|FABURAY, BONTO - Kansas State University|
|MOROZOV, IGOR - Kansas State University|
|RICHT, JUERGEN - Kansas State University|
Submitted to: Symposium Proceedings
Publication Type: Proceedings
Publication Acceptance Date: 8/1/2014
Publication Date: 8/18/2014
Citation: Mcvey, D.S., Wilson, W.C., Faburay, B., Morozov, I., Richt, J.A. 2014. Utility of Antibody Avidity for Rift Valley Fever Virus Vaccine Potency and Immunogenicity Studies. Symposium Proceedings. Bioprocessing Summit, 8/18-22/2014 in Boston, MA.
Interpretive Summary: This study characterizes the ability of antibodies derived from infection or vaccination in calves and mice with Rift Valley fever virus. Antibody responses were measured by multiple assays including serum neutralization. The strength of antibody binding (avidity) was determined in an ELISA using a recombinant Gn protein derived from the virus. In immunized mice, increasing avidity was associated with increasing neutralization antibody activity. This response was dose dependent, as vaccine potency increased, so did neutralization titers and Gn-binding avidity. Similar results were observed with both Np and NSs recombinant protein antigens. Further, similar responses were observed in calves and lambs immunized with MP-12 RVFV. These avidity-based assays could be used as correlates of neutralization responses and possibly functional immunity for clinical and laboratory testing of the immunological response properties of RVFV vaccines.
Technical Abstract: Disease outbreaks caused by arthropod-borne animal viruses (arboviruses) resulting in significant livestock and economic losses world-wide appear to be increasing. Rift Valley fever (RVF) virus is an important arbovirus that causes lethal disease in cattle, camels, sheep and goats in sub-Saharan Africa. There is concern that this virus could spread because of global warming, increased animal trade or through bioterrorism. There is a need to develop effective vaccines as well as robust analytical assays to support development and manufacturing of the vaccines. This study characterizes the avidity of antibody responses to RVFV MP-12 in calves and mice. Antibody responses were characterized by multiple ELISA’s and by serum neutralization. Avidity estimates were determined in an ELISA using a recombinant Gn protein expressed in baculovirus that employed multiple washes with chaotropic detergents. In immunized mice, increasing avidity correlated well (r>0.95) with increasing neutralization antibody activity. This response was dose dependent, as vaccine potency increased (increasing TCID50), so did neutralization titers and Gn-binding avidity. Similar results were observed with both Np and NSs recombinant protein antigens, but response kinetics differed from neutralization or anti-Gn activity. Further, similar responses were observed in calves and lambs immunized with MP-12 RVFV. These avidity-based ELISA’s could be used as correlates of neutralization responses for efficacy, in vivo potency and immunogenicity testing of experimental formulations of RVFV vaccines.