia), 12 Hib, 2 Hic, 1 Hid, 1 Hie, 2 Hif and 10 were non-typeable (NT). All 43 Hia were biotype II, sequence type (ST)-23. Three related STs were found among the Hib isolates: ST-95 (n=9), ST-635 (n=2) and ST-44 (n=1). Both Hif belonged to ST-124 and the 2 Hic were typed as ST-9. The remaining Hid (ST-1288) and Hie (ST-18) belonged to 2 separate clones. Of the 10 NT strains, 3 were typed as ST-23 and the remaining 7 isolates each belonged to a unique ST. Eight Hib and 1 NT-Hi were found to be resistant to ampicillin due to β-lactamase production. No resistance to other antibiotics was detected.ConclusionDuring the period of 2000–2012, Hia was the predominant serotype causing invasive disease in Nunavut. This presents a public health concern due to an emerging clone of Hia as a cause of invasive H. influenzae disease and the lack of published guidelines for the prophylaxis of contacts. The clonal nature of Hia could be the result of spread within an isolated population, and/or unique characteristics of this strain to cause invasive disease. Further study of Hia in other populations may provide important information on this emerging pathogen. No antibiotic resistance was detected among Hia isolates; a small proportion of Hib and NT-Hi isolates demonstrated resistance to ampicillin due to β-lactamase production.

Serotyping reanalysis of unserotypable Actinobacillus pleuropneumoniae isolates by agar gel diffusion test.

We observed increasing unserotypable (UT) Actinobacillus pleuropneumoniae isolates using agar gel diffusion (AGD) test. To reanalyze their serovar, we performed rapid slide agglutination (RSA) test and multiplex PCR for 47 UT isolates. Of these, 25 were serovar 1 (UT-serovar 1), 20 were serovar 2 (UT-serovar 2) and 2 were serovar 15 (UT-serovar 15). We examined serotyping antigen extraction temperature to determine heat influence. UT-serovar 1 and 15 were influenced by heat, because their precipitation lines were observed in the case of low antigen extraction temperature. To investigate the relationship between antigenicity and genotype, we performed pulsed-field gel electrophoresis (PFGE) analysis using UT-serovar 2 and 15. The predominant PFGE pattern of UT-serovar 2 was identical to that of serovar 2.

Polymorphisms in HLA Class II Genes Are Associated With Susceptibility to Staphylococcus aureus Infection in a White Population.

Staphylococcus aureus can cause life-threatening infections. Human susceptibility to S. aureus infection may be influenced by host genetic variation. A genome-wide association study (GWAS) in a large health plan-based cohort included biologic specimens from 4701 culture-confirmed S. aureus cases and 45 344 matched controls; 584 535 single-nucleotide polymorphisms (SNPs) were genotyped on an array specific to individuals of European ancestry. Coverage was increased by imputation of >25 million common SNPs, using the 1000 Genomes Reference panel. In addition, human leukocyte antigen (HLA) serotypes were also imputed. Logistic regression analysis, performed under the assumption of an additive genetic model, revealed several imputed SNPs (eg, rs115231074: odds ratio [OR], 1.22 [P = 1.3 × 10(-10)]; rs35079132: OR, 1.24 [P = 3.8 × 10(-8)]) achieving genome-wide significance on chromosome 6 in the HLA class II region. One adjacent genotyped SNP was nearly genome-wide significant (rs4321864: OR, 1.13; P = 8.8 × 10(-8)). These polymorphisms are located near the genes encoding HLA-DRA and HLA-DRB1. Results of further logistic regression analysis, in which the most significant GWAS SNPs were conditioned on HLA-DRB1*04 serotype, showed additional support for the strength of association between HLA class II genetic variants and S. aureus infection. Our study results are the first reported evidence of human genetic susceptibility to S. aureus infection.

Development and Evaluation of a Rapid Antigen Detection and Serotyping Lateral Flow Antigen Detection System for Foot-and-Mouth Disease Virus.

We developed a lateral flow strip using monoclonal antibodies (MAbs) which allows for rapid antigen detection and serotyping of foot-and-mouth disease virus (FMDV). This FMDV serotyping strip was able to detect all 7 serotypes and distinguish serotypes O, A, C and Asia1. Its sensitivities ranged from 103 to 104 of a 50% tissue culture infectious dose of each FMDV stain; this is equal to those of the commercial product Svanodip (Boehringer Ingelheim Svanova, Uppsala, Sweden), which can detect all seven serotypes of FMDV, but does not distinguish them. Our evaluation of the FMDV serotyping strip using a total of 118 clinical samples (vesicular fluids, vesicular epithelial emulsions and oral and/or nasal swabs) showed highly sensitive antigen detection and accuracy in serotyping in accordance with ELISA or RT-PCR. To the best of our knowledge, this is the first report on any FMDV serotyping strip that provides both rapid antigen detection and serotyping of FMDV at the same time on one strip without extra devices. This method will be useful in both FMD-free countries and FMD-infected countries, especially where laboratory diagnosis cannot be carried out.

Characterization of invasive Neisseria meningitidis strains from Québec, Canada, during a period of increased serogroup B disease, 2009-2013: phenotyping and genotyping with special emphasis on the non-carbohydrate protein vaccine targets.

BackgroundThe epidemiology of invasive meningococcal disease (IMD) in Québec, Canada, has been dominated in the past decade by a clone of serogroup B (MenB) Neisseria meningitidis defined by multi-locus sequence typing (MLST) as sequence type (ST)-269. With the licensure of a new MenB vaccine Bexsero (4CMenB) in Canada, this study characterized invasive N. meningitidis recovered in Québec from 2009 to 2013, with an objective to examine the diversity of the 4CMenB vaccine antigens. Isolates were serogrouped by antisera and genogrouped by PCR, and further typed by whole cell ELISA for serotype and serosubtype antigens. Clonal analysis was done by MLST. Isolates were genotyped by analysis of their 4CMenB vaccine antigen genes of PorA, factor H binding protein (fHbp), Neisserial Heparin Binding Antigen (NHBA), and Neisseria Adhesin A (NadA).ResultsOf the 263 IMD isolates analysed, 229, 16, 10, 7, and 1 belonged to MenB, MenY, MenW, MenC, and MenX, respectively. Of the 229 MenB, 159 (69.4 %) were typed as ST-269 clonal complex (CC); and they possessed a restricted number of three fHbp and five nhba gene alleles. Nine N. meningitidis isolates (eight MenB and one MenY) were found to possess at least one gene that encoded for an antigen that matched exactly with protein variants in the 4CMenB vaccine. Two MenB expressed PorA antigen P1.4 and possessed the nhba gene for peptide 2; four other MenB were predicted to have NHBA peptide 2; another two MenB were predicted to encode fHbp peptide 1.1; and a single MenY was found to have nadA gene for NadA peptide 8. In addition, another 172 isolates were found to possess genes for variant 1 fHbp peptides other than peptide 1.1 or NadA variant 1-2/3 peptides other than peptide 8; and therefore, may potentially be covered by 4CMenB.ConclusionThe most prevalent clone of N. meningitidis in Quebec was ST-269 CC; and 96 % of the isolates in this CC were predicted to be covered by 4CMenB vaccine. Extensive genetic diversity was found in the other IMD isolates in Québec which might suggest a lower coverage by the vaccine when compared to the ST-269 MenB.Electronic supplementary materialThe online version of this article (doi:10.1186/s12866-015-0469-6) contains supplementary material, which is available to authorized users.

Genetic and antigenic characterization of Canadian invasive Neisseria meningitidis serogroup C (MenC) case isolates in the post-MenC conjugate vaccine era, 2009–2013

We previously reported a shift in the electrophoretic type (ET) of invasive MenC in Canada from predominantly ET-15 to ET-37 in the post-MenC conjugate vaccine period. This study sought to confirm this trend by examining all culture-confirmed invasive MenC case isolates in Canada in the period from 1 January 2009 to 31 December 2013. Of the 50 MenC isolates, 18 belonged to ET-15, 28 belonged to ET-37 (but not ET-15), and four belonged to other clonal types. Analysis of the serotype and serosubtype antigens, porA and fetA gene sequences provided data to show that invasive MenC belonging to ET-15 and ET-37 were two very different subpopulations within the ST-11 clonal complex. Sequence analysis of the fHbp genes suggested that 12 different types of factor H-binding protein were found among the ET-15 isolates while 86 % of ET-37 isolates were found to have fHbp genes predicted to encode peptide 22. The nadA gene in 12 MenC isolates was disrupted due to IS1301 insertion and 11 of these 12 isolates belonged to ET-15. Ten per cent of the invasive MenC were found to have a frame-shift mutation in their fHbp genes that predicted no fHbp produced. Significant diversity and frame-shift mutations of fHbp genes were found in invasive MenC strains in Canada.

Genetic and antigenic characterization of Canadian invasive Neisseria meningitidis serogroup C (MenC) case isolates in the post-MenC conjugate vaccine era, 2009-2013.

We previously reported a shift in the electrophoretic type (ET) of invasive MenC in Canada from predominantly ET-15 to ET-37 in the post-MenC conjugate vaccine period. This study sought to confirm this trend by examining all culture-confirmed invasive MenC case isolates in Canada in the period from 1 January 2009 to 31 December 2013. Of the 50 MenC isolates, 18 belonged to ET-15, 28 belonged to ET-37 (but not ET-15), and four belonged to other clonal types. Analysis of the serotype and serosubtype antigens, porA and fetA gene sequences provided data to show that invasive MenC belonging to ET-15 and ET-37 were two very different subpopulations within the ST-11 clonal complex. Sequence analysis of the fHbp genes suggested that 12 different types of factor H-binding protein were found among the ET-15 isolates while 86 % of ET-37 isolates were found to have fHbp genes predicted to encode peptide 22. The nadA gene in 12 MenC isolates was disrupted due to IS1301 insertion and 11 of these 12 isolates belonged to ET-15. Ten per cent of the invasive MenC were found to have a frame-shift mutation in their fHbp genes that predicted no fHbp produced. Significant diversity and frame-shift mutations of fHbp genes were found in invasive MenC strains in Canada.