Monoclonal Antibodies as Tools to Combat Fungal Infections

Abstract

Antibodies represent an important element in the adaptive immune response and a major tool to eliminate microbial pathogens. For many bacterial and viral infections, efficient vaccines exist, but not for fungal pathogens. For a long time, antibodies have been assumed to be of minor importance for a successful clearance of fungal infections; however this perception has been challenged by a large number of studies over the last three decades. In this review, we focus on the potential therapeutic and prophylactic use of monoclonal antibodies. Since systemic mycoses normally occur in severely immunocompromised patients, a passive immunization using monoclonal antibodies is a promising approach to directly attack the fungal pathogen and/or to activate and strengthen the residual antifungal immune response in these patients.

Monoclonal antibodies targeting surface exposed epitopes of Candida albicans cell wall proteins confer in vivo protection in an infection model

“…With the advent of mAb technology, several groups have reported the development of protective antibodies as a central part of a patient’s recovery from infection (31). These mAbs typically recognise antigens that are unique to the fungus and include fungal cell wall polysaccharides and a small number of cell wall proteins (Als3, Sap2, Hsp90 and Hry1) involved in cell growth, virulence and pathogenesis, as reviewed in (15) (32). Utr2 and Pga31 are CWPs covalently linked to the fungal cell wall with their level of expression affected by carbon source (33) and to infection-associated stress-conditions, including external stimuli such as challenge with antifungal agents (34).…”

“…Whilst CWPs define the success of many fungal pathogens, some may also provide an "Achilles' heel" which can be exploited in therapy. Neutralising antibodies against CWPs have been detected in patients' sera and therefore represent an important source of antigens/epitopes for vaccine generation and therapeutic antibody development (15). GPI-anchored CWPs, such as Pga31 and Utr2, play important roles in cell wall integrity and assembly (16).…”

Evaluating the Cost of Pharmaceutical Purification for a Long-Duration Space Exploration Medical Foundry

“…The medical significance of mAb therapies and the highly developed and specialized purification technology provide a fertile ground for techno-economic feasibility analysis of an in situ resource utilization (ISRU)-based pharmaceutical foundry for space. The first reason is that there are mAb therapies commercially approved or in development for multiple important disease states of spaceflight including osteoporosis ( Faienza et al, 2018 ), migraines/headaches ( Schuster and Rapoport, 2016 ), seizure ( Zhao et al, 2017 ), pneumonia ( Hua et al, 2014 ), ocular herpes ( Krawczyk et al, 2015 ), otitis media ( Iino et al, 2019 ), various oncological indications ( Zahavi and Weiner, 2020 ), and fungal infections ( Ulrich and Ebel, 2020 ). A second reason is that degradation products of mAb therapies are known to result in, not just reduced efficacy, but also deleterious effects (e.g., harmful immune reactions in patients) that further compound concerns of pharmaceutical stability over a long-duration mission ( Laptoš and Omersel, 2018 ).…”

The Pathogenesis of Aspergillus fumigatus, Host Defense Mechanisms, and the Development of AFMP4 Antigen as a Vaccine

“…However, recent research reported that β-1,3-glucan specific antibodies could not only inhibit Aspergillus hyphae but also protect CD2F1 mice against Aspergillus challenge ( Matveev et al 2019 ). Although it is generally acknowledged that T cells immunity plays a vital role in combating fungal aspergillosis (Diaz- Arevalo and Kalkum 2017 ), there are a variety of ways, such as opsonization, complement activation, and virulence factors neutralization, in which antibodies affect T cells response and suppress the growth, adherence, and germination of fungi ( Liedke et al 2017 ; Ulrich and Ebel 2020 ).…”