Intensified high yield production of GMMA based vaccines for high burden neglected disease

Vaccines are among the most important public health interventions currently available. The global demand for vaccines is growing due to global population growth, ongoing global immunization campaigns and the increase of antibiotic-resistant bacteria. Vaccines are of high importance in Low- and Middle-Income Countries (LMIC) where millions of deaths occur annually due to vaccines-preventable diseases. Global coverage would need at least 200 million doses annually of a two-dose vaccine to cover the at-risk birth cohort, and considerably more for catch up vaccination during a roll out phase. Especially for vaccines against diseases in LMIC, there is a major added constraint: the vaccine production cost per unit and manufacturing facilities investments must be minimized to ensure the vaccines will be both viable and sustainable. For diseases caused by Gram-negative bacteria, the vaccine platform based on the GMMA technology is promising. GMMA are highly immunogenic outer membrane exosomes produced from genetically engineered bacteria modified for high yield hyper-blebbing that can be purified with minimal downstream processing. Simple robust scalable processes make GMMA ideal for cost-conscious vaccines. Please click Download on the upper right corner to see the full abstract

Analytical development to support manufacturing of a sustainable vaccine against Invasive Nontyphoidal Salmonellosis

GVGH is developing a candidate trivalent Salmonella vaccine to fight invasive nontyphoidal Salmonellosis (iNTS) and typhoid fever, especially aimed for sub-Saharan Africa to impact disease burden and to reduce anti-microbial resistance spread. This trivalent vaccine may be the only viable option for a sustainable iNTS vaccine in sub-Saharan Africa over the separate administration of Typhoid Conjugate Vaccines (TCV) and a vaccine against iNTS. GVGH generated the iNTS-TCV formulation by combining the GMMA technology for the iNTS components, S. Typhimurium (STm) and S. Enteritidis (SEn) GMMA adsorbed on Alhydrogel, and the Vi-CRM197 glycoconjugate, originally developed by GVGH and recently WHO prequalified as TCV TYPHIBEV by Biological E Ltd (Hyderabad, India). A set of analytical methods to support the vaccine lot release and characterization have been developed by GVGH. In particular, to quantify the key active ingredients of iNTS components a competitive ELISA-based method (FAcE, Formulated Alhydrogel competitive ELISA assay) has been setup and characterized in terms of specificity, accuracy and precision. Vi component is instead characterized by means of HPAEC-PAD method, able to specifically identify and quantify the total polysaccharide in the final drug product. With regard to safety assessment, a Monocyte Activation Test (MAT) has been developed as to monitor the intrinsic pyrogenicity of GMMA-based vaccines and applied as surveillance test for the Phase 1 clinical lot, with the plan to set release criteria based on clinical experience. In vivo potency assay has been set to characterize the immunogenicity of vaccine lots in comparison to freshly formulated material at the time of release and during real-time stability. A significant antibody response to each of the active ingredients of the trivalent vaccine is raised in mice and assessed by Parallel Line Assay. Overall, the applied analytical panel and the results support the development of an iNTS-TCV vaccine as a viable option for a sustainable iNTS vaccine in sub-Saharan Africa

A scalable method for O-antigen purification applied to different Salmonella serovars

The surface lipopolysaccharide of Gram-negative bacteria is both a virulence factor and a B-cell antigen. Antibodies against O-antigen of lipopolysaccharide may confer protection against infection, and O-antigen conjugates have been designed against multiple pathogens. Here, we describe simplified methodology for extraction and purification of O-antigen-core portion of Salmonella lipopolysaccharide, suitable for large scale production. Lipopolysaccharide extraction and delipidation is performed by acetic acid hydrolysis of whole bacterial culture, and can take place directly in a bioreactor, without previous isolation and inactivation of bacteria. Further O-antigen-core purification consists of rapid filtration and precipitation steps, without using enzymes or hazardous chemicals. The process was successfully applied to different Salmonella enterica serovars (Paratyphi A, Typhimurium and Enteritidis), obtaining good yields of high quality material, suitable for conjugate vaccines preparations

A ciência na primeira página: análise das capas de três jornais brasileiros Science on the front page: an analysis of the covers of three Brazilian newspapers

Diversos estudos se dedicaram a compreender como temas relacionados a ciência e tecnologia (C&T) são cobertos pela mídia, mas poucos analisaram a presença desses temas na primeira página dos jornais. Neste estudo, fizemos uma análise de conteúdo das chamadas de capa relativas a temas de C&T veiculadas em 2006, em um jornal de elite nacional (Folha de S.Paulo) e dois jornais regionais (Jornal do Commercio, de Pernambuco, e Zero Hora, do Rio Grande do Sul). Observamos que os três jornais, embora com intensidade diferente, deram espaço a C&T na capa. Folha de S.Paulo levou o tema às capas com maior frequência, ao passo que Zero Hora foi o jornal que lhe deu mais destaque na capa.<br>Many studies have tried to understand how the media covers topics related to science and technology (S&T) but few have examined the presence of these topics on the front pages of newspapers. This study analyzes the content of front-page leads about S&T in 2006, focusing on one elite national paper (Folha de S.Paulo) and two regional papers (Jornal do Commercio, from Pernambuco, and Zero Hora, from Rio Grande do Sul). It was noted that all three papers devoted front-page space to S&T, although to differing degrees. Folha de S.Paulo featured the topic more often, while Zero Hora highlighted it the most on its front pages

Raccomandazioni cliniche in odontostomatologia

L’Organizzazione Mondiale della Sanità considera la salute orale come parte integrante, non solo dello stato di salute generale, ma anche della qualità della vita di ciascun individuo. In tale ottica, in accordo e con il sostegno del mondo professionale e della comunità scientifica di questo settore, le raccomandazioni cliniche in odontostomatologia contenute nel presente volume forniscono indicazioni e definiscono standard di intervento per la prevenzione e la cura delle più comuni patologie del cavo orale nonché per l’identificazione di percorsi terapeutici appropriati a supporto degli operatori pubblici e privati. Esse costituiscono, inoltre, uno strumento utile per mantenere alto il livello di qualità delle cure in questo periodo storico, nel quale, se da un lato crescono le opportunità tecniche di cura e la potenziale domanda delle stesse, dall’altro la riduzione delle risorse economiche a disposizione dei cittadini tende a limitare l’accesso all’offerta professionale privata e, al contempo, i processi di razionalizzazione dell’allocazione dei fondi nel SSN rendono più difficile l’accesso alle strutture pubbliche. L’individuazione di raccomandazioni cliniche chiaramente definite e rese pubbliche può facilitare la condivisione degli obiettivi e dei percorsi terapeutici tra odontoiatra e paziente, migliorare la comunicazione e, in ultima analisi, accrescere la fiducia sia nei riguardi del proprio specifico professionista che del “sistema delle cure” più in generale. La revisione delle “Raccomandazioni cliniche in odontostomatologia” si è resa necessaria in considerazione del cambiamento dell’evidenza scientifica, dell’immissione in commercio di nuovi materiali e dell’utilizzo di nuove tecnologie, specie in ambito protesico. Come per la precedente, alla realizzazione di questa edizione ha contribuito un ampio gruppo di docenti ed esperti delle singole branche odontoiatriche insieme alle più importanti e rappresentative Associazioni professionali e ai componenti della Commissione Albo Odontoiatri (CAO) nazionale