Antonio DiGiandomenico
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View article: P-1055. Anti-Toxin B Neutralizing Monoclonal Antibody AZD5148 Provides Protection in a <i>Clostridioides difficile</i> Gnotobiotic Piglet Model
P-1055. Anti-Toxin B Neutralizing Monoclonal Antibody AZD5148 Provides Protection in a <i>Clostridioides difficile</i> Gnotobiotic Piglet Model Open
Background Clostridioides difficile infection (CDI) cause mild to severe diarrhea and can be life threatening. Because toxin B is a clinically validated target for CDI, we have generated an anti-toxin B neutralizing monoclonal antibody (mA…
View article: Development and validation of a rabbit model of Pseudomonas aeruginosa non-ventilated pneumonia for preclinical drug development
Development and validation of a rabbit model of Pseudomonas aeruginosa non-ventilated pneumonia for preclinical drug development Open
Background New drugs targeting antimicrobial resistant pathogens, including Pseudomonas aeruginosa , have been challenging to evaluate in clinical trials, particularly for the non-ventilated hospital-acquired pneumonia and ventilator-assoc…
View article: Differential in vivo labeling with barcoded antibodies allows for simultaneous transcriptomic profiling of airway, lung tissue and intravascular immune cells
Differential in vivo labeling with barcoded antibodies allows for simultaneous transcriptomic profiling of airway, lung tissue and intravascular immune cells Open
Single-cell RNA sequencing (scRNA-seq) is the state-of-the-art approach to study transcriptomic signatures in individual cells in respiratory health and disease. However, classical scRNA-seq approaches provide no spatial information and ar…
View article: Efficacy of a <i>Pseudomonas aeruginosa</i> serogroup O9 vaccine
Efficacy of a <i>Pseudomonas aeruginosa</i> serogroup O9 vaccine Open
There are currently no approved vaccines against the opportunistic pathogen Pseudomonas aeruginosa . Among vaccine targets, the lipopolysaccharide (LPS) O antigen of P. aeruginosa is the most immunodominant protective candidate. There are …
View article: A protein-free vaccine stimulates innate immunity and protects against nosocomial pathogens
A protein-free vaccine stimulates innate immunity and protects against nosocomial pathogens Open
Traditional vaccines are difficult to deploy against the diverse antimicrobial-resistant, nosocomial pathogens that cause health care–associated infections. We developed a protein-free vaccine composed of aluminum hydroxide, monophosphoryl…
View article: Efficacy of a<i>Pseudomonas aeruginosa</i>Serogroup O9 Vaccine
Efficacy of a<i>Pseudomonas aeruginosa</i>Serogroup O9 Vaccine Open
There are currently no approved vaccines against the opportunistic pathogen Pseudomonas aeruginosa . Among vaccine targets, the lipopolysaccharide (LPS) O antigen of P. aeruginosa is the most immunodominant protective candidate. There are …
View article: Early diagnostic BioMARKers in exacerbations of chronic obstructive pulmonary disease: protocol of the exploratory, prospective, longitudinal, single-centre, observational MARKED study
Early diagnostic BioMARKers in exacerbations of chronic obstructive pulmonary disease: protocol of the exploratory, prospective, longitudinal, single-centre, observational MARKED study Open
Introduction Acute exacerbations of chronic obstructive pulmonary disease (AECOPD) play a pivotal role in the burden and progressive course of chronic obstructive pulmonary disease (COPD). As such, disease management is predominantly based…
View article: Safety, efficacy, and pharmacokinetics of gremubamab (MEDI3902), an anti-Pseudomonas aeruginosa bispecific human monoclonal antibody, in P. aeruginosa-colonised, mechanically ventilated intensive care unit patients: a randomised controlled trial
Safety, efficacy, and pharmacokinetics of gremubamab (MEDI3902), an anti-Pseudomonas aeruginosa bispecific human monoclonal antibody, in P. aeruginosa-colonised, mechanically ventilated intensive care unit patients: a randomised controlled trial Open
Background Ventilator-associated pneumonia caused by Pseudomonas aeruginosa (PA) in hospitalised patients is associated with high mortality. The effectiveness of the bivalent, bispecific mAb MEDI3902 (gremubamab) in preventing PA nosocomia…
View article: Multicomponent Pseudomonas aeruginosa Vaccines Eliciting Th17 Cells and Functional Antibody Responses Confer Enhanced Protection against Experimental Acute Pneumonia in Mice
Multicomponent Pseudomonas aeruginosa Vaccines Eliciting Th17 Cells and Functional Antibody Responses Confer Enhanced Protection against Experimental Acute Pneumonia in Mice Open
The Gram-negative pathogen Pseudomonas aeruginosa is a common cause of pneumonia in hospitalized patients. Its increasing antibiotic resistance and widespread occurrence present a pressing need for vaccines.
View article: Multicomponent <i>Pseudomonas aeruginosa</i> vaccines eliciting Th17 cells and functional antibody responses confer enhanced protection against experimental acute pneumonia in mice
Multicomponent <i>Pseudomonas aeruginosa</i> vaccines eliciting Th17 cells and functional antibody responses confer enhanced protection against experimental acute pneumonia in mice Open
The Gram-negative pathogen Pseudomonas aeruginosa is a common cause of pneumonia in hospitalized patients. Its increasing antibiotic resistance and widespread occurrence present a pressing need for vaccines. We previously showed that a P. …
View article: Microbiome Modulation as a Novel Strategy to Treat and Prevent Respiratory Infections
Microbiome Modulation as a Novel Strategy to Treat and Prevent Respiratory Infections Open
Acute and chronic lower airway disease still represent a major cause of morbidity and mortality on a global scale. With the steady rise of multidrug-resistant respiratory pathogens, such as Pseudomonas aeruginosa and Klebsiella pneumoniae,…
View article: Antivirulence Bispecific Monoclonal Antibody-Mediated Protection against Pseudomonas aeruginosa Ventilator-Associated Pneumonia in a Rabbit Model
Antivirulence Bispecific Monoclonal Antibody-Mediated Protection against Pseudomonas aeruginosa Ventilator-Associated Pneumonia in a Rabbit Model Open
Ventilator-associated pneumonia is an important clinical manifestation of the nosocomial pathogen Pseudomonas aeruginosa . We characterized the correlates of protection with MEDI3902, a bispecific human IgG1 monoclonal antibody that target…
View article: A Pseudomonas aeruginosa-Derived Particulate Vaccine Protects against P. aeruginosa Infection
A Pseudomonas aeruginosa-Derived Particulate Vaccine Protects against P. aeruginosa Infection Open
Despite numerous efforts to develop an effective vaccine against Pseudomonas aeruginosa, no vaccine has yet been approved for human use. This study investigates the utility of the P. aeruginosa inherently produced polyhydroxyalkanaote (PHA…
View article: PD-L1 <sup>+</sup> neutrophils contribute to injury-induced infection susceptibility
PD-L1 <sup>+</sup> neutrophils contribute to injury-induced infection susceptibility Open
Neutrophils abandon infection control during wound repair.
View article: Unmet needs in the management of exacerbations of chronic obstructive pulmonary disease
Unmet needs in the management of exacerbations of chronic obstructive pulmonary disease Open
Exacerbations of chronic obstructive pulmonary disease (COPD) are episodes of acute worsening of respiratory symptoms that require additional therapy. These events play a pivotal role in the natural course of the disease and are associated…
View article: Multifunctional Monoclonal Antibody Targeting Pseudomonas aeruginosa Keratitis in Mice
Multifunctional Monoclonal Antibody Targeting Pseudomonas aeruginosa Keratitis in Mice Open
A worrisome trend in the study and treatment of infectious disease noted in recent years is the increase in multidrug resistant strains of bacteria concurrent with a scarcity of new antimicrobial agents to counteract this rise. This is par…
View article: Treatment Efficacy of MEDI3902 in Pseudomonas aeruginosa Bloodstream Infection and Acute Pneumonia Rabbit Models
Treatment Efficacy of MEDI3902 in Pseudomonas aeruginosa Bloodstream Infection and Acute Pneumonia Rabbit Models Open
Pseudomonas aeruginosa is a challenge for clinicians due to increasing drug resistance and dwindling treatment options. We report on the activity of MEDI3902, an antibody targeting type 3 secretion protein PcrV and Psl exopolysaccharide, i…
View article: Frontline Science: Employing enzymatic treatment options for management of ocular biofilm-based infections
Frontline Science: Employing enzymatic treatment options for management of ocular biofilm-based infections Open
Pseudomonas aeruginosa-induced corneal keratitis is a sight-threatening disease. The rise of antibiotic resistance among P. aeruginosa keratitis isolates makes treatment of this disease challenging, emphasizing the need for alternative the…
View article: Mouse model of Gram-negative prosthetic joint infection reveals therapeutic targets
Mouse model of Gram-negative prosthetic joint infection reveals therapeutic targets Open
Bacterial biofilm infections of implantable medical devices decrease the effectiveness of antibiotics, creating difficult-to-treat chronic infections. Prosthetic joint infections (PJI) are particularly problematic because they require prol…
View article: Pseudomonas aeruginosa PcrV and Psl, the Molecular Targets of Bispecific Antibody MEDI3902, Are Conserved Among Diverse Global Clinical Isolates
Pseudomonas aeruginosa PcrV and Psl, the Molecular Targets of Bispecific Antibody MEDI3902, Are Conserved Among Diverse Global Clinical Isolates Open
Psl and PcrV are highly prevalent in global clinical isolates, suggesting MEDI3902 can mediate broad coverage against P. aeruginosa.
View article: Enhancing IgG distribution to lung mucosal tissue improves protective effect of anti–Pseudomonas aeruginosa antibodies
Enhancing IgG distribution to lung mucosal tissue improves protective effect of anti–Pseudomonas aeruginosa antibodies Open
IgG antibodies are abundantly present in the vasculature but to a much lesser extent in mucosal tissues. This contrasts with antibodies of the IgA and IgM isotype that are present at high concentration in mucosal secretions due to active d…
View article: MEDI3902 Correlates of Protection against Severe Pseudomonas aeruginosa Pneumonia in a Rabbit Acute Pneumonia Model
MEDI3902 Correlates of Protection against Severe Pseudomonas aeruginosa Pneumonia in a Rabbit Acute Pneumonia Model Open
Pseudomonas aeruginosa is among the most formidable antibiotic-resistant pathogens and is a leading cause of hospital-associated infections. With dwindling options for antibiotic-resistant infections, a new paradigm for treatment and disea…