Evaluation of DNA Vaccine Candidates against Foot-and-Mouth Disease Virus in Cattle

Michael Puckette; Benjamin A Clark; José Barrera; John G Neilan; Max V Rasmussen

doi:10.3390/vaccines11020386

Evaluation of DNA Vaccine Candidates against Foot-and-Mouth Disease Virus in Cattle

Vaccines (Basel). 2023 Feb 7;11(2):386. doi: 10.3390/vaccines11020386.

Authors

Michael Puckette¹, Benjamin A Clark², José Barrera³, John G Neilan¹, Max V Rasmussen¹

Affiliations

¹ U.S. Department of Homeland Security Science and Technology Directorate, Plum Island Animal Disease Center, P.O. Box 848, Greenport, NY 11944, USA.
² Oak Ridge Institute for Science and Education, Plum Island Animal Disease Center Research Participation Program, P.O. Box 848, Greenport, NY 11944, USA.
³ Leidos, Plum Island Animal Disease Center, P.O. Box 848, Greenport, NY 11944, USA.

Abstract

We evaluated four DNA vaccine candidates for their ability to produce virus-like particles (VLPs) and elicit a protective immune response against Foot-and-mouth disease virus (FMDV) in cattle. Two traditional DNA plasmids and two DNA minicircle constructs were evaluated. Both the pTarget O1P1-3C plasmid and O1P1-3C minicircle encoded a wild-type FMDV 3C protease to process the P1-2A polypeptide, whereas the O1P1-HIV-3C^T minicircle used an HIV-1 ribosomal frameshift to down-regulate expression of a mutant 3C protease. A modified pTarget plasmid with a reduced backbone size, mpTarget O1P1-3C^LT, used a 3C protease containing two mutations reported to enhance expression. All constructs produced mature FMDV P1 cleavage products in transfected cells, as seen by western blot analysis. Three constructs, O1P1-3C minicircles, pTarget O1P1-3C, and mpTarget O1P1-3C^LT plasmids, produced intracellular VLP crystalline arrays detected by electron microscopy. Despite VLP formation in vitro, none of the DNA vaccine candidates elicited protection from clinical disease when administered independently. Administration of pTarget O1P1-3C plasmid enhanced neutralizing antibody titers when used as a priming dose prior to administration of a conditionally licensed adenovirus-vectored FMD vaccine. Further work is needed to develop these DNA plasmid-based constructs into standalone FMD vaccines in cattle.

Keywords: DNA; cattle; foot-and-mouth disease virus; in vivo; minicircle; plasmid; vaccine.

Abstract

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