GMMA as an alternative carrier for a glycoconjugate vaccine against Group A streptococcus

Group A Streptococcus (GAS) causes about 500,000 annual deaths globally, and no vaccines are currently available. The Group A Carbohydrate (GAC), conserved across all GAS serotypes, conjugated to an appropriate carrier protein, represents a promising vaccine candidate. Here, we explored the possibility to use Generalized Modules for Membrane Antigens (GMMA) as an alternative carrier system for GAC, exploiting their intrinsic adjuvant properties. Immunogenicity of GAC-GMMA conjugate was evaluated in different animal species in comparison to GAC-CRM197; and the two conjugates were also compared from a techno-economic point of view. GMMA proved to be a good alternative carrier for GAC, resulting in a higher immune response compared to CRM197 in different mice strains, as verified by ELISA and FACS analyses. Differently from CRM197, GMMA induced significant levels of anti-GAC IgG titers in mice also in the absence of Alhydrogel. In rabbits, a difference in the immune response could not be appreciated; however, antibodies from GAC-GMMA-immunized animals showed higher affinity toward purified GAC antigen compared to those elicited by GAC-CRM197. In addition, the GAC-GMMA production process proved to be more cost-effective, making this conjugate particularly attractive for low- and middle-income countries, where this pathogen has a huge burden

Impact of routine vaccination against Haemophilus influenzae type b in The Gambia: 20 years after its introduction

Background: In 1997, The Gambia introduced three primary doses of Haemophilus influenzae type b (Hib) conjugate vaccine without a booster in its infant immunisation programme along with establishment of a population-based surveillance on Hib meningitis in the West Coast Region (WCR). This surveillance was stopped in 2002 with reported elimination of Hib disease. This was re-established in 2008 but stopped again in 2010. We aimed to re-establish the surveillance in WCR and to continue surveillance in Basse Health and Demographic Surveillance System (BHDSS) in the east of the country to assess any shifts in the epidemiology of Hib disease in The Gambia. Methods: In WCR, population-based surveillance for Hib meningitis was re-established in children aged under-10 years from 24 December 2014 to 31 March 2017, using conventional microbiology and Real Time Polymerase Chain Reaction (RT-PCR). In BHDSS, population-based surveillance for Hib disease was conducted in children aged 2-59 months from 12 May 2008 to 31 December 2017 using conventional microbiology only. Hib carriage survey was carried out in pre-school and school children from July 2015 to November 2016. Results: In WCR, five Hib meningitis cases were detected using conventional microbiology while another 14 were detected by RT-PCR. Of the 19 cases, two (11%) were too young to be protected by vaccination while seven (37%) were unvaccinated. Using conventional microbiology, the incidence of Hib meningitis per 100 000-child-year (CY) in children aged 1-59 months was 0.7 in 2015 (95% confidence interval (CI) = 0.0-3.7) and 2.7 (95% CI = 0.7-7.0) in 2016. In BHDSS, 25 Hib cases were reported. Nine (36%) were too young to be protected by vaccination and five (20%) were under-vaccinated for age. Disease incidence peaked in 2012-2013 at 15 per 100 000 CY and fell to 5-8 per 100 000 CY over the subsequent four years. The prevalence of Hib carriage was 0.12% in WCR and 0.38% in BHDSS. Conclusions: After 20 years of using three primary doses of Hib vaccine without a booster Hib transmission continues in The Gambia, albeit at low rates. Improved coverage and timeliness of vaccination are of high priority for Hib disease in settings like Gambia, and there are currently no clear indications of a need for a booster dose

Facile Preparation of Fluorescent Neoglycoproteins Using p-Nitrophenyl Anthranilate as a Heterobifunctional Linker

A facile preparation of neoglycoconjugates has been developed with a commercially available chemical, p-nitrophenyl anthranilate (PNPA), as a heterobifunctional linker. The two functional groups of PNPA, the aromatic amine and the p-nitrophenyl ester, are fully differentiated to selectively conjugate with glycans and other biomolecules containing nucleophiles. PNPA is efficiently conjugated with free reducing glycans via reductive amination. The glycan−PNPA conjugates (GPNPAs) can be easily purified and quantified by UV absorption. The active p-nitrophenyl ester in the GPNPA conjugates readily reacts with amines under mild conditions, and the resulting conjugates acquire strong fluorescence. This approach was used to prepare several fluorescent neoglycoproteins. The neoglycoproteins were covalently printed on activated glass slides and were bound by appropriate lectins recognizing the glycans

H. pylori-infection and antibody immune response in a rural Tanzanian population

BACKGROUND: Helicobacter pylori (H. pylori) infection is ubiquitous in sub-Saharan Africa, but paradoxically gastric cancer is rare. METHODS: Sera collected during a household-based survey in rural Tanzania in 1985 were tested for anti-H. pylori IgG and IgG subclass antibodies by enzyme immunoassay. Odds ratios (OR) and confidence intervals (CI) of association of seropositivity with demographic variables were computed by logistic regression models. RESULTS: Of 788 participants, 513 were aged ≤17 years. H. pylori seropositivity increased from 76% at 0–4 years to 99% by ≥18 years of age. Seropositivity was associated with age (OR 11.5, 95% CI 4.2–31.4 for 10–17 vs. 0–4 years), higher birth-order (11.1; 3.6–34.1 for ≥3(rd )vs. 1(st )born), and having a seropositive next-older sibling (2.7; 0.9–8.3). Median values of IgG subclass were 7.2 for IgG1 and 2.0 for IgG2. The median IgG1/IgG2 ratio was 3.1 (IQR: 1.7–5.6), consistent with a Th2-dominant immune profile. Th2-dominant response was more frequent in children than adults (OR 2.4, 95% CI 1.3–4.4). CONCLUSION: H. pylori seropositivity was highly prevalent in Tanzania and the immunological response was Th2-dominant. Th2-dominant immune response, possibly caused by concurrent bacterial or parasitic infections, could explain, in part, the lower risk of H. pylori-associated gastric cancer in Africa

Interlaboratory comparison of a multiplex immunoassay that measures human serum IgG antibodies against six-group B streptococcus polysaccharides.

Measurement of IgG antibodies against group B streptococcus (GBS) capsular polysaccharide (CPS) by use of a standardized and internationally accepted multiplex immunoassay is important for the evaluation of candidate maternal GBS vaccines in order to compare results across studies. A standardized assay is also required if serocorrelates of protection against invasive GBS disease are to be established in infant sera for the six predominant GBS serotypes since it would permit the comparison of results across the six serotypes. We undertook an interlaboratory study across five laboratories that used standardized assay reagents and protocols with a panel of 44 human sera to measure IgG antibodies against GBS CPS serotypes Ia, Ib, II, III, IV, and V. The within-laboratory intermediate precision, which included factors like the lot of coated beads, laboratory analyst, and day, was generally below 20% relative standard deviation (RSD) for all six serotypes, across all five laboratories. The cross-laboratory reproducibility was < 25% RSD for all six serotypes, which demonstrated the consistency of results across the different laboratories. Additionally, anti-CPS IgG concentrations for the 44-member human serum panel were established. The results of this study showed assay robustness and that the resultant anti-CPS IgG concentrations were reproducible across laboratories for the six GBS CPS serotypes when the standardized assay was used

A quantitative study of systematic uncertainties due to QED corrections in accurate Compton polarimetry experiments

International audienceSeveral new high-energy physics accelerators will exploitbeam polarization as a core part of their program. In several casesthe beam polarization needs to be accurately measured with aprecision better than one per-mille. At this level of precision, α$^{3}$ QED corrections must be accounted for. In this paper, weestimate the related correction for the detectors considered forseveral projects as ILC and FCC-ee. Two different techniques toextract the beam polarization are investigated and found to providecomplementary information. The related measurements are dominated bydifferent sources of systematic uncertainties, either related to QEDcorrections or likely to uncontrolled variations of experimentalconditions at the per-mille level. It is found in particular thatthe measurement of the spatial distribution of photons, besidesexperimental challenges, is more sensitive to QED corrections thanthe technique consisting in measuring electrons spatial and energydistribution

Portfolio dans la formation tout au long de la vie

Actes de l'atelier L’apprenant, acteur principal de son parcours tout au long de sa vie. Atelier des ORPHEE-RDV1. Description et principaux objectifs Chaque personne devrait avoir la possibilité d'apprendre tout au long de sa vie afin d'acquérir les connaissances et les compétences nécessaires pour réaliser ses aspirations et contribuer à la société [1]. Dans son rapport sur la stratégie de l'éducation 2014-2021 [2], l'UNESCO stipule que l'un des objectifs stratégiques de la fin de la décennie est le développement des systèmes éducatifs favorisant un tel apprentissage, à la fois inclusif et de qualité. Dans ce contexte, se pose la question cruciale du suivi et de l'agrégation des compétences de chaque apprenant, accompagnant son dévelop-pement personnel tout au long de sa vie. Ainsi, on peut formuler l'objectif général de ce grand challenge comme étant la facilitation d'accès aux compétences d'un apprenant d'une manière unifiée pendant toute sa vie. Pour y parvenir, nous nous penchons sur la notion de portfolio électronique ou ePortfolio dont le but est de regrouper sous forme numérique l'ensemble des preuves des compétences acquises par un apprenant. Le ePortfolio, déjà préconisé par des nombreuses études comme prometteur pour le développement et la valorisation de l'apprenant [3], peut-être vu comme une collection d'éléments reflétant les efforts, les progrès et les réalisations d'une personne. Il représente une fenêtre publique pour mettre en valeur les réalisations personnelles. Il existe de nombreux avantages à avoir un ePortfolio dont une communication facilitée et une source d'évaluation des compé-tences pour les formateurs et eventuellement des employeurs. Parmi les outils existants, on peut citer Lorfolio [4] qui propose à chaque résident du territoire GrandEst de valoriser son parcours face aux futurs employeurs. Toutefois, cette initiative est sous-exploitée, en 6 ans d'existence, moins de mille profils ont été remplis pour un bassin d'environ 5,5 million d'habitants. Plusieurs raisons expliquent le manque d'appétence pour ces outils [5] : (1) il est nécessaire d'accompagner les usagers dans l'élicitation de leurs compétences ; (2) les outils sont axés sur la valori-sation et non sur le développement personnel ; (3) les outils ne permettent pas aux usagers de valider les compétences acquises hors les cadres formels de l'éducation et de l'emploi ; (4) les différents outils ne sont pas interopérables avec les systèmes existants et ne mettent pas le contrôle des données entre les mains des usagers. Pour répondre à ces problématiques, nous souhaitons étendre la notion de ePortfolio à toutes les compétences acquises tout au long de la vie et permettre de le connecter aux diverses entités nécessitant d'y accéder à travers des formats d'échanges ouverts