Michela Brazzoli

Single‐Cell Profiling Identifies Skin‐Resident Memory CD4 + T Cells as a Potential Correlate of Immunity During Staphylococcus aureus Skin Infection

Jonah Clegg, Giovanni Cova, Alberto Carignano, Megan Smith et autres

ABSTRACT Staphylococcus aureus is a leading cause of skin and soft tissue infections (SSTIs), yet the cellular mediators of protective memory remain incompletely defined. Using a self‐resolving murine SSTI model, we combined longitudinal single‐cell RNA sequencing with flow cytometry to characterize immune …

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Galleria mellonella model recapitulates Staphylococcus aureus hemolysin toxicity and antibody-mediated mechanisms of protection

Edoardo Cherubini, Andrea Paola Mandelli, Lucia Henrici De Angelis, Michela Brazzoli et autres

The study of host-pathogen interactions in animal infection models has clarified mechanisms of bacterial pathogenicity and supported the development of preventive and therapeutic strategies. Although many virulence factors have been identified in vivo using mammals such as mice and rats, this work …

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Safety, Efficacy, and Immunogenicity of a Multivalent Adjuvanted Staphylococcus aureus Vaccine in Adults With Recent Skin and Soft Tissue Infections: An Observer-Blind, Randomized, Placebo-Controlled, Multinational Phase 1/2 Trial

Eugene Athan, Richard Neil Greenberg, David Baker, Ruchir Shah et autres

BACKGROUND: A vaccine that prevents Staphylococcus aureus skin and soft tissue infections (SA-SSTIs) would have a major impact on public health. METHODS: A two-part randomized study began with a phase 1, first-in-human, dose-escalation that tested the safety of the five-antigen S. aureus …

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Unraveling the mouse model of Staphylococcus aureus bacteremia and sepsis: a systematic approach to better characterize host/pathogen interactions

Serena Vastola, Marco Tortoli, Stefania Torricelli, Michela Brazzoli et autres

ABSTRACT Staphylococcus aureus is a pathobiont whose primary human reservoirs are nares, pharynx, intestines, and skin. When specific conditions in the host are altered, it can cause a wide variety of human diseases, including bacteremia and sepsis. Preclinical in vivo models mimicking …

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A novel GMMA-based gonococcal vaccine demonstrates functional immune responses in mice

Marco Spinsanti, Elisabetta Monaci, Giacomo Romagnoli, Giada Buffi et autres

Gonorrhea, caused by Neisseria gonorrhoeae (GC) represents a significant public health threat that may be mitigated by an effective vaccine. Vaccines containing N. meningitidis outer membrane vesicles (OMVs), such as 4CMenB, demonstrated moderate effectiveness in preventing GC infections. Here, we developed NgG, …

Staphylococcus aureus-specific TIGIT+ Treg are present in the blood of healthy subjects – a hurdle for vaccination?

Jonah Clegg, Malgorzata Ewa Mnich, Alberto Carignano, Giovanni Cova et autres

Staphylococcus aureus poses an enormous burden of morbidity and mortality worldwide. Making an efficacious vaccine has however proven extremely challenging. Due to colonizing interactions, pre-existing S. aureus -specific CD4 + T cells are often found in the human population and yet a …

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Cytokine Biomarkers of Exacerbations in Sputum From Patients With Chronic Obstructive Pulmonary Disease: A Prospective Cohort Study

Sonia Budroni, Marianna Taccone, Maria Laura Stella, Susanna Aprea et autres

BACKGROUND: We determined the relationships between cytokine expression in sputum and clinical data to characterize and understand chronic obstructive pulmonary disease (COPD) exacerbations in people with COPD. METHODS: We measured 30 cytokines in 936 sputum samples, collected at stable state and exacerbation …

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Vaccination with staphylococcal protein A protects mice against systemic complications of skin infection recurrences

Andrea Paola Mandelli, Greta Magri, Marco Tortoli, Stefania Torricelli et autres

Skin and soft tissue infections (SSTIs) are the most common diseases caused by Staphylococcus aureus (S. aureus), which can progress to threatening conditions due to recurrences and systemic complications. Staphylococcal protein A (SpA) is an immunomodulator antigen of S. aureus, which allows …

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Molecular Signature of Monocytes Shaped by the Shigella sonnei 1790-Generalized Modules for Membrane Antigens Vaccine

Serena Tondi, Emilio Siena, Ahmed Essaghir, Benoît Bozzetti et autres

Shigellosis, an acute gastroenteritis infection caused by Shigella species, remains a public health burden in developing countries. Recently, many outbreaks due to Shigella sonnei multidrug-resistant strains have been reported in high-income countries, and the lack of an effective vaccine represents a major …

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Straight to the point: targeted mRNA-delivery to immune cells for improved vaccine design

Bruna Clemente, Maxime Denis, Camila Pedroso Silveira, Francesca Schiavetti et autres

With the deepening of our understanding of adaptive immunity at the cellular and molecular level, targeting antigens directly to immune cells has proven to be a successful strategy to develop innovative and potent vaccines. Indeed, it offers the potential to increase vaccine …

Challenges in development of vaccines directed toward antimicrobial resistant bacterial species

Michela Brazzoli, Diego Piccioli, Federico Marchetti

Antimicrobial resistance (AMR) is considered by WHO one of the top ten public health threats. New control strategies involving concerted actions of both public and private sectors need to be developed. Vaccines play a major role in controlling the spread of AMR …

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Systems analysis of human responses to an aluminium hydroxide-adsorbed TLR7 agonist (AS37) adjuvanted vaccine reveals a dose-dependent and specific activation of the interferon-mediated antiviral response

Emilio Siena, Francesca Schiavetti, Erica Borgogni, Marianna Taccone et autres

The candidate Adjuvant System AS37 contains a synthetic toll-like receptor agonist (TLR7a) adsorbed to alum. In a phase I study (NCT02639351), healthy adults were randomised to receive one dose of licensed alum-adjuvanted meningococcal serogroup C (MenC-CRM197) conjugate vaccine (control) or MenC-CRM197 conjugate …

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