Publications by authors named "Laura Serino"

45 Publications

Endogenous complement human serum bactericidal assay (enc-hSBA) for vaccine effectiveness assessments against meningococcal serogroup B.

NPJ Vaccines 2021 Feb 23;6(1):29. Epub 2021 Feb 23.

GSK, Rixensart, Belgium.

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.
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http://dx.doi.org/10.1038/s41541-021-00286-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7902841PMC
February 2021

Cross-reactivity of 4CMenB vaccine-induced antibodies against meningococci belonging to non-B serogroups in Italy.

Hum Vaccin Immunother 2021 Jan 31:1-7. Epub 2021 Jan 31.

Department Infectious Diseases, Istituto Superiore di Sanità , Rome, Italy.

The four-component meningococcal serogroup B vaccine (4CMenB) contains antigens present in the majority of meningococci causing invasive meningococcal disease (IMD) and may potentially offer protection against strains belonging to non-B serogroups. This study aimed to evaluate the ability of 4CMenB-induced antibodies to kill, in a human serum bactericidal assay (hSBA), non-B meningococci belonging to the main genotypes responsible for IMD in Italy. Meningococci, collected between 2015 and 2017, was characterized for PorA, FetA and sequence type, and for clonal complex. Twenty non-B isolates, representative of the most frequent genotypes, were molecularly characterized for 4CMenB antigens and tested in hSBA with sera from 4CMenB-vaccinated infants and adolescents. Among twenty isolates, eleven were serogroup C, five were Y, two W and two X. All isolates contained genes encoding for fHbp and NHBA antigens and four harbored the NadA full-length encoding gene. Positive hSBA titers were obtained against all serogroup W, X and Y isolates and against five serogroup C isolates. These data show that the 4CMenB vaccine can induce bactericidal antibodies against genetically representative meningococcal W, Y and X strains from Italy. For serogroup C, different susceptibilities to killing were observed for strains with similar antigenic repertoires.
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http://dx.doi.org/10.1080/21645515.2020.1855951DOI Listing
January 2021

Genomic Characterization of Invasive Meningococcal Serogroup B Isolates and Estimation of 4CMenB Vaccine Coverage in Finland.

mSphere 2020 09 16;5(5). Epub 2020 Sep 16.

GSK, Siena, Italy

Invasive meningococcal disease (IMD) caused by is a significant cause of morbidity and mortality worldwide. In Finland, the incidence rate of IMD is low, with meningococcal serogroup B (MenB) accounting for around one-third of IMD cases annually. The aim of this study was to investigate the genetic variability of invasive MenB isolates collected in Finland between 2010 and 2017 ( = 81), including the genes encoding the 4-component MenB vaccine (4CMenB; Bexsero; GSK) antigens and their promoters, and to evaluate the 4CMenB potential coverage. Whole-genome sequencing was performed. The meningococcal antigen typing system (MATS) was used to characterize MenB isolates and predict the potential coverage of 4CMenB. MATS was complemented by genetic MATS (gMATS) through association of antigen genotyping and phenotypic MATS results. Multilocus sequence typing revealed predominance of the ST-41/44 clonal complex among which sequence type (ST)-303 was the most common and was predicted to be covered by 4CMenB. Of the 4 major vaccine antigens, the factor H-binding protein variant 1, neisserial heparin binding antigen peptide 2, and the PorA P1.4 antigen were predominant, whereas adhesin A was present in only 4% of the 81 isolates. MATS and gMATS 4CMenB strain coverage predictions were 78% and 86%, respectively, in a subpanel of 60 isolates collected during 2010 to 2014, with a gMATS prediction of 84% for all 81 isolates. The results suggest that 4CMenB could reduce the burden of IMD in Finland and that gMATS could be applied to monitor vaccine strain coverage and predict vaccine effectiveness. 4CMenB is a 4-component vaccine used against invasive meningococcal disease (IMD) caused by serogroup B (MenB). We investigated the genetic variability of MenB in Finland and evaluated 4CMenB strain coverage by 2 different methods: MATS (meningococcal antigen typing system) and gMATS (genetic MATS). In a set of MenB isolates, 78% (MATS) and 86% (gMATS) were predicted as covered by 4CMenB, suggesting that use of 4CMenB would help reduce IMD incidence in Finland. MATS has been used in 13 countries worldwide, generating information on phenotypic characteristics that could infer protection by 4CMenB. Based on these data and genetic information, gMATS coverage predictions can be made. gMATS predicts coverage consistent with MATS for about 94% of tested strains. Unlike MATS, gMATS does not require live isolates, thus allowing the analysis also of noncultivable strains, making the coverage predictions more accurate. Therefore, gMATS can replace MATS to assess 4CMenB coverage, including in regions with no prior MATS data.
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http://dx.doi.org/10.1128/mSphere.00376-20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7494829PMC
September 2020

Healthcare Workers Training Courses on Vaccinations: A Flexible Format Easily Adaptable to Different Healthcare Settings.

Vaccines (Basel) 2020 Sep 8;8(3). Epub 2020 Sep 8.

Department of Biomedicine and Prevention, University of Rome Tor Vergata, 00133 Rome, Italy.

Since 2017, Italy has expanded the compulsory vaccination from 4 to 10 for those aged 0 to 16 years. Because of the great organizational effort required for the immunization services, minor attention was given to the vaccinations not included among the mandatory ones. This situation led to a real difficulty in harmonizing the vaccination procedures even inside a single region. In the Lazio region, the Laboratory of Vaccinology of the University of Rome Tor Vergata established a working group to create a new training model for healthcare professionals. The course program proposed an update of three vaccinations which are not mandatory but actively offered. It included the same part of scientific updating and a variable part based on local experiences. A specific anonymous questionnaire on knowledge and attitude was administered. The study aimed to propose a general format of training courses for vaccination centers adaptable to the individual local health units (ASLs) and to evaluate through questionnaires. The results show differences in knowledge and attitudes toward non-mandatory vaccinations among the ASLs of Lazio, confirming the usefulness of a support to make knowledge and procedures homogeneous. This model could be adapted to any healthcare setting and exported to other services.
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http://dx.doi.org/10.3390/vaccines8030514DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7563464PMC
September 2020

The global meningitis genome partnership.

J Infect 2020 10 29;81(4):510-520. Epub 2020 Jun 29.

Meningitis Research Foundation, Newminster House, 27-29 Newminster House, Baldwin Street, Bristol BS1 1LT, UK.

Genomic surveillance of bacterial meningitis pathogens is essential for effective disease control globally, enabling identification of emerging and expanding strains and consequent public health interventions. While there has been a rise in the use of whole genome sequencing, this has been driven predominately by a subset of countries with adequate capacity and resources. Global capacity to participate in surveillance needs to be expanded, particularly in low and middle-income countries with high disease burdens. In light of this, the WHO-led collaboration, Defeating Meningitis by 2030 Global Roadmap, has called for the establishment of a Global Meningitis Genome Partnership that links resources for: N. meningitidis (Nm), S. pneumoniae (Sp), H. influenzae (Hi) and S. agalactiae (Sa) to improve worldwide co-ordination of strain identification and tracking. Existing platforms containing relevant genomes include: PubMLST: Nm (31,622), Sp (15,132), Hi (1935), Sa (9026); The Wellcome Sanger Institute: Nm (13,711), Sp (> 24,000), Sa (6200), Hi (1738); and BMGAP: Nm (8785), Hi (2030). A steering group is being established to coordinate the initiative and encourage high-quality data curation. Next steps include: developing guidelines on open-access sharing of genomic data; defining a core set of metadata; and facilitating development of user-friendly interfaces that represent publicly available data.
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http://dx.doi.org/10.1016/j.jinf.2020.06.064DOI Listing
October 2020

Culture-Confirmed Invasive Meningococcal Disease in Canada, 2010 to 2014: Characterization of Serogroup B Strains and Their Predicted Coverage by the 4CMenB Vaccine.

mSphere 2020 03 4;5(2). Epub 2020 Mar 4.

GSK, Siena, Italy.

The molecular epidemiology of culture-confirmed invasive meningococcal disease (IMD) in Canada from 2010 to 2014 was studied with an emphasis on serogroup B (MenB) isolates, including their predicted coverage by the 4CMenB vaccine. The mean annual incidence rates of culture confirmed IMD varied from 0.19/100,000 in Ontario to 0.50/100,000 in New Brunswick and 0.59/100,000 in Quebec. In both Quebec and Atlantic region, MenB was significantly more common than other serogroups, while in other provinces, both MenB and serogroup Y (MenY) were almost equally common. The majority of MenB cases (67.0%) were in those aged ≤24 years, while most MenC (75.0%) and MenY (69.6%) cases were in adults more than 24 years old. The 349 MenB isolates were grouped into 103 sequence types (STs), 90 of which belonged to 13 clonal complexes (CCs). A large number of 4CMenB antigen genes were found among the Canadian MenB, which is predicted to encode 50 factor H binding protein (fHbp) types, 40 NHBA types, and 55 PorA genotypes. Provinces and regions were found to have their own unique MenB STs. A meningococcal antigen typing system assay predicted an overall MenB coverage by 4CMenB to be 73.6%, with higher coverage predicted for the two most common STs: 100% for ST154 and 95.9% for ST269, leading to higher coverage in both the Atlantic region and Quebec. Higher coverage (81.4%) was also found for MenB recovered from persons aged 15 to 24 years, followed by strains from infants and children ≤4 years old (75.2%) and those aged 5 to 14 years (75.0%). Laboratory surveillance of invasive meningococcal disease (IMD) is important to our understanding of the evolving nature of the strain types causing the disease and the potential coverage of disease strains by the newly developed vaccines. This study examined the molecular epidemiology of culture-confirmed IMD cases in Canada by examining the strain types and the potential coverage of a newly licensed 4CMenB vaccine on Canadian serogroup B strains. The strain types identified in different parts of Canada appeared to be unique as well as their predicted coverage by the 4CMenB vaccine. These data were compared to data obtained from previous studies done in Canada and elsewhere globally. For effective control of IMD, laboratory surveillance of this type was found to be essential and useful to understand the dynamic nature of this disease.
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http://dx.doi.org/10.1128/mSphere.00883-19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7056808PMC
March 2020

[Adverse reactions after repeated doses of anti-tetanus vaccine: scientific evidences].

Ig Sanita Pubbl 2019 Jul-Aug;75(4):317-325

Dipartimento di Biomedicina e Prevenzione, Tor Vergata Università degli Studi di Roma, Italia.

The possible risk of hyperimmunization after tetanus vaccination is currently discussed after the National Vaccine Prevention Plan 2017-2019 confirmed the recommendation of a booster dose every ten years. Due to the ubiquitous nature of tetanus spores and the inability to obtain herd-immunity through vaccination, efforts to reduce the incidence of tetanus aim at eliminating the disease. The only way to prevent infection is vaccination followed by recommended periodic booster doses. Between 2012 and 2016, Italy notified 45% (252/564) of all cases reported by the 26 EU Member States, most of them in the over 65 age group, generally women in the rural areas. The recommendation of the antipertussis vaccine, combined with anti-tetanus, in pregnancy and the indications for antitetanic prophylaxis by vaccination or specific immunoglobulins in emergency setting, gives rise to doubts about the risk of hyperimmunization. Studies generally agree on the safety of diphtheria-tetanus-pertussis combined vaccines during the third trimester of pregnancy, and the time elapsed since the previous tetanus vaccination seems not to be related to significant differences in the incidence of adverse events or obstetrical complications. In the emergency wards, given the relatively high incidence of tetanus in Italy, the risk/benefit ratio often leads to prefer vaccination to no-intervention. The administration of tetanus immunoglobulins in subjects not vaccinated in the last 10 years seems justified by the epidemiology of tetanus in Italy.
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January 2020

Does vaccination with 4CMenB convey protection against meningococcal serogroup B strains not predicted to be covered by MATS? A study of the UK clonal complex cc269.

Hum Vaccin Immunother 2020 04 6;16(4):945-948. Epub 2019 Dec 6.

GSK, Siena, Italy.

The Meningococcal Antigen Typing System (MATS) has been developed as an hSBA surrogate to evaluate potential coverage afforded by the 4-component meningococcal serogroup B vaccine (4CMenB: , GSK). We investigated whether the lower value of MATS coverage among invasive Meningococcus serogroup B clonal complex 269 strains from the United Kingdom (53% in 2014-2015 versus 73% in 2007-2008) reflected the lower bactericidal activity of the vaccine against these isolates. A total of 34 MATS-negative strains (31 were cc269 or closely related) were tested against pooled sera from 32 or 72 4CMenB-vaccinated infants in a serum bactericidal antibody assay in presence of human complement (hSBA). All infants had received four 4CMenB doses in the first 2 y of life. Baseline sera comprised 180 pooled samples from healthy-unvaccinated 2-month-old infants. Twenty of the 34 (59%) MATS-negative strains were killed in hSBA with titers ≥4 by pooled sera from vaccinated infants. There were 13/34 strains with hSBA titers ≥4 and at least a 4-fold rise in titer with respect to pooled baseline sera, and 10/34 with hSBA titers ≥8 and at least a 4-fold rise in titer with respect to baseline. These data confirm MATS as a conservative estimate for predicting strain coverage by 4CMenB.
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http://dx.doi.org/10.1080/21645515.2019.1688039DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7227617PMC
April 2020

[Anti-pneumococcus, anti-herpes-zoster and anti-papillomavirus vaccinations: experience in programming continuing education courses in local health units in Rome].

Ig Sanita Pubbl 2019 Jan-Feb;75(1):80-89

Dipartimento di Biomedicina e Prevenzione, Tor Vergata Università degli Studi di Roma, Italia.

The National Vaccine Prevention Plan considers the recommendations for immune prophylaxis in all ages of life. However, compulsory vaccination introduced in 2017 focused the attention on improving global vaccination coverage in infants and children, giving less attention to adult/elderly vaccinations. The immunization of this population is necessary considering the change in the age structure of the population, whose average life expectancy is increasing. Aim of this work was the organization of continuing education courses about anti-Pneumococcus, anti-Herpes-Zoster and anti-Papillomavirus vaccinations to offer an update of knowledge and to discuss the attitudes of health professionals in vaccination centers of the Local Health Units in Rome.
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October 2019

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

Vaccine 2019 02 17;37(7):991-1000. Epub 2019 Jan 17.

GSK, Siena, Italy. Electronic address:

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.
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http://dx.doi.org/10.1016/j.vaccine.2018.12.061DOI Listing
February 2019

Potential Coverage of the 4CMenB Vaccine against Invasive Serogroup B Isolated from 2009 to 2013 in the Republic of Ireland.

mSphere 2018 08 22;3(4). Epub 2018 Aug 22.

GSK Vaccines, Siena, Italy.

is a common cause of bacterial meningitis in children and young adults worldwide. The 4CMenB vaccine (Bexsero), developed to combat meningococcal serogroup B (MenB) disease, contains subcapsular antigens that may induce immunity against strains of , regardless of serogroup. Owing to differential levels of expression and peptide diversity in vaccine antigens across meningococcal strains, the eningococcal ntigen yping ystem (MATS) was developed to estimate the potential MenB strain coverage of 4CMenB. Prior to introducing the 4CMenB vaccine into routine use, we sought to estimate the potential 4CMenB coverage against invasive MenB strains isolated in the Republic of Ireland (RoI) over four consecutive epidemiological years. MATS was applied to a panel of 105 invasive MenB strains isolated during July 2009 to June 2013. Sequence data characterizing the multilocus sequence typing (MLST) alleles and the major 4CMenB target peptides were extracted from isolate genome sequence data, hosted in the Bacterial Isolate Sequencing database (BIGSdb). MATS data indicated that 4CMenB may induce protective immunity against 69.5% (95% confidence interval [CI], 64.8% to 84.8%) of circulating MenB strains. Estimated coverage was highest against the most prevalent disease-causing lineage, cc41/44, where the most frequently observed sequence types, ST-154 and ST-41 (21% of isolates, collectively), were typically covered by three antigens. No significant temporal trends were observed. Overall, these data provide a baseline of strain coverage prior to the introduction of 4CMenB and indicate that a decrease in invasive meningococcal disease (IMD) is predicted following the introduction of 4CMenB into the routine infant immunization schedule in the RoI. The meningococcal antigen typing system (MATS) is an enzyme-linked immunosorbent assay (ELISA) that measures both the levels of expression and the immune reactivity of the three recombinant 4CMenB antigens. Together with PorA variable-region sequence data, this system provides an estimation of how susceptible MenB isolates are to killing by 4CMenB vaccine-induced antibodies. Assays based on subcapsular antigen phenotype analyses, such as MATS, are important in situations where conventional vaccine coverage estimations are not possible. Subcapsular antigens are typically highly diverse across strains, and vaccine coverage estimations would require unfeasibly large efficacy trials and screening of an exhaustive strain panel for antibody functional activity. Here, MATS was applied to all invasive meningococcal serogroup B (MenB) strains isolated over four consecutive epidemiological years ( = 105) and predicted reasonably high 4CMenB vaccine coverage in the Republic of Ireland.
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http://dx.doi.org/10.1128/mSphere.00196-18DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6106058PMC
August 2018

Meningococcal Antigen Typing System (MATS)-Based Serogroup B Coverage Prediction for the MenB-4C Vaccine in the United States.

mSphere 2017 Nov-Dec;2(6). Epub 2017 Nov 15.

GSK, Siena, Italy.

is the most common cause of bacterial meningitis in children and young adults worldwide. A 4-component vaccine against serogroup B (MenB) disease (MenB-4C [Bexsero]; GSK) combining factor H binding protein (fHBP), neisserial heparin binding protein (NHBA), neisserial adhesin A (NadA), and PorA-containing outer membrane vesicles was recently approved for use in the United States and other countries worldwide. Because the public health impact of MenB-4C in the United States is unclear, we used the meningococcal antigen typing system (MATS) to assess the strain coverage in a panel of strains representative of serogroup B (NmB) disease in the United States. MATS data correlate with killing in the human complement serum bactericidal assay (hSBA) and predict the susceptibility of NmB strains to killing in the hSBA, the accepted correlate of protection for MenB-4C vaccine. A panel of 442 NmB United States clinical isolates (collected in 2000 to 2008) whose data were down weighted with respect to the Oregon outbreak was selected from the Active Bacterial Core Surveillance (ABCs; CDC, Atlanta, GA) laboratory. MATS results examined to determine strain coverage were linked to multilocus sequence typing and antigen sequence data. MATS predicted that 91% (95% confidence interval [CI], 72% to 96%) of the NmB strains causing disease in the United States would be covered by the MenB-4C vaccine, with the estimated coverage ranging from 88% to 97% by year with no detectable temporal trend. More than half of the covered strains could be targeted by two or more antigens. NHBA conferred coverage to 83% (CI, 45% to 93%) of the strains, followed by factor H-binding protein (fHbp), which conferred coverage to 53% (CI, 46% to 57%); PorA, which conferred coverage to 5.9%; and NadA, which conferred coverage to 2.5% (CI, 1.1% to 5.2%). Two major clonal complexes (CC32 and CC41/44) had 99% strain coverage. The most frequent MATS phenotypes (39%) were fHbp and NHBA double positives. MATS predicts over 90% MenB-4C strain coverage in the United States, and the prediction is stable in time and consistent among bacterial genotypes. The meningococcal antigen typing system (MATS) is an enzyme-linked immunosorbent assay (ELISA)-based system that assesses the levels of expression and immune reactivity of the three recombinant MenB-4C antigens and, in conjunction with PorA variable 2 (VR2) sequencing, provides an estimate of the susceptibility of NmB isolates to killing by MenB-4C-induced antibodies. MATS assays or similar antigen phenotype analyses assume importance under conditions in which analyses of vaccine coverage predictions are not feasible with existing strategies, including large efficacy trials or functional antibody screening of an exhaustive strain panel. MATS screening of a panel of NmB U.S. isolates ( = 442) predicts high MenB-4C vaccine coverage in the United States.
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http://dx.doi.org/10.1128/mSphere.00261-17DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5687916PMC
November 2017

Meningococcal serogroup B strain coverage of the multicomponent 4CMenB vaccine with corresponding regional distribution and clinical characteristics in England, Wales, and Northern Ireland, 2007-08 and 2014-15: a qualitative and quantitative assessment.

Lancet Infect Dis 2017 07 30;17(7):754-762. Epub 2017 Mar 30.

Meningococcal Reference Unit, Public Health England, Manchester, UK.

Background: The UK introduced 4CMenB-a multicomponent vaccine against serogroup B meningococcal disease-into the national infant immunisation programme in September, 2015. The Meningococcal Antigen Typing System (MATS) was used to estimate coverage by 4CMenB of invasive meningococcal group B isolates obtained during 2007-08 in England and Wales (MATS coverage). We aimed to repeat the MATS survey for invasive meningococcal group B isolates obtained during 2014-15, before 4CMenB introduction; compare strain coverage between 2007-08 and 2014-15; and investigate associations between MATS coverage, age, region, and disease outcomes.

Methods: Invasive serogroup B meningococcal isolates from cases in England, Wales, and Northern Ireland during 2014-15 were assayed using MATS and compared with 2007-08 data. MATS coverage was assessed by geographical region and age group. Clinical characteristics, risk factors, and outcomes were assessed according to MATS coverage for 2014-15 English cases.

Findings: In 2014-15, 165 of 251 (66%; 95% CI 52-80) meningococcal group B isolates were estimated by MATS to be covered by 4CMenB, compared with 391 of 535 (73%; 95% CI 57-87) in 2007-08. The proportion of MATS-positive isolates with one vaccine antigen increased from 23% (122 of 535) in 2007-08 to 31% (78 of 251) in 2014-15, whereas the proportion with more than one antigen fell from 50% (269 of 535) to 35% (87 of 251). This effect reflected changes in circulating strains, particularly ST-269 clonal complex strains. MATS coverage increased with age, varied by geographical region, and was associated with more severe disease.

Interpretation: In 2014-15, two-thirds of meningococcal group B isolates were predicted to be covered by 4CMenB. Temporal changes in MATS coverage underscore the need for continued monitoring of antigen expression and diversity, particularly in countries with 4CMenB programmes.

Funding: Public Health England, GlaxoSmithKline.
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http://dx.doi.org/10.1016/S1473-3099(17)30170-6DOI Listing
July 2017

Erratum to: Informed consent, and an ethico-legal framework for paediatric observational research and biobanking: the experience of an Italian birth cohort study.

Cell Tissue Bank 2016 Sep;17(3):541

Genetic Epidemiology Unit, National Centre of Epidemiology, Surveillance and Health Promotion, Istituto Superiore di Sanità, Viale Regina Elena, 299, 00161, Rome, Italy.

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http://dx.doi.org/10.1007/s10561-016-9552-yDOI Listing
September 2016

Pathogenic E. coli exploits SslE mucinase activity to translocate through the mucosal barrier and get access to host cells.

PLoS One 2015 19;10(3):e0117486. Epub 2015 Mar 19.

Novartis Vaccines and Diagnostics S.r.l., Via Fiorentina 1, Siena, Italy.

SslE is a zinc-metalloprotease involved in the degradation of mucin substrates and recently proposed as a potential vaccine candidate against pathogenic E. coli. In this paper, by exploiting a human in vitro model of mucus-secreting cells, we demonstrated that bacteria expressing SslE have a metabolic benefit which results in an increased growth rate postulating the importance of this antigen in enhancing E. coli fitness. We also observed that SslE expression facilitates E. coli penetration of the mucus favouring bacteria adhesion to host cells. Moreover, we found that SslE-mediated opening of the mucosae contributed to the activation of pro-inflammatory events. Indeed, intestinal cells infected with SslE-secreting bacteria showed an increased production of IL-8 contributing to neutrophil recruitment. The results presented in this paper conclusively designate SslE as an important colonization factor favouring E. coli access to both metabolic substrates and target cells.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0117486PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4366376PMC
April 2016

SslE elicits functional antibodies that impair in vitro mucinase activity and in vivo colonization by both intestinal and extraintestinal Escherichia coli strains.

PLoS Pathog 2014 May 8;10(5):e1004124. Epub 2014 May 8.

Novartis Vaccines and Diagnostics Srl, Siena, Italy.

SslE, the Secreted and surface-associated lipoprotein from Escherichia coli, has recently been associated to the M60-like extracellular zinc-metalloprotease sub-family which is implicated in glycan recognition and processing. SslE can be divided into two main variants and we recently proposed it as a potential vaccine candidate. By applying a number of in vitro bioassays and comparing wild type, knockout mutant and complemented strains, we have now demonstrated that SslE specifically contributes to degradation of mucin substrates, typically present in the intestine and bladder. Mutation of the zinc metallopeptidase motif of SslE dramatically impaired E. coli mucinase activity, confirming the specificity of the phenotype observed. Moreover, antibodies raised against variant I SslE, cloned from strain IHE3034 (SslEIHE3034), are able to inhibit translocation of E. coli strains expressing different variants through a mucin-based matrix, suggesting that SslE induces cross-reactive functional antibodies that affect the metallopeptidase activity. To test this hypothesis, we used well-established animal models and demonstrated that immunization with SslEIHE3034 significantly reduced gut, kidney and spleen colonization by strains producing variant II SslE and belonging to different pathotypes. Taken together, these data strongly support the importance of SslE in E. coli colonization of mucosal surfaces and reinforce the use of this antigen as a component of a broadly protective vaccine against pathogenic E. coli species.
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http://dx.doi.org/10.1371/journal.ppat.1004124DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4014459PMC
May 2014

Informed consent, and an ethico-legal framework for paediatric observational research and biobanking: the experience of an Italian birth cohort study.

Cell Tissue Bank 2014 Dec 5;15(4):579-90. Epub 2014 Mar 5.

Genetic Epidemiology Unit, National Centre of Epidemiology, Surveillance and Health Promotion, Istituto Superiore di Sanità, Viale Regina Elena, 299, 00161, Rome, Italy,

Birth cohort studies are important tools for life-course epidemiology, given the spectrum of the environmental, behavioural, and genetic factors that should be considered when making judgements on human health. Biobanks are valuable components of studies designed to investigate the genetic variability of diseases and improve phenotypic characterisation. In studies involving vulnerable populations and biobanks, it is essential to provide ethical reasoning and analyse the legal requirements. We describe the processes and the tools used in the iterative design of an appropriate informed consent model and the ethico-legal framework of the Piccolipiù study. The Piccolipiù study is a prospective population-based study funded by the Italian Ministry of Health that intends to enrol 3,000 newborns and their mothers in five Italian cities, and to store biological samples for future use. To realise these objectives, we performed a thorough evaluation of the literature, of national and international guidelines, and of the impact of the Italian legal requirements for research biobanking. Discussions among stakeholders facilitated the design of the informed consent and the ethico-legal framework. Several topics are addressed, including the suitability of a broad informed consent for paediatric biobanks, infant vulnerability, access to and sharing of data, and the disclosure of individual's genetic results. Discussion of the ethical and legal procedures adopted in epidemiological biobanking might be a fruitful ground for comparison both at the national level, where standardization and homogeneity are lacking, and at the international level, where different regulatory issues are often in the background and might hamper research biobanks networking.
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http://dx.doi.org/10.1007/s10561-014-9431-3DOI Listing
December 2014

Piccolipiù, a multicenter birth cohort in Italy: protocol of the study.

BMC Pediatr 2014 Feb 7;14:36. Epub 2014 Feb 7.

Background: The fetal and infant life are periods of rapid development, characterized by high susceptibility to exposures. Birth cohorts provide unique opportunities to study early-life exposures in association with child development and health, as well as, with longer follow-up, the early life origin of adult diseases. Piccolipiù is an Italian birth cohort recently set up to investigate the effects of environmental exposures, parental conditions and social factors acting during pre-natal and early post-natal life on infant and child health and development. We describe here its main characteristics.

Methods/design: Piccolipiù is a prospective cohort of expected 3000 newborns, who will be recruiting in six maternity units of five Italian cities (Florence, Rome, Trieste, Turin and Viareggio) since October 2011. Mothers are contacted during pregnancy or at delivery and are offered to participate in the study. Upon acceptance, their newborns are recruited at birth and followed up until at least 18 years of age. At recruitment, the mothers donate a blood sample and complete a baseline questionnaire. Umbilical cord blood, pieces of umbilical cord and heel blood spots are also collected. Postnatal follow-up currently occurs at 6, 12, and 24 months of age using on-line or postal self administered questionnaire; further questionnaires and medical examinations are envisaged. Questionnaires collect information on several factors, including mother's and/or child's environmental exposures, anthropometric measures, reproductive factors, diet, supplements, medical history, cognitive development, mental health and socioeconomic factors. Health promotion materials are also offered to parents.

Discussion: Piccolipiù will broaden our understanding of the contribution of early-life factors to infant and child health and development. Several hypotheses on the developmental origins of health can be tested or piloted using the data collected from the Piccolipiù cohort. By pooling these data with those collected by other existing birth cohorts it will be possible to validate previous findings and to study rare exposures and outcomes.
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http://dx.doi.org/10.1186/1471-2431-14-36DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3926689PMC
February 2014

Neisseria gonorrhoeae PIII has a role on NG1873 outer membrane localization and is involved in bacterial adhesion to human cervical and urethral epithelial cells.

BMC Microbiol 2013 Nov 9;13:251. Epub 2013 Nov 9.

Novartis Vaccines and Diagnostics, S,r,L, Via Fiorentina 1, Siena 53100, Italy.

Background: Protein PIII is one of the major outer membrane proteins of Neisseria gonorrhoeae, 95% identical to RmpM (reduction modifiable protein M) or class 4 protein of Neisseria meningitidis. RmpM is known to be a membrane protein associated by non-covalent bonds to the peptidoglycan layer and interacting with PorA/PorB porin complexes resulting in the stabilization of the bacterial membrane. The C-terminal domain of PIII (and RmpM) is highly homologous to members of the OmpA family, known to have a role in adhesion/invasion in many bacterial species. The contribution of PIII in the membrane architecture and its role in the interaction with epithelial cells has never been investigated.

Results: We generated a ΔpIII knock-out mutant strain and evaluated the effects of the loss of PIII expression on bacterial morphology and on outer membrane composition. Deletion of the pIII gene does not cause any alteration in bacterial morphology or sensitivity to detergents. Moreover, the expression profile of the main membrane proteins remains the same for the wild-type and knock-out strains, with the exception of the NG1873 which is not exported to the outer membrane and accumulates in the inner membrane in the ΔpIII knock-out mutant strain.We also show that purified PIII protein is able to bind human cervical and urethral cells and that the ΔpIII knock-out mutant strain has a lower ability to adhere to human cervical and urethral cells.

Conclusion: Here we demonstrated that the PIII protein does not play a key structural role in the membrane organization of gonococcus and does not induce major effects on the expression of the main outer membrane proteins. However, in the PIII knock-out strain, the NG1873 protein is not localized in the outer membrane as it is in the wild-type strain suggesting a possible interaction of PIII with NG1873. The evidence that PIII binds to human epithelial cells derived from the female and male genital tract highlights a possible role of PIII in the virulence of gonococcus and suggests that the structural homology to OmpA is conserved also at functional level.
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http://dx.doi.org/10.1186/1471-2180-13-251DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4226279PMC
November 2013

Crystal structure of c5321: a protective antigen present in uropathogenic Escherichia coli strains displaying an SLR fold.

BMC Struct Biol 2013 Oct 7;13:19. Epub 2013 Oct 7.

Institute of Biotechnology and Biomedicine, Universitat Autònoma de Barcelona, Bellaterra 08193, Spain.

Background: Increasing rates of antimicrobial resistance among uropathogens led, among other efforts, to the application of subtractive reverse vaccinology for the identification of antigens present in extraintestinal pathogenic E. coli (ExPEC) strains but absent or variable in non-pathogenic strains, in a quest for a broadly protective Escherichia coli vaccine. The protein coded by locus c5321 from CFT073 E. coli was identified as one of nine potential vaccine candidates against ExPEC and was able to confer protection with an efficacy of 33% in a mouse model of sepsis. c5321 (known also as EsiB) lacks functional annotation and structurally belongs to the Sel1-like repeat (SLR) family. Herein, as part of the general characterization of this potential antigen, we have focused on its structural properties.

Results: We report the 1.74 Å-resolution crystal structure of c5321 from CFT073 E. coli determined by Se-Met SAD phasing. The structure is composed of 11 SLR units in a topological organisation that highly resembles that found in HcpC from Helicobacter pylori, with the main difference residing in how the super-helical fold is stabilised. The stabilising effect of disulfide bridges in HcpC is replaced in c5321 by a strengthening of the inter-repeat hydrophobic core. A metal-ion binding site, uncharacteristic of SLR proteins, is detected between SLR units 3 and 4 in the region of the inter-repeat hydrophobic core. Crystal contacts are observed between the C-terminal tail of one molecule and the C-terminal amphipathic groove of a neighbouring one, resembling interactions between ligand and proteins containing tetratricopeptide-like repeats.

Conclusions: The structure of antigen c5321 presents a mode of stabilization of the SLR fold different from that observed in close homologs of known structure. The location of the metal-ion binding site and the observed crystal contacts suggest a potential role in regulation of conformational flexibility and interaction with yet unidentified target proteins, respectively. These findings open new perspectives in both antigen design and for the identification of a functional role for this protective antigen.
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http://dx.doi.org/10.1186/1472-6807-13-19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3851747PMC
October 2013

Outer membrane vesicles reflect environmental cues in Gallibacterium anatis.

Vet Microbiol 2013 Dec 12;167(3-4):565-72. Epub 2013 Sep 12.

Department of Veterinary Disease Biology, Faculty of Health Sciences, University of Copenhagen, 1870 Frederiksberg C, Denmark.

The Gram-negative bacterium Gallibacterium anatis is a major cause of salpingitis and peritonitis in egg-laying chickens, leading to decreased egg-production worldwide. Increased knowledge of the pathogenesis and virulence factors is important to better understand and prevent the negative effects of G. anatis. To this end outer membrane vesicles (OMVs) are natural secretion products of Gram-negative bacteria, displaying an enormous functional diversity and promising results as vaccine candidates. This is the first study to report that G. anatis secretes OMVs during in vitro growth. By use of transmission electron microscopy (TEM) and SDS-PAGE, we showed that changes in in vitro growth conditions, including incubation time, media composition and temperature, affected the OMV production and protein composition. A large protein band was increased in its concentration after prolonged growth. Analysis by LC-MS/MS indicated that the band contained two proteins; the 320.1 kDa FHA precursor, FhaB, and a 407.8 kDa protein containing a von Willebrand factor type A (vWA) domain. Additional two major outer-membrane (OM) proteins could be identified in all samples; the OmpH-homolog, OmpC, and OmpA. To understand the OMV formation better, a tolR deletion mutation (ΔtolR) was generated in G. anatis. This resulted in a constantly high and growth-phase independent production of OMVs, suggesting that depletion of peptidoglycan linkages plays a role in the OMV formation in G. anatis. In conclusion, our results show that G. anatis produce OMVs in vitro and the OMV protein profile suggests that the production is an important and well-regulated ability employed by the bacteria, which may be used for vaccine production purposes.
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http://dx.doi.org/10.1016/j.vetmic.2013.09.005DOI Listing
December 2013

EsiB, a novel pathogenic Escherichia coli secretory immunoglobulin A-binding protein impairing neutrophil activation.

mBio 2013 Jul 23;4(4). Epub 2013 Jul 23.

Novartis Vaccines and Diagnostics Srl, Siena, Italy.

Unlabelled: In this study, we have characterized the functional properties of a novel Escherichia coli antigen named EsiB (E. coli secretory immunoglobulin A-binding protein), recently reported to protect mice from sepsis. Gene distribution analysis of a panel of 267 strains representative of different E. coli pathotypes revealed that esiB is preferentially associated with extraintestinal strains, while the gene is rarely found in either intestinal or nonpathogenic strains. These findings were supported by the presence of anti-EsiB antibodies in the sera of patients affected by urinary tract infections (UTIs). By solving its crystal structure, we observed that EsiB adopts a superhelical fold composed of Sel1-like repeats (SLRs), a feature often associated with bacterial proteins possessing immunomodulatory functions. Indeed, we found that EsiB interacts with secretory immunoglobulin A (SIgA) through a specific motif identified by an immunocapturing approach. Functional assays showed that EsiB binding to SIgA is likely to interfere with productive FcαRI signaling, by inhibiting both SIgA-induced neutrophil chemotaxis and respiratory burst. Indeed, EsiB hampers SIgA-mediated signaling events by reducing the phosphorylation status of key signal-transducer cytosolic proteins, including mitogen-activated kinases. We propose that the interference with such immune events could contribute to the capacity of the bacterium to avoid clearance by neutrophils, as well as reducing the recruitment of immune cells to the infection site.

Importance: Pathogenic Escherichia coli infections have recently been exacerbated by increasing antibiotic resistance and the number of recurrent contagions. Attempts to develop preventive strategies against E. coli have not been successful, mainly due to the large antigenic and genetic variability of virulence factors, but also due to the complexity of the mechanisms used by the pathogen to evade the immune system. In this work, we elucidated the function of a recently discovered protective antigen, named EsiB, and described its capacity to interact with secretory immunoglobulin A (SIgA) and impair effector functions. This work unravels a novel strategy used by E. coli to subvert the host immune response and avoid neutrophil-dependent clearance.
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http://dx.doi.org/10.1128/mBio.00206-13DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3735183PMC
July 2013

The fimbrial protein FlfA from Gallibacterium anatis is a virulence factor and vaccine candidate.

Infect Immun 2013 Jun 18;81(6):1964-73. Epub 2013 Mar 18.

Department of Veterinary Disease Biology, Faculty of Health Sciences, University of Copenhagen, Frederiksberg C, Denmark.

The Gram-negative bacterium Gallibacterium anatis is a major cause of salpingitis and peritonitis in egg-laying chickens, leading to decreased egg production worldwide. Widespread multidrug resistance largely prevents treatment of this organism using traditional antimicrobial agents, while antigenic diversity hampers disease prevention by classical vaccines. Thus, insight into its pathogenesis and knowledge about important virulence factors is urgently required. A key event during the colonization and invasion of mucosal surfaces is adherence, and recently, at least three F17-like fimbrial gene clusters were identified in the genomes of several G. anatis strains. The objective of this study was to characterize the putative F17-like fimbrial subunit protein FlfA from G. anatis 12656-12 and determine its importance for virulence. In vitro expression and surface exposure of FlfA was demonstrated by flow cytometry and immunofluorescence microscopy. The predicted function of FlfA as a fimbrial subunit protein was confirmed by immunogold electron microscopy. An flfA deletion mutant (ΔflfA) was generated in G. anatis 12656-12, and importantly, this mutant was significantly attenuated in the natural chicken host. Furthermore, protection against G. anatis 12656-12 could be induced by immunizing chickens with recombinant FlfA. Finally, in vitro expression of FlfA homologs was observed in a genetically diverse set of G. anatis strains, suggesting the potential of FlfA as a serotype-independent vaccine candidate This is the first study describing a fimbrial subunit protein of G. anatis with a clear potential as a vaccine antigen.
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http://dx.doi.org/10.1128/IAI.00059-13DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3676021PMC
June 2013

An update on the Italian Twin Register: advances in cohort recruitment, project building and network development.

Twin Res Hum Genet 2013 Feb 22;16(1):190-6. Epub 2012 Oct 22.

National Centre for Epidemiology, Surveillance and Health Promotion, Istituto Superiore di Sanità, Rome, Italy.

The Italian Twin Register has been in place for more than 10 years. Since its establishment, it has been focusing, on the one hand, on a continuous update of the existing information, and on the other hand, on new phenotypes and sample collection. Demographic data on about 140,000 twins have been updated using the municipality registries. The Italian Twin Register has been carrying out several new studies during the last few years. A birth cohort of twins, Multiple Births Cohort Study, has been started and the enrollment is ongoing. For this cohort, data on pregnancy and birth are collected, and periodical follow-ups are made. DNA is being collected for the twins and their parents. In the area of behavioral genetics, most efforts have been directed to psychological well being assessed with self-reported tools. Research on age-related traits continues with studies on arteriosclerosis development, early biomarkers in mild cognitive impairment, and the relation between lifestyle habits and mutagen sensitivity. The Italian Twin Register biobanking has grown in its size and in its know-how in terms of both technical issues and ethical procedures implementation. Furthermore, attitudes toward biobank-based research, together with willingness and motivation for donation, are being investigated. A valuable key resource for the Italian Twin Register is the possibility of linking twin data with disease registries. This approach has been yielding several important results, such as the recent study on the heritability of type 1 diabetes.
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http://dx.doi.org/10.1017/thg.2012.85DOI Listing
February 2013

[Macro factors in risk and macro differences in epigenetics].

Epidemiol Prev 2012 Mar-Apr;36(2):130-1

CNESPS, Istituto superiore di sanità, Roma, Italy.

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February 2015

Escherichia coli: great diversity around a common core.

mBio 2012 5;3(3). Epub 2012 Jun 5.

Novartis Vaccines and Diagnostics, Sienna, Italy.

Unlabelled: Escherichia coli outbreak in Germany, which resulted in more than 4,000 cases, including 908 cases of hemolytic-uremic syndrome (HUS) and at least 50 deaths, highlighted the genome plasticity of E. coli and the potential for new virulent strains to emerge. The analysis of 170 E. coli genome sequences for the presence of nine previously identified protective extraintestinal pathogenic E. coli antigens suggested the feasibility of a combination vaccine as a universal intervention against all pathogenic E. coli strains.

Importance: This article reports on the feasibility of a combination vaccine as a universal intervention against all pathogenic Escherichia coli strains.
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http://dx.doi.org/10.1128/mBio.00118-12DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3374390PMC
September 2012

FdeC, a novel broadly conserved Escherichia coli adhesin eliciting protection against urinary tract infections.

mBio 2012 10;3(2). Epub 2012 Apr 10.

Novartis Vaccines and Diagnostics Srl, Siena, Italy.

Unlabelled: The increasing antibiotic resistance of pathogenic Escherichia coli species and the absence of a pan-protective vaccine pose major health concerns. We recently identified, by subtractive reverse vaccinology, nine Escherichia coli antigens that protect mice from sepsis. In this study, we characterized one of them, ECOK1_0290, named FdeC (factor adherence E. coli) for its ability to mediate E. coli adhesion to mammalian cells and extracellular matrix. This adhesive propensity was consistent with the X-ray structure of one of the FdeC domains that shows a striking structural homology to Yersinia pseudotuberculosis invasin and enteropathogenic E. coli intimin. Confocal imaging analysis revealed that expression of FdeC on the bacterial surface is triggered by interaction of E. coli with host cells. This phenotype was also observed in bladder tissue sections derived from mice infected with an extraintestinal strain. Indeed, we observed that FdeC contributes to colonization of the bladder and kidney, with the wild-type strain outcompeting the fdeC mutant in cochallenge experiments. Finally, intranasal mucosal immunization with recombinant FdeC significantly reduced kidney colonization in mice challenged transurethrally with uropathogenic E. coli, supporting a role for FdeC in urinary tract infections.

Importance: Pathogenic Escherichia coli strains are involved in a diverse spectrum of diseases, including intestinal and extraintestinal infections (urinary tract infections and sepsis). The absence of a broadly protective vaccine against all these E. coli strains is a major problem for modern society due to high costs to health care systems. Here, we describe the structural and functional properties of a recently reported protective antigen, named FdeC, and elucidated its putative role during extraintestinal pathogenic E. coli infection by using both in vitro and in vivo infection models. The conservation of FdeC among strains of different E. coli pathotypes highlights its potential as a component of a broadly protective vaccine against extraintestinal and intestinal E. coli infections.
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http://dx.doi.org/10.1128/mBio.00010-12DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3324786PMC
June 2012

Hepatitis B: Epidemiology and prevention in developing countries.

World J Hepatol 2012 Mar;4(3):74-80

Elisabetta Franco, Laura Zaratti, Department of Public Health, University Tor Vergata, via Montpellier 1, 00133 Rome, Italy.

Hepatitis B virus (HBV) infection is a serious global public health problem. The infection may be transmitted through sexual intercourse, parenteral contact or from an infected mother to the baby at birth and, if contracted early in life, may lead to chronic liver disease, including cirrhosis and hepatocellular carcinoma. On the basis of the HBV carrier rate, the world can be divided in 3 regions of high, medium and low endemicity. The major concern is about high endemicity countries, where the most common route of infection remains vertical transmission from mother to child. Screening of all pregnant women and passive immunization with human hepatitis B immunoglobulin are not affordable for many developing countries. The infection rate can be reduced by modifying behavior, improving individual education, testing all blood donations, assuring asepsis in clinical practice and screening all pregnant women. However, availability of a safe and efficacious vaccine and adoption of appropriate immunization strategies are the most effective means to prevent HBV infection and its consequences. The unsolved problem for poorest countries, where the number of people currently infected is high, is the cost of the vaccine. A future challenge is to overcome the social and economic hurdles of maintaining and improving a prevention policy worldwide to reduce the global burden of the disease.
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http://dx.doi.org/10.4254/wjh.v4.i3.74DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3321493PMC
March 2012

Hepatitis A: Epidemiology and prevention in developing countries.

World J Hepatol 2012 Mar;4(3):68-73

Elisabetta Franco, Laura Zaratti, Department of Public Health, University Tor Vergata, via Montpellier 1, 00133 Rome, Italy.

Hepatitis A is the most common form of acute viral hepatitis in the world. Major geographical differences in endemicity of hepatitis A are closely related to hygienic and sanitary conditions and other indicators of the level of socioeconomic development. The anti-hepatitis A virus (HAV) seroprevalence rate is presently decreasing in many parts of the world, but in less developed regions and in several developing countries, HAV infection is still very common in the first years of life and seroprevalence rates approach 100%. In areas of intermediate endemicity, the delay in the exposure to the virus has generated a huge number of susceptible adolescents and adults and significantly increased the average age at infection. As the severity of disease increases with age, this has led to outbreaks of hepatitis A. Several factors contribute to the decline of the infection rate, including rising socioeconomic levels, increased access to clean water and the availability of a hepatitis A vaccine that was developed in the 1990s. For populations with a high proportion of susceptible adults, implementing vaccination programs may be considered. In this report, we review available epidemiological data and implementation of vaccination strategies, particularly focusing on developing countries.
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http://dx.doi.org/10.4254/wjh.v4.i3.68DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3321492PMC
March 2012