Chicken recombinant antibodies against infectious bursal disease virus are able to form antibody–virus immune complex

Abstract

Virus particles exposed to specific anti-virus antibodies result in the formation of immune complexes (Icx). Recent vaccination strategies have employed this feature, and an infectious bursal disease virus (IBDV) vaccine based on Icx has been released and is expected to replace conventional IBDV vaccines. We evaluated whether chicken recombinant antibodies (rAb) specific for IBDV, rather than conventional chicken anti-IBDV sera, could be used to generate Icx. Out of 14 rAb expressed as soluble single-chain variable fragments (scFv), nine were able to completely neutralize Bursavac, a live IBDV vaccine, when tested in ovo. When these rAb were mixed with IBDV and inoculated into either 18-day-old embryos, or 1-day-old or 2-week-old specific pathogen free chicks, a rAb.IBDV complex was formed. These Icx were similar to those produced by polyclonal chick anti-IBDV sera and IBDV. Following inoculation of the rAb.IBDV complex, the virus was rendered non-infectious for 5 to 7 days. After this time virus was released from the Icx, resulting in infection of the inoculated chicks and subsequent induction of an immune response and protection against virulent IBDV challenge. The results indicated that genetically derived antibodies can replace polyclonal sera in the formulation of Icx vaccines.

Antibody fragments, expressed by a fowl adenovirus vector, are able to neutralize infectious bursal disease virus

“…In previous studies, the core scFv has been able to neutralize IBDV effectively in ovo (Ignjatovic et al, 2006). As a pre-requisite to a possible in ovo-based vaccine trial, we tested the ability of our FAdV-produced secreted scFv and scFv-Fc to protect embryonated eggs from IBDV infection (Table 3).…”

“…As a pre-requisite to a possible in ovo-based vaccine trial, we tested the ability of our FAdV-produced secreted scFv and scFv-Fc to protect embryonated eggs from IBDV infection (Table 3). This was conducted using an immune complex simulation on SPF ED 10 embryos as outlined by Ignjatovic et al (2006). In this simulation, the antibody protects the embryo by binding and retaining the virus in the complex, and thus preventing its release and subsequent infection of the embryo.…”

“…Analyses of hatch rate, survival and bursa:body weight ratios, as well as viral release from the complex, would be conducted to scrutinize the vaccine mechanism and to look for protection. Our ultimate aim is to see if our scFv-Fc antibody fragment can function as an immune complex vaccine in a similar way demonstrated for the scFv (Ignjatovic et al, 2006) and can eventually replace chicken immune serum.…”

“…Cell-culture adapted IBDV strain GT-101 (Fahey et al, 1991) was used for in vitro neutralization assays. BursaVac IBDV vaccine strain V877 (Ignjatovic et al, 2006) was used for in ovo neutralization assays.…”

“…Anti-viral scFv have been used to neutralize a wide range of animal viruses in vivo including infectious bursal disease virus (IBDV) (Ignjatovic et al, 2006), severe acute respiratory syndrome virus (Sui et al, 2004), rabies virus (Muller et al, 1997;Ray et al, 2001;Kramer et al, 2005), canine parvovirus (Yuan & Parrish, 2000) and western equine encephalitis virus (Long et al, 2001). It is also possible to engineer proteins onto the C terminus of scFv such as the immunoglobulin Fc domain (scFv-Fc), to confer greater stability and prolonged in vivo persistence (Powers et al, 2001;Borsi et al, 2002;Ono et al, 2003).…”