Abstract
Following the SARS-CoV-2 pandemic, several clinical trials have been approved for the investigation of the possible use of mAbs, supporting the potential of this technology as a therapeutic approach for infectious diseases. The first monoclonal antibody (mAb), Muromonab CD3, was introduced for the prevention of kidney transplant rejection more than 30 years ago; since then more than 100 mAbs have been approved for therapeutic purposes. Nonetheless, only four mAbs are currently employed for infectious diseases: Palivizumab, for the prevention of respiratory syncytial virus (RSV) infections, Raxibacumab and Obiltoxaximab, for the prophylaxis and treatment against anthrax toxin and Bezlotoxumab, for the prevention of Clostridium difficile recurrence. Protozoan infections are often neglected diseases for which effective and safe chemotherapies are generally missing. In this context, drug resistance and drug toxicity are two crucial problems. The recent advances in bioinformatics, parasite genomics, and biochemistry methodologies are contributing to better understand parasite biology, which is essential to guide the development of new therapies. In this review, we present the efforts that are being made in the evaluation of mAbs for the prevention or treatment of leishmaniasis, Chagas disease, malaria, and toxoplasmosis. Particular emphasis will be placed on the potential strengths and weaknesses of biological treatments in the control of these protozoan diseases that are still affecting hundreds of thousands of people worldwide.
Highlights
The in vitro production of murine monoclonal antibodies was first described in 1975 by Kohler and Milstein, a discovery that earned them the Nobel Prize in 1985 and that revolutionized the clinical practice and biomedical research [1,2,3]
A different monoclonal antibody (mAb) against CD25 was shown to reduce parasitemia and to increase effector memory T cells and IFN-γ/tumor necrosis factor α (TNF-α)-secreting cells in mice when administered during the acute phase, while when administered at the beginning of the chronic phase it was shown to reduce the local inflammatory process in the heart. These results indicate a potential for antiCD25 mAbs for the treatment of chronic Chagas disease (CD) and pave the way for more in depth investigations [23]
47D11, a human mAb that binds to cells expressing the viral spike protein, was shown to neutralize SARS-CoV-2 in vitro [127]
Summary
The in vitro production of murine monoclonal antibodies (mAbs) was first described in 1975 by Kohler and Milstein, a discovery that earned them the Nobel Prize in 1985 and that revolutionized the clinical practice and biomedical research [1,2,3]. The main advantages of this type of approach are (i) the possibility of exploiting drug repurposing, using drugs already developed, tested in clinical trials, and approved; (ii) the therapeutic efficacy is not undermined by the development of resistance or by antigenic variability; (iii) they might be found useful during chronic infections in which the host response contributes to the pathology. This strategy requires an in-depth knowledge of the mechanisms of host-pathogen interaction and of immunomodulation, which in the vast majority of the cases are far from being deciphered. Despite the role of the axis PD-1/PD-L1during Leishmania spp. infection is still unclear [53], it is known that the differentiation into M2 generates a favorable environment for amastigote survival while the differentiation into M1 leads to parasite death
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