Immunotherapy against Systemic Fungal Infections Based on Monoclonal Antibodies

Abstract

The increasing incidence in systemic fungal infections in humans has increased focus for the development of fungal vaccines and use of monoclonal antibodies. Invasive mycoses are generally difficult to treat, as most occur in vulnerable individuals, with compromised innate and adaptive immune responses. Mortality rates in the setting of our current antifungal drugs remain excessively high. Moreover, systemic mycoses require prolonged durations of antifungal treatment and side effects frequently occur, particularly drug-induced liver and/or kidney injury. The use of monoclonal antibodies with or without concomitant administration of antifungal drugs emerges as a potentially efficient treatment modality to improve outcomes and reduce chemotherapy toxicities. In this review, we focus on the use of monoclonal antibodies with experimental evidence on the reduction of fungal burden and prolongation of survival in in vivo disease models. Presently, there are no licensed monoclonal antibodies for use in the treatment of systemic mycoses, although the potential of such a vaccine is very high as indicated by the substantial promising results from several experimental models.

In Vitro and In Vivo Effect of Peptides Derived from 14-3-3 Paracoccidioides spp. Protein

“…Considering these factors, the search for alternatives to prevention and treatment is urgent. Different approaches have been investigated in the search for a safe and effective immunization or vaccination therapy for invasive mycoses such as the use of monoclonal antibodies [ 55 ], peptide vaccine [ 56 , 57 ], vaccines based on nanotechnology [ 58 ], and DNA vaccine [ 59 ].…”

Immunomodulation for the Treatment of Fungal Infections: Opportunities and Challenges

“…The child was treated with dupilumab, a monoclonal antibody that blocks the alpha chain common to the interleukin-4 and interleukin-13 receptors, and it resulted in rapid resolution of the clinical symptoms (Tsai et al, 2020 ). Moreover, as reviewed in Boniche et al using monoclonal antibody-based immunomodulation therapies was shown to have a promising therapeutic potential over a wide range of fungal infections, including, Histoplasma capsulatum, Aspergillus fumigatus, Pneumocystis jirovecii, Cryptococcus neoformans, Sporothrix schenckii , and Blastomyces dermatitidis (Boniche et al, 2020 ). However, the majority of clinically utilized mAbs are chimeric, humanized or, fully human IgG1, produced by hybridoma technology, and the production of these mABs demands good manufacturing practice (GMP) conditions (Strohl, 2014 ; Rudkin et al, 2018 ).…”

Advances in Fungal Peptide Vaccines

“…One of the first and most difficult challenges in working with fungal vaccines is the need to determine the target population in which a vaccine is applied, as many invasive mycoses have a predilection for causing disease in immunosuppressed individuals [7][8][9]. Specific knowledge is required regarding the type of protective response necessary to combat a specific fungus and then there is a need to translate this information into a formulation that remains safe and effective in an immunocompromised host [20,21].…”

“…The absence of mass market appeal has been presented as the major obstacle in fungal vaccine development [2][3][4][5][6]. However, this situation is changing rapidly as the incidence of invasive mycoses has increased with the rising numbers of individuals with increased risk for fungal disease, including cancer patients receiving chemotherapy, bone marrow transplant recipients, individuals with acquired immune deficiency syndrome (AIDS), individuals treated with immune function inhibitors, and others patients with different types of immunosuppression [7][8][9]. Additionally, certain fungi, such as Candida auris, an emerging multi-drug resistant pathogen, have received significant global media attention.…”