Safety and immunogenicity of orally administered poxvirus vectored constructs in the white-footed mouse (Peromyscus leucopus)

Jordan T Mandli; Susan M Paskewitz; Jorge E Osorio

doi:10.1016/j.jvacx.2022.100259

Safety and immunogenicity of orally administered poxvirus vectored constructs in the white-footed mouse (Peromyscus leucopus)

Vaccine X. 2022 Dec 28:13:100259. doi: 10.1016/j.jvacx.2022.100259. eCollection 2023 Apr.

Authors

Jordan T Mandli¹, Susan M Paskewitz², Jorge E Osorio¹

Affiliations

¹ University of Wisconsin - Madison, School of Veterinary Medicine, 1656, Linden Dr., Madison, WI 53706, USA.
² University of Wisconsin-Madison, Department of Entomology, College of Agricultural and Life Sciences, 1630, Linden Drive, Madison, WI 53706, USA.

Abstract

Globally, zoonotic spillover is becoming more frequent and represents a growing public health concern. Reservoir-targeted vaccination offers an intriguing alternative to traditional vaccine practices by establishing protection in wild populations that maintain the natural pathogen cycle. As an important pathogen reservoir, Peromyscus leucopus Rafinesque or the white-footed mouse has been the target of several experimental vaccines. However, strategies are limited by the method of administration, need for repeated dosing, or safety of constructs in the field. To address these concerns, we evaluated two highly attenuated poxviruses, raccoonpox virus (RCN) and modified vaccinia Ankara (MVA) virus as potential oral vaccine vectors in white-footed mice. Following oral administration, P. leucopus showed no adverse signs. A single oral dose elicited robust immune responses in mice to the foreign influenza hemagglutinin protein expressed by poxvirus vaccine vectors. Serum hemagglutinin inhibition antibody titers were detected by day 7 post immunization and persisted until study termination (77 days post immunization). This study establishes the safety and immunogenicity of recombinant MVA and RCN poxviruses in P. leucopus and demonstrates the suitability of these vectors as part of a reservoir-targeted vaccine strategy for white-footed mice.

Keywords: Hemagglutinin; Influenza; MVA, modified vaccinia Ankara; Modified vaccinia Ankara; RCN, Racoonpox virus; Raccoonpox virus; Vaccine; White-footed mouse.