A5030919190- Viral gastroenteritis research and epidemiology
- Escherichia coli research studies
- Clostridium difficile and Clostridium perfringens research
- Bacterial Infections and Vaccines
- Salmonella and Campylobacter epidemiology
- Pneumonia and Respiratory Infections
- Streptococcal Infections and Treatments
- Immune Response and Inflammation
- Bacteriophages and microbial interactions
- Immunotherapy and Immune Responses
- Neonatal and Maternal Infections
- Antimicrobial Resistance in Staphylococcus
- Vibrio bacteria research studies
- Cytomegalovirus and herpesvirus research
- Protein purification and stability
- Otolaryngology and Infectious Diseases
- Antibiotic Resistance in Bacteria
- Hepatitis Viruses Studies and Epidemiology
- SARS-CoV-2 and COVID-19 Research
- Monoclonal and Polyclonal Antibodies Research
- Bacterial Identification and Susceptibility Testing
- Carcinogens and Genotoxicity Assessment
- Computational Drug Discovery Methods
- Inflammasome and immune disorders
- Plant Pathogenic Bacteria Studies
Toscana Life Sciences
2015-2025
GlaxoSmithKline (Italy)
2021-2024
Global Vaccines (United States)
2018-2023
Novartis (Italy)
2015-2016
Novartis (Switzerland)
2012-2015
Recently, we developed a high yield production process for outer membrane particles from genetically modified bacteria, called Generalized Modules of Membrane Antigens (GMMA), and the corresponding simple two step filtration purification, enabling economic manufacture these use as vaccines. Using Shigella sonnei strain that was to produce penta-acylated lipopolysaccharide (LPS) with reduced endotoxicity maintain virulence plasmid encoding immunodominant O antigen component LPS, scale up GMP...
Gram-negative bacteria naturally shed particles that consist of outer membrane lipids, proteins, and soluble periplasmic components. These have been proposed for use as vaccines but the yield has problematic. We developed a high yielding production process genetically derived from human pathogen Shigella sonnei. Yields approximately 100 milligrams membrane-associated proteins per liter fermentation were obtained cultures S. sonnei ΔtolR ΔgalU at optical densities 30–45 in 5 L fermenter....
Shigella is the leading cause for dysentery worldwide. Together with several virulence factors employed invasion, presence and length of O antigen (OAg) lipopolysaccharide (LPS) plays a key role in pathogenesis. S. flexneri 2a has bimodal OAg chain distribution regulated growth-dependent manner, whereas sonnei LPS comprises monomodal OAg. Here we reveal that sonnei, but not 2a, possesses high molecular weight, immunogenic group 4 capsule, characterized by structural similarity to We found...
Significance Bacteria, such as nontyphoidal Salmonella , are responsible for a large global burden of disease. Due to limited need in developed countries and consequent lack commercial incentive, vaccines unavailable against many bacteria. Glycoconjugates constitute the standard bacterial vaccine approach, but can be costly, particularly where multivalent preparations required. This report compares low-cost vesicle-based technology, known Generalized Modules Membrane Antigens (GMMA), with...
ABSTRACT Invasive nontyphoidal Salmonella (iNTS) disease is a neglected with high mortality in children and HIV-positive individuals sub-Saharan Africa, caused primarily by Africa-specific strains of enterica serovars Typhimurium Enteritidis. A vaccine using GMMA (generalized modules for membrane antigens) from S. Enteritidis containing lipid modifications to reduce potential vivo reactogenicity under development. penta-acylated showed the greatest reduction level cytokine release human...
Shigellosis accounts for substantial morbidity and mortality worldwide is the second most common cause of moderate severe diarrhoea in children.This phase 2b study (NCT03527173), conducted between August 2018 November 2019, evaluated vaccine efficacy (VE), safety, immunogenicity a Shigella sonnei GMMA candidate (1790GAHB) adults, using S. 53 G controlled human infection model. Participants (randomized 1:1) received two doses 1790GAHB or placebo (GAHB-Placebo), at day (D) 1 D29, an oral...
Neisseria meningitidis causes epidemics of meningitis in sub-Saharan Africa. These have mainly been caused by capsular group A strains, but W and X strains are increasingly contributing to the burden disease. Therefore, an affordable vaccine that provides broad protection against meningococcal disease Africa is required.We prepared Generalized Modules for Membrane Antigens (GMMA) from a recombinant serogroup strain expressing PorA P1.5,2, which predominant among African isolates. The was...
Shigella is the second most deadly diarrheal disease among children under five years of age, after rotavirus, with high morbidity and mortality in developing countries. Currently, no vaccine widely available, increasing levels multidrug resistance make a priority for development. The single-component candidate against sonnei (1790GAHB), developed using GMMA technology, contains O antigen (OAg) portion lipopolysaccharide (LPS) as active moiety. was well tolerated immunogenic early-phase...
The high burden of disease and the long-lasting sequelae following Streptococcus pyogenes (Strep A) infections make development an effective vaccine a global health priority. Streptolysin O (SLO), is key toxin in complex pathogenesis Strep A infection. Antibodies are elicited against SLO after natural exposure represent target for vaccine-induced immunity. Here we present setup characterization hemolysis assay to measure functionality anti-SLO antibodies human sera. Assay specificity,...
Introduction Different serovars of Salmonella enterica cause systemic diseases in humans including enteric fever, caused by S. Typhi and Paratyphi A, invasive nontyphoidal salmonellosis (iNTS), mainly Typhimurium Enteritidis. No vaccines are yet available against paratyphoid fever iNTS but different strategies, based on the immunodominant O-Antigen component lipopolysaccharide, currently being tested. The O-Antigens share structural features backbone comprising mannose, rhamnose galactose as...
Background: Typhoid and paratyphoid fevers represent a global health burden, especially in Southern Asia, exacerbated by the increase antimicrobial resistance. While vaccines against Salmonella Typhi have been successfully introduced, vaccine S. Paratyphi A is not available, yet. Efforts to develop an effective targeting both serovars are currently ongoing. GVGH developing bivalent constituted Vi-CRM197 typhoid conjugate (TCV), O-antigen (O:2), also conjugated CRM197 carrier protein...
Streptococcus pyogenes leads to 500,000 deaths annually; many due rheumatic heart disease in low-income settings. Limited understanding of natural protective immunity S. hinders vaccine development. We describe the evolution serological profiles conserved vaccine-antigens and type-specific M peptides from birth throughout life course The Gambia. As placentally-transferred IgG waned after birth, evidence new exposure was seen 23% infants during first year life. Following culture-confirmed...
Shigellosis is the leading cause of diarrheal disease, especially in children low- and middle-income countries, often associated with anti-microbial resistance. Currently, there are no licensed vaccines widely available against
Group A Carbohydrate (GAC), conjugated to an appropriate carrier protein, has been proposed as attractive vaccine candidate against Streptococcus infections. Native GAC consists of a polyrhamnose (polyRha) backbone with N-acetylglucosamine (GlcNAc) at every second rhamnose residue. Both native and the polyRha have components. Here, chemical synthesis glycoengineering were used generate panel different length fragments. Biochemical analyses performed confirming that epitope motif is composed...
Shigellosis is a leading cause of diarrheal disease in low-middle-income countries (LMICs). Effective vaccines will help to reduce the burden, exacerbated by increasing antibiotic resistance, most susceptible population represented young children. A challenge for broadly protective vaccine against shigellosis cover epidemiologically relevant serotypes among >50 Shigella circulating worldwide. The GMMA platform has been proposed as an innovative delivery system O-antigens, and we have...
Despite the huge decrease in deaths caused by Shigella worldwide recent decades, shigellosis still causes over 200,000 every year. No vaccine is currently available, and morbidity of disease coupled with rise antimicrobial resistance renders introduction an effective extremely urgent. Although a clear immune correlate protection against has not yet been established, demonstration bactericidal activity antibodies induced upon vaccination may provide one means functionality protecting...
Abstract GMMA are exosomes released from engineered Gram-negative bacteria resembling the composition of outer membranes. We applied technology for development an O-Antigen (OAg) based vaccine against Shigella sonnei , most epidemiologically relevant cause shigellosis. S. OAg has been identified as a key antigen protective immunity, and able to induce anti-OAg-specific IgG response in animal models healthy adults. The contribution protein-specific antibodies induced upon vaccination with...
Shigella is associated with a significant burden of disease worldwide among individuals all ages and the major cause moderate severe diarrhea in children under five years age low- middle-income countries. Several candidate vaccines against species are currently clinical development. The investigational 1790GAHB vaccine sonnei based on GMMA (Generalized Modules for Membrane Antigens) technology. was well tolerated induced high antibody levels early-phase trials both -endemic non-endemic...
Typhoid and paratyphoid fevers have a high incidence worldwide coexist in many geographical areas, especially low-middle-income countries (LMIC) South Southeast Asia. There is extensive consensus on the urgent need for better affordable vaccines against systemic Salmonella infections. Generalized modules membrane antigens (GMMA), outer exosomes shed by bacteria genetically manipulated to increase blebbing, resemble bacterial surface where protective are displayed their native environment....
Ensuring the stability of vaccines is crucial to successfully performing global immunization programs. Outer Membrane Vesicles (OMV) are receiving great attention as vaccine platforms. OMV complex molecules and few data have been collected so far on their stability. produced by bacteria, genetically modified increase spontaneous release, simplifying production, also known Generalized Modules for Antigens (GMMA). We performed accelerated studies GMMA from different pathogens verified ability...