Antibody-based therapeutic interventions: possible strategy to counter chikungunya viral infection

Abstract

Chikungunya virus (CHIKV), a mosquito-transmitted disease that belongs to the genus Alphaviruses, has been emerged as an epidemic threat over the last two decades, and the recent co-emergence of this virus along with other circulating arboviruses and comorbidities has influenced atypical mortality rate up to 10%. Genetic variation in the virus has resulted in its adaptability towards the new vector Aedes albopictus other than Aedes aegypti, which has widen the horizon of distribution towards nontropical and non-endemic areas. As of now, no licensed vaccines or therapies are available against CHIKV; the treatment regimens for CHIKV are mostly symptomatic, based on the clinical manifestations. Development of small molecule drugs and neutralizing antibodies are potential alternatives of worth investigating until an efficient or safe vaccine is approved. Neutralizing antibodies play an important role in antiviral immunity, and their presence is a hallmark of viral infection. In this review, we describe prospects for effective vaccines and highlight importance of neutralizing antibody-based therapeutic and prophylactic applications to combat CHIKV infections. We further discuss about the progress made towards CHIKV therapeutic interventions as well as challenges and limitation associated with the vaccine development. Furthermore this review describes the lesson learned from chikungunya natural infection, which could help in better understanding for future development of antibody-based therapeutic measures.

A molecular understanding of alphavirus entry

“…These include neutralizing monoclonal antibodies that block attachment, internalization, and pH-dependent fusion [105][106][107]. Monoclonal antibodies can be developed quickly during epidemics [107], have a rapid onset of protection [107], and facilitate viral clearance through multiple mechanisms including direct neutralization of virus [108] and indirect antibody-dependent effector functions including cell-mediated cytotoxicity [107,109], complement-dependent cytotoxicity, and phagocytosis [107]. A phase I/II clinical trial (NCT02230163) was initiated to determine the safety and efficacy of anti-CHIKV hyperimmune sera for treating neonatal infections resulting from vertical CHIKV transmission [110].…”

“…Monoclonal antibodies [107]; curcumin [116] Co-protoporphyrin IX and Sn-protoporphyrin IX [120] Suramin [114,115,118,[142][143][144] Block receptor binding, ADCC; CDC Engage in hydrophobic interactions in the lipid bilayer to disrupt envelope integrity E1/E2 heterotrimer, may disrupt heterodimer assembly 2. Clathrin-mediated endocytosis Pitstop [145] Clathrin inhibitor 3.…”

Identification of an anti–SARS–CoV-2 receptor-binding domain–directed human monoclonal antibody from a naïve semisynthetic library

“…The antibodies can work via two different mechanisms, i.e. by direct neutralization of target viral antigen and also by indirect effector mechanisms such as antibody-dependent cell-mediated cytotoxicity and complement-dependent cytotoxicity, wherein antibody binds to infected cells and potentially clears the viral reservoirs ( 2 , 3 ).…”

Hybridoma technology a versatile method for isolation of monoclonal antibodies, its applicability across species, limitations, advancement and future perspectives

“…In HIV-1, researchers are working to develop broadly neutralizing antibodies targeting conformational epitopes [120]. Similar approaches have been taken for other viral antigenic targets [121]. In many of these viral infections "conventional Abs" are generated in response to virus infection, but the virus adopts numerous evasion strategies like conformational masking of antigenic targets by glycosylation, high mutation rate etc.…”