Monoclonal antibodies for the prevention of rabies: theory and clinical practice

Abstract

Monoclonal antibodies (MAbs) have become a unique and attractive class of biologics, possessing several desirable characteristics for use in human medicine. Anti-infective MAbs for several medically important viral agents, including rabies virus (RABV), have been developed and are currently at different stages of clinical development. Rabies is a vaccinepreventable but neglected zoonosis. After severe bite exposures, prompt administration of a combination of potent rabies vaccine and rabies immunoglobulin (RIG) is recommended. Due in part to cost, equine RIG has been largely used instead of human RIG, especially in the developing world. With an estimated 10 million RABV exposures annually, the use of MAbs has emerged in concept as a potential alternative to polyclonal RIG for future prophylaxis needs. Murine MAbs, although efficacious, are less attractive because of immunogenicity. However, human MAbs seem to have the potential to replace polyclonal RIG because they possess all the desirable characteristics for an intended biologic. The exquisite specificity of the MAbs for a single epitope is generally believed to result in narrow spectrum of RABV neutralization and perceived generation of escape mutants. These issues can be mitigated by formulating a cocktail of candidate MAbs that are directed against distinct, nonoverlapping epitopes. Expression of recombinant human MAbs in mammalian cell lines, such as Chinese hamster ovary and human retinal, is central to the economical production at an industrial scale. Thus far, human MAbs developed by two companies have successfully passed through Phase I or II clinical trials in countries such as the US and India.

mRNA mediates passive vaccination against infectious agents, toxins, and tumors

“…Antibody therapies were revolutionized by the development of the hybridoma technology for the production of monoclonal antibodies (mAbs) (Kohler & Milstein, 1975). Since then, more than thirty mAbs have been licensed, but only three of these mAbs are for infectious disease indications, respiratory syncytial virus, anthrax, and very recently rabies in India (Nagarajan et al, 2014). Nevertheless, there is ample evidence that it is possible to generate protective mAbs against many viruses and microorganisms (Teitelbaum et al, 1998;Nosanchuk et al, 2003;Both et al, 2013).…”

Generation of Arctic-like Rabies Viruses Containing Chimeric Glycoproteins Enables Serological Potency Studies

“…Here we tested four mAbs, RVC20 and CR57, and RVC58 and CR4098, which target antigenic site I and III respectively of the RABV G (Bakker et al, 2005; De Benedictis et al, 2016; Marissen et al, 2005). In order to meet WHO guidelines, which suggest RABV PEP should contain at least two antibodies to lower the probability of immune escape, CR57 and CR4098 have been combined into the CL184 mAb cocktail and undergone phase II clinical trials (Bakker et al, 2008; Nagarajan et al, 2014; WHO, 2013). In this study, each mAb effectively neutralised the AL RABV isolates, which can further serve as an indication that both antigenic sites are highly conserved across the AL RABV lineage.…”

The sero-epidemiology of infectious mononucleosis in Neyshabur, Northeast Iran during 2010–2014

“…very little emphasis is noted upon the investigation of humoral immunity during primary infection and defects in antibody level could contribute to the severity of the disease burden during acute IM [11]. The virus can persistently shed in saliva for duration of 6 months [12].…”