Recombinant chimeric Horsepox Virus (TNX-801) is attenuated relative to Vaccinia Virus Strains in Human Primary Cell Lines and in Immunocompromised Mice

Abstract

Recombinant chimeric Horsepox virus (TNX-801) is a preclinical vaccine in development against Monkeypox and smallpox. In this brief report, we investigated the potential phenotypic differences in in vitro and in vivo models between TNX-801 and older VACV-based vaccine strains (VACV-IHD, VACV-Lis, VACV-NYC) used in the eradication of smallpox virus. TNX-801 displayed a small plaque phenotype (∼1-2 mm) in both BSC-40 and Vero-E6 cells and yielded >10- to 100-fold lower infectious titers than the VACV strains in multiple-step replication kinetics. Growth kinetics in primary human cell lines from two main routes of poxvirus transmission, respiratory and dermal tracts, yielded ∼10- to 119-fold lower infectious titers of TNX-801. Intranasal infection of immunocompromised mice (C56BL/6 Ifnar^−/−/Ifngr^−/−) with VACV strains at 6.0 and 5.0 log₁₀ PFU produced uniform lethal disease. In contrast, TNX-801 at 8.0 log₁₀ PFU was unable to produce any clinical disease in mice. These data demonstrate that TNX-801 is >10- to 1,000-fold more attenuated than older VACV-based smallpox vaccines in human primary cell lines and immunocompromised mice.