Monoclonal Antibodies and Invasive Aspergillosis: Diagnostic and Therapeutic Perspectives

Abstract

Invasive aspergillosis (IA) is a life-threatening fungal disease that causes high morbidity and mortality in immunosuppressed patients. Early and accurate diagnosis and treatment of IA remain challenging. Given the broad range of non-specific clinical symptoms and the shortcomings of current diagnostic techniques, most patients are either diagnosed as “possible” or “probable” cases but not “proven”. Moreover, because of the lack of sensitive and specific tests, many high-risk patients receive an empirical therapy or a prolonged treatment of high-priced antifungal agents, leading to unnecessary adverse effects and a high risk of drug resistance. More precise diagnostic techniques alongside a targeted antifungal treatment are fundamental requirements for reducing the morbidity and mortality of IA. Monoclonal antibodies (mAbs) with high specificity in targeting the corresponding antigen(s) may have the potential to improve diagnostic tests and form the basis for novel IA treatments. This review summarizes the up-to-date application of mAb-based approaches in assisting IA diagnosis and therapy.

Antifungal Drug Resistance: An Emergent Health Threat

“…A promising strategy comes from inhibitors of the human cell membrane efflux proteins, or from compounds that act simultaneously on several target sites. In addition, a new viable strategy is passive immunization with monoclonal antibodies, so as to strengthen the host antifungal immune response [ 41 , 42 ], particularly in immunocompromised patients who are more prone to systemic fungal infections. Finally, three novel antifungal agents, currently in phase II/III clinical trials, might have an important role for the treatment of invasive candidiasis: phase III results showed the efficacy and safety of rezafungin [ 43 ], a novel echinocandin with extended half-life (once-weekly intravenous administration), enhanced tissue penetration/residence time, and limited drug–drug interaction potential; ibrexafungerp (phase III clinical trials) and fosmanogepix are two first-in-class antifungal drugs with acceptable oral bioavailability and broad-spectrum activity against Candida spp., including C. auris and echinocandin-resistant species ( Table 2 ) [ 43 , 44 ].…”

Clinical Manifestations of Human Exposure to Fungi

“…In immunodeficient patients, the conidia can evade this defense mechanism clearance from the respiratory tract. As such, conidia that reach deeper regions of the respiratory tract germinate and establish fungal masses inside the lungs [ 198 ].…”

“…The principal etiological agent associated with aspergillosis is A. fumigatus . However, other non- fumigatus Aspergillus species also contribute to the disease outset; among these are: A. niger , A. terreus , A. nidulans , and A. oryzae ( Table S2 ) [ 198 , 199 ].…”

“…Aspergillosis risk factors include the use of medications (antibacterial agents, corticosteroids, anti-tuberculosis drugs, immunosuppressants), the existence of underlying medical conditions (chronic obstructive pulmonary disease, severe viral pneumonia, severe influenza, severe COVID, tuberculosis, sarcoidosis, pneumoconiosis, lung cancer, liver failure, liver cirrhosis, neutropenia, hematological malignancies, transplantation, HIV/AIDS, and other immunodeficiency diseases) [ 198 , 200 , 201 ]. Some additional factors may also play a role in the disease onset, such as malnutrition, marijuana smoking, and a stay in a hospital setting (nosocomial infection) [ 199 , 202 ].…”

Metagenomic Next-Generation Sequencing Assists in the Diagnosis of Mediastinal Aspergillus fumigatus Abscess in an Immunocompetent Patient: A Case Report and Literature Review

“…Invasive aspergillosis is a life-threatening infectious disease associated with high mortality in immunocompromised hosts; 1 Aspergillus fumigatus is an opportunistic fungal pathogen, and Aspergillus fumigatus infection usually occurs in the lungs. However, mediastinal Aspergillus fumigatus infection is rare, especially in immunocompetent hosts.…”