Recombinant chimeric horsepox virus (TNX-801) is attenuated relative to vaccinia virus strains in both in vitro and in vivo models

• Published in: mSphere Vol. 9; no. 12; p. e0026524
• Main Authors: Trefry, Stephanie V., Awasthi, Mayanka, Raney, Christy N., Cregger, Amy L., Gonzales, Chase A., Layton, Brittney L., Enamorado, Robert N., Martinez, Nelson A., Gohegan, Deborah S., Masoud-Bahnamiri, Masoudeh, Cho, Jennifer Y., Myscofski, Dawn M., Moulaei, Tinoush, Ziółkowska, Natasza E., Goebel, Scott J., Lederman, Seth, Bavari, Sina, Nasar, Farooq
• Format: Journal Article
• Language: English
• Published: United States American Society for Microbiology 19.12.2024
• Subjects: Animals; Biotechnology; Cell Line; Chlorocebus aethiops; Disease Models, Animal; Editor’s Pick; Female; Fowlpox virus - genetics; Fowlpox virus - immunology; horsepox; human primary cells; Humans; immunocompromised mice; Mice; Orthopoxvirus; Research Article; Smallpox - immunology; Smallpox - prevention & control; Smallpox Vaccine - genetics; Smallpox Vaccine - immunology; Vaccines, Attenuated - administration & dosage; Vaccines, Attenuated - genetics; Vaccines, Attenuated - immunology; vaccinia; Vaccinia virus - genetics; Vaccinia virus - immunology; Vero Cells; Virus Replication - drug effects; immunocompromised mice; human primary cells; vaccinia; Orthopoxvirus; horsepox
• ISSN: 2379-5042; 2379-5042
• DOI: 10.1128/msphere.00265-24

Variola and monkeypox viruses are medically important pathogens that can cause fatal human disease. The two FDA-approved vaccines, ACAM-2000 and JYNNEOS, have important advantages and disadvantages. ACAM-2000 offers durable immunity; however, it has high adverse event rates. In contrast, JYNNEOS has a safer profile but requires two doses 4-weeks apart to achieve comparable immunity. Consequently, there is a need for vaccines offering durable immunity via single immunization with minimal adverse events. TNX-801 is a preclinical stage vaccine that can stimulate potent immunity via a single dose and provides protection against lethal mpox disease in the nonhuman primate model. Here, we show that TNX-801 is >10- to 1,000-fold attenuated in in vitro and in vivo models including human primary cells and immunocompromised murine models than vaccine strains utilized in smallpox eradication. The natural attenuation of TNX-801 and its ability to induce protective immunity via a single vaccination are promising and warrants further development.