Immunotherapy against Systemic Fungal Infections Based on Monoclonal Antibodies.

Camila Boniche,Suélen Andreia Rossi,Luiz R Travassos,Filipe Vieira Barbalho,Carlos Pelleschi Taborda,Brenda Kischkel,Joshua D Nosanchuk,Ágata Nogueira D’Aurea Moura

doi:10.3390/jof6010031

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.

Highlights

A focus on therapies based on monoclonal antibodies (mAbs) against fungal infections [9], especially mycoses which do not respond to prophylactic vaccination [27], is urgently needed
This review aims at updating the progress made in the field of therapeutic antifungal vaccines based on mAbs against systemic mycoses
The role of antibody mediated immunity in fungal infections was elucidated as a result of the advances made ~40 years ago in hybridoma technology that allows for the generation of mAbs [25,26,28,29]

Summary

Introduction

The increased numbers of immunocompromised hosts, global travel, climate alterations, and the common use of invasive devices have resulted in significant increases in rates of invasive mycoses. Years of prolonged use of these drugs in many areas such as medical and veterinary clinics and agricultural sites have caused important modifications in the global microbiome, with the emergence of drug resistant fungal pathogens [15,24] This resistance to antifungal drugs shown by many fungal species is mainly associated with immunocompromised individuals [9]. Motivated by the recent advances in our understanding of host-fungus interactions, enriched by powerful molecular biological tools [1,15], there has been an exciting increased interest in mAbs as a possible alternative modality to treat mycoses, leading to a renewed focus on promising anti-fungal immunotherapies [1,16,26] In this scenario, a focus on therapies based on mAbs against fungal infections [9], especially mycoses which do not respond to prophylactic vaccination [27], is urgently needed. It covers the current development of mAb vaccines and the contemporary challenges faced in this research field

Immunotherapy Based on Monoclonal Antibodies

Monoclonal Antibody Therapy Approaches in Systemic Mycoses

Challenges and Perspectives of Therapeutic Antibodies to Fungal Infections

Methods

Findings