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Title: Novel 6xHis tagged foot-and-mouth disease virus vaccine bound to nanolipoprotein adjuvant via metal ions provides antigenic distinction and effective protective immunity

item RAI, DEVENDRA - University Of Connecticut
item DAIZ-SAN SEGUNDO, FAYNA - University Of Connecticut
item Schafer, Elizabeth
item BURRAGE, THOMAS - Us Deparment Of Homeland Security
item Rodriguez, Luis
item De Los Santos, Teresa
item HOEPRICH, PAUL - Lawrence Livermore National Laboratory
item Rieder, Aida - Elizabeth

Submitted to: Virology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 4/25/2016
Publication Date: 4/27/2016
Citation: Rai, D., Daiz-San Segundo, F., Schafer, E.A., Burrage, T., Rodriguez, L.L., De Los Santos, T.B., Hoeprich, P.D., Rieder, A.E. 2016. Novel 6xHis tagged Foot-and-Mouth Disease Virus vaccine bound to nanolipoprotein adjuvant via metal ions provides antigenic distinction and effective protective immunity. Virology. 495:136-147. doi: 10.1016/j.virol.2016.04.027.

Interpretive Summary: Foot-and-mouth disease virus (FMDV) is the cause of a devastating disease of cattle and other cloven-hoofed animals that is responsible for millions of dollars in losses around the globe each year, prompting researchers in both the U.S. and other countries to develop more effective vaccines In this study, we describe an innovative approach to produce marker FMDV that bind metals and by mean of this new property, their purification is facilitated. More importantly, by mixing the marker virus with a nanolipid adjuvant we produced an efficacious vaccine that induced protective immunity. This novel technology could be used to prepare marker vaccines to other FMDV serotypes or be applied on vaccine developments against other relevant pathogens of human and animals.

Technical Abstract: Here, we engineered two FMD viruses and histidine residues inserted into or fused to the FMDV capsid. Both 6xHis viruses exhibited growth kinetics, plaque morphologies and antigenic characteristics similar to wild-type virus. The 6xHis tag allowed one-step purification of the mutant virions by Co2 affinity columns. Electron microscopy and biochemical assays showed that the 6xHis FMDVs readily assembled into antigen; adjuvant complexes in solution, by conjugating with Ni2+ -checelated nanolipoprotein and monophosphoryl lipid A adjuvant (MPLA:NiNLP). Animals immunized with the inactivated 6xHis-FMDV: MPLA:NiNLP vaccine acquired enhanced protective immunity against FMDV challenge compared to virions alone. Induction of anti-6xHis and anti-FMDV neutralizing antibodies in the immunized animals could be exploited in the differentiation of vaccinated from infected animals needed for the improvement of FMD control measures. The novel marker vaccine/nanolipid technology described here has broad applications for the development of distinctive and effective immune responses to other pathogens of importance.