Abstract
Chikungunya virus (CHIKV) is the most common alphavirus infecting humans worldwide. Antibodies play pivotal roles in the immune response to infection. Increasingly, therapeutic antibodies are becoming important for protection from pathogen infection for which neither vaccine nor treatment is available, such as CHIKV infection. The new generation of ultra-potent and/or broadly cross-reactive monoclonal antibodies (mAbs) provides new opportunities for intervention. In the past decade, several potent human and mouse anti-CHIKV mAbs were isolated and demonstrated to be protective in vivo. Mechanistic studies of these mAbs suggest that mAbs exert multiple modes of action cooperatively. Better understanding of these antiviral mechanisms for mAbs will help to optimize mAb therapies.
Highlights
Chikungunya virus (CHIKV) is an emerging alphavirus
CHIKV is transmitted to humans by Aedes species mosquitoes and causes an acute febrile illness accompanied by severe arthralgia, with relapses lasting up to several months and recurring for several years in up to 40% of patients [2]
Cryo-electron microscopy structure of mature alphavirus particles and virus-like particles (VLPs) revealed that virions are composed of two icosahedral layers: the outer envelope layer and the inner nucleocapsid (NC) core, both with T = 4 quasi-icosahedral symmetry
Summary
Spreading rapidly from endemic areas of Africa and Asia to Europe and the Americas, CHIKV is the most common alphavirus infecting humans globally [1]. In a 2007 outbreak in India, the median workdays lost due to CHIKV infection was 35 [3]. This is one reason why CHIKV is classified by NIAID as a biodefense priority pathogen, despite low fatality rates. Several potent human and mouse anti-CHIKV monoclonal antibodies (mAbs) were isolated and demonstrated to be protective in vivo [5,6,7,8,9,10,11,12,13]. We will discuss our understanding of the multiple antiviral mechanisms through which these mAbs exert viral inhibition
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