Author:
Trefry Stephanie V,Raney Christy N,Cregger Amy L,Gonzales Chase A,Layton Brittney L,Enamorado Robert N,Martinez Nelson A,Gohegan Deborah S,Moulaei Tinoush,Ziółkowska Natasza E,Goebel Scott J,Lederman Seth,Bavari Sina,Nasar Farooq
Abstract
AbstractRecombinant 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 inin vitroandin vivomodels 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/6Ifnar−/−/Ifngr−/−) with VACV strains at 6.0 and 5.0 log10PFU produced uniform lethal disease. In contrast, TNX-801 at 8.0 log10PFU 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.
Publisher
Cold Spring Harbor Laboratory
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