Development of Therapeutic Monoclonal Antibodies for Emerging Arbovirus Infections

Abstract

Antibody-based passive immunotherapy has been used effectively in the treatment and prophylaxis of infectious diseases. Outbreaks of emerging viral infections from arthropod-borne viruses (arboviruses) represent a global public health problem due to their rapid spread, urging measures and the treatment of infected individuals to combat them. Preparedness in advances in developing antivirals and relevant epidemiological studies protect us from damage and losses. Immunotherapy based on monoclonal antibodies (mAbs) has been shown to be very specific in combating infectious diseases and various other illnesses. Recent advances in mAb discovery techniques have allowed the development and approval of a wide number of therapeutic mAbs. This review focuses on the technological approaches available to select neutralizing mAbs for emerging arbovirus infections and the next-generation strategies to obtain highly effective and potent mAbs. The characteristics of mAbs developed as prophylactic and therapeutic antiviral agents for dengue, Zika, chikungunya, West Nile and tick-borne encephalitis virus are presented, as well as the protective effect demonstrated in animal model studies.

Keywords: alphavirus; antibody discovery; arbovirus; flavivirus; monoclonal antibody; neutralizing antibody.

Figure 2

Schematic representation of the polypeptides encoded by flavivirus (a) and alphavirus (b) genomes adapted from Pierson and Diamond 2020 [61] and Rupp et al. [65], respectively. (a) Flavivirus genome has a single open reading frame (ORF) and encodes three structural proteins, capsid (C), pre-membrane (pr) and envelope (E), followed by seven nonstructural proteins (NS1, NS2A, NS2B, NS3, NS4A, NS4B and NS5). 2K: domain between NS4A and NS4B. (b) Alphavirus genome has two ORFs. The first ORF translates four nonstructural proteins (nsP1, nsP2, nsP3 and nsP4) from genomic RNA, while the second ORF encodes five structural proteins (capsid, E3, E2, 6K/TF and E1) through a subgenomic mRNA. 5′ subgenomic UTR: a third UTR between two ORFs.

Figure 1

Technologies for mAb discovery. (A) Hybridoma. (B) Antibody humanization. (C) In vitro display technology. (D) B-cell sorting technology.