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21St International Pathogenic Neisseria Conference September 23 – 28, 2018

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21St International Pathogenic Neisseria Conference September 23 – 28, 2018 21st International Pathogenic Neisseria Conference September 23 – 28, 2018 Meningococcal Vaccines O1 Lower risk of invasive meningococcal disease during pregnancy: national prospective surveillance in England, 2011-2014 Sydel R. Parikh, Ray Borrow, Mary Ramsay and Shamez Ladhani Immunisation Department, Public Health England, London, UK Background: Pregnant women are considered more likely to develop serious bacterial and viral infections than non-pregnant women, but their risk of invasive meningococcal disease (IMD) is not known. We use national IMD surveillance data to identify and describe IMD cases in women of child-bearing age and to estimate disease incidence and relative risk of IMD in pregnant compared to non-pregnant women. Methods: Public Health England conducts enhanced national IMD surveillance in England; laboratory-confirmed cases are followed-up with postal questionnaires to general practitioners (GPs); all cases confirmed during 01 January 2011 to 31 December 2014 were included. Results: There were 1,502 IMD cases in women across England during the four-year surveillance period, 20.6% (n=310) were in women of reproductive age (15-44 years), four women in this group were pregnant (1.3%). Serogroup distribution of IMD cases in women of child-bearing age was similar to the overall distribution. The four cases in otherwise healthy pregnant women were confirmed across all trimesters and all survived; one case in the first trimester had a septic abortion. Both incidence (0.16 per 100,000 pregnant years) and risk (IRR: 0.21 95% confidence interval: 0.06-0.54) of IMD in pregnant women was lower compared to non-pregnant women (0.76 per 100,000 non-pregnant years). Conclusions: Pregnant women appear to be nearly five times less likely to develop IMD compared to non-pregnant women; a difference of this magnitude is unlikely to be explained by ascertainment. The ability of some meningococci to colonise and cause infections of the genital tract merits further study. Meningococcal Vaccines O2 Genetic Meningococcal Antigen Typing System (gMATS): a genotyping tool that predicts 4CMenB strain coverage in US and other countries Alessandro Muzzi1, Alessandro Brozzi1, Laura Serino1, Margherita Bodini Raquel Abad2, Dominique A Caugant3, Maurizio Comanducci, Ana Paula de Lemos4, Maria Cecilia Gorla4, Pavla Krístová5, Claudia Mikula6, Robert Mulhall7, Michael Nissen8, Hanna Nohynek9, Maria João Simões10, Ricardo Jorge11, Anna Skoczynska, Paola Stefanelli12, Muhamed-Kheir Taha13, Maija Toropainen9, Georgina Tzanakaki14, Kumaran Vadivelu1, Philip Watson15, Julio Vazquez2, Gowrisankar Rajam16, Ray Borrow17, Duccio Medini1 1GSK Vaccines, Siena, Italy; 2National Centre for Microbiology, Instituto de Salud Carlos III, Madrid, Spain; 3WHO Collaborating Centre for Reference and Research on Meningococci, Norwegian Institute of Public Health, Oslo, Norway; 4Instituto Adolfo Lutz, São Paulo; Brazil; 5National Institute of Public Health, Prague, Czech Republic; 6Austrian Agency for Health and Food Safety, Institute for Medical Microbiology and Hygiene, Graz, Austria; 7Irish Meningitis and Sepsis Reference Laboratory (IMSRL), Dublin, Ireland; 8GSK, Victoria, Australia; 9National Institute for Health and Welfare (THL), Helsinki, Finland; 10National Institute of Health, Lisbon, Portugal; 11National Medicines Institute, Warsaw, Poland; 12Department of Infectious Parasitic and Immune-mediated Diseases, Istituto Superiore di Sanità, Rome, Italy; 13Institut Pasteur, Paris, France; 14Department of Public Health, National School of Public Health, Athens, Greece; 15GSK, Rockville, MD, USA; Centers for Disease Control and Prevention, Atlanta, GA, USA; 17Public Health England, Manchester, UK Introduction: In September 2015, 4CMenB (Bexsero, GSK) was introduced into the UK National Infant Immunisation Program and has demonstrated an effectiveness of 83% after the primary series against all laboratory-confirmed invasive meningococcal serogroup B (MenB- IMD) disease. Prior to implementation, the serum bactericidal antibody assay using human complement (hSBA) and Meningococcal Antigen Typing System (MATS) were used to predict vaccine strain coverage in UK, US, and in other countries. A limitation of hSBA that is unresolved by MATS is the inability to use the assay in non-culture confirmed cases, where no live isolate is obtained. In some countries, only around half of cases are confirmed by culture, the remainder by PCR only. We examined if antigen genotyping could complement the available serological typing tools in predicting MenB strain coverage by 4CMenB. Methods: A panel of over 3900 MenB-IMD isolates from England and Wales (UK) in 2007- 2008, 2014-2015, and 2015-2016, and IMD isolates collected 2000-2015 in the US and 15 other countries, were characterized by 4CMenB antigen genotyping and/or MATS. Individual associations between antigen genotyping and MATS coverage predictions for each 4CMenB component (fHbp, NadA, NHBA and OMV) were used to define a genetic MATS (gMATS) coverage predictor. gMATS estimates were compared with MATS data and, additionally, with UK hSBA and UK vaccine effectiveness (VE) data. Results: Across national panels, gMATS predicted 4CMenB strain coverage for 81% of isolates with 92% accuracy, with highly concordant results. As with MATS estimates (66–73%), gMATS (72–73%) underestimated both the hSBA estimate of strain coverage (88%) and VE (83%) in UK for the 3 time periods. gMATS strain coverage in EU countries ranged from 58-88%, and 72- 85% in other countries, including US where the gMATS coverage estimate was 85%. These estimates were very close to the MATS coverage predictions (root-mean-square deviation 6%). Genotyping of individual 4CMenB antigens was highly predictive of their contribution to MATS coverage estimations, with accuracies >84% and >81% observed for fHbp and NHBA respectively. Conclusion: gMATS can accurately complement MATS in predicting 4CMenB strain coverage and monitoring vaccine impact. Predictions of 4CMenB strain coverage based on MATS and gMATS underestimate UK field effectiveness data. Strain coverage predictions for the US and most European countries exceed UK estimates, highlighting the potential for a positive impact of 4CMenB worldwide if implemented into national immunization programs. Meningococcal Vaccines O3 Whole-blood transcriptomics provides novel insights into the molecular mechanisms underlying the reactogenicity of the capsular group B meningococcal vaccine, 4CMenB Dylan Sheerin1, Daniel O'Connor1, Marta Valente Pinto1, Christina Dold1, Christine Rollier1, Matthew Snape1, Manish Sadarangani2, Andrew Pollard1 1Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK; 2Vaccine Evaluation Center, University of British Columbia Introduction: Invasive meningococcal disease (IMD) caused by Neisseria meningitidis is a major cause of morbidity and mortality in infants worldwide. The capsular group B meningococcal four component vaccine (4CMenB) was developed to prevent IMD caused by this capsular group and has been licensed for use in several countries. However, this vaccine is associated with increased incidence of fever in infants, particularly when administered in combination with other routine vaccines. In the present study, blood transcriptional signatures underlying febrile responses to concomitant 4CMenB immunisation were identified by RNA- sequencing (RNA-Seq) on human infant blood samples obtained following routine immunisations with or without 4CMenB. The relative contribution of each component of the 4CMenB vaccine to these responses was then determined by RNA-Seq on blood samples obtained from mice immunised with one of several vaccines including 4CMenB and each of its four components. These data were correlated and related to post-vaccine reactogenicity. Methods: Infants were randomised to receive routine immunisations (PCV13 and DTaP-IPV- Hib) with or without 4CMenB at 2 and 4 months of age (n=60). Blood samples were taken prior to immunisation at 4 months of age, then either 4 hours or 24 hours post-vaccination. Blood gene expression profiles were assessed by Illumina® 100bp paired-end RNA-sequencing. Temperature was continuously measured in these infants for the first 24 hours post-vaccination and fever was defined as a temperature ≥ 38°C. Subsequent to the infant study, 9 groups of female C57BL/6 mice (6 per group) were immunised with one of the alum-adsorbed components of the 4CMenB vaccine, the whole formulation, a heterologous outer membrane vesicle (OMV) vaccine, Eshcerichia coli lipopolysaccharide (LPS), or a control viral vector vaccine at days 0 and 14. Blood was collected 24 hours after the second dose and gene expression profiles were assessed by Illumina® 75bp paired-end RNA-sequencing. Results: Gene signatures were identified in the infant study that differentiated the both routine and routine + MenB vaccine groups. Similar transcriptional signatures were also defined in the mouse experiment that clearly distinguished between OMV groups (including 4CMenB) and recombinant protein groups. Several significantly differentially expressed genes (false discovery rate adjusted p-value < 0.05) associated with pattern recognition receptor signalling, including PGLYRP1, and pyrogenic cytokine pathways, in particular that of IL-1, were found to be common between the mouse OMV groups and infants 24 hours after receiving concomitant 4CMenB. Several genes encoding calcium ion transport proteins associated with temperature regulation at the molecular level,
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