Abstract
Today there are many licensed antiviral drugs, but the emergence of drug resistant strains sometimes invalidates the effects of the current therapies used in the treatment of infectious diseases. Compared to conventional antiviral drugs, monoclonal antibodies (mAbs) used as pharmacological molecules have particular physical characteristics and modes of action, and, therefore, they should be considered as a distinct therapeutic class. Despite being historically validated, antibodies may represent a novel tool for combatting infectious diseases. The current high cost of mAbs' production, storage and administration (by injection only) and the consequent obstacles to development are outweighed by mAbs' clinical advantages. These are related to a low toxicity combined with high specificity and versatility, which allows a specific antibody to mediate various biological effects, ranging from the virus neutralization mechanisms to the modulation of immune responses.This review briefly summarizes the recent technological advances in the field of immunoglobulin research, and the current status of mAb-based drugs in clinical trials for HIV and HCV diseases. For each clinical trial the available data are reported and the emerging conceptual problems of the employed mAbs are highlighted.This overview helps to give a clear picture of the efficacy and challenges of the mAbs in the field of these two infectious diseases which have such a global impact.
Highlights
The innate immune response is the first-line defense in determining the outcome of an infection
In this review we focus on the monoclonal antibodies (mAbs)-therapies underway in clinical trials (Table 1) designed for human immunodeficiency virus (HIV) and hepatitis C virus (HCV) infectious diseases
In the context of HIV disease, despite intensive study over two decades, only a small number of broadly neutralizing mAbs have been identified from infected patients and little is known about their activity in vivo
Summary
The innate immune response is the first-line defense in determining the outcome of an infection. In the context of HIV disease, despite intensive study over two decades, only a small number of broadly neutralizing mAbs have been identified from infected patients and little is known about their activity in vivo These antibodies are able to inhibit viral entry of most primary HIV isolates in vitro [17,62,63,64] and the exceptionally high level of mutation found in their genes may reflect chronic immune responses to HIV and persistent hypermutation and selection [65]. The PD-1:PD-L1 pathway delivers inhibitory signals which regulate T cell activation As a result it performs a key role in various processes, namely in multiple tolerance checkpoints that prevent autoimmunity, in the suppressive tumor microenvironment, in the immune-mediated tissue damage, in host defenses aimed at eradicating microbial pathogens and tumors and in T cell exhaustion that contributes to both lack of viral control during chronic infections and to T cell unresponsiveness [105]. Because the host mechanisms that inhibit T cell activity are common and conserved aside from specific virus-encoded immune evasion strategies, the antibodies targeting inhibitory receptors may prove extremely versatile drugs potentially effective against multiple classes of viruses
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