Human monoclonal antibodies as candidate therapeutics against emerging viruses

Abstract

The emergence of new pathogens, such as severe acute respiratory syndrome coronavirus (SARS-CoV), Middle East respiratory syndrome coronavirus (MERS-CoV), and Ebola virus, poses serious challenges to global public health and highlights the urgent need for novel antiviral approaches. Monoclonal antibodies (mAbs) have been successfully used to treat various diseases, particularly cancer and immunological disorders. Antigen-specific mAbs have been isolated using several different approaches, including hybridoma, transgenic mice, phage display, yeast display, and single B-cell isolation. Consequently, an increasing number of mAbs, which exhibit high potency against emerging viruses in vitro and in animal models of infection, have been developed. In this paper, we summarize historical trends and recent developments in mAb discovery, compare the advantages and disadvantages of various approaches to mAb production, and discuss the potential use of such strategies for the development of antivirals against emerging diseases. We also review the application of recently developed human mAbs against SARS-CoV, MERS-CoV, and Ebola virus and discuss prospects for the development of mAbs as therapeutic agents against emerging viral diseases.

Coronaviruses: a paradigm of new emerging zoonotic diseases

“…Many monoclonal antibodies neutralizing SARS-CoV and MERS-CoV infections have been identified, and some of them displayed a potent inhibitory effect in in vitro and in vivo experiments. In fact, it has been shown that antibody administration fully protected mice from viral challenges (Jin et al 2017). Thus, as reported for Ebola virus, the use of monoclonal antibodies to treat severe CoVs infections could be a promising strategy (Jin et al 2017).…”

“…In fact, it has been shown that antibody administration fully protected mice from viral challenges (Jin et al 2017). Thus, as reported for Ebola virus, the use of monoclonal antibodies to treat severe CoVs infections could be a promising strategy (Jin et al 2017).…”

Engineering a Novel Antibody-Peptide Bispecific Fusion Protein Against MERS-CoV

“…Monoclonal antibodies represent one of the most promising immunotherapeutic agents for the treatment of cancers and infectious diseases [7,[47][48][49][50][51][52]. Previously, we used RBD of MERS-CoV S protein to screen a non-immune phage-displayed Fab library and identified a highly potent human neutralizing mAb m336 and a panel of other mAbs against MERS-CoV [34,36,37].…”

“…In recent years, tremendous efforts have been made in the engineering of bispecific or multi-specific antibodies by combining two or more functional antigen-recognizing elements into a single construct [5,6]. Such novel antibodies, or antibody-based fusion proteins, could be particularly beneficial for the treatment of viral infections, which typically require potent and multi-functional therapeutics to prevent the frequent incidence of viral escape mutants [7]. For instance, we previously engineered a bispecific and multivalent anti-HIV-1 fusion protein, by incorporating the HIV-1 neutralizing antibody and the engineered single-domain CD4 into a single antibody-like molecule,…”

A novel luciferase immunosorbent assay performs better than a commercial enzyme-linked immunosorbent assay to detect MERS-CoV specific IgG in humans and animals

“…MERS-CoV poses a significant threat to public health worldwide because of the high fatality rate of MERS infection and potential outbreaks of MERS-CoV infection in healthcare facilities. Furthermore, there are no specific vaccines or therapeutics for the prevention or treatment of MERS-CoV infection [15][16][17][18][19][20][21].…”