Tonix Pharmaceuticals Identifies Three New Murine Models for Mpox, Reveals 2022 Clade IIb Is Up to 100,000-Fold Less Virulent Than 2003 Clade IIa
核心洞察
Tonix Pharmaceuticals (搜索) published research in the Journal of Virology identifying three new murine models susceptible to mpox (搜索) clade II infection, addressing a critical gap in small animal models for mpox research.
The study demonstrates that the 2022 outbreak clade IIb is 100 to 100,000-fold less virulent than the historic 2003 clade IIa, which may explain its rapid global spread through subclinical infections.
Tonix is advancing TNX-801, a live attenuated horsepox-based vaccine candidate, with a Phase 1 trial expected in 2027 pending FDA clearance of an IND application.
Tonix Pharmaceuticals (搜索) Holding Corp. announced on July 15, 2026, the publication of a study in the Journal of Virology that identifies three new murine models for investigating mpox (搜索) pathogenesis and reveals striking differences in virulence between mpox clades. The research, conducted entirely at Tonix's facilities, demonstrates that the clade IIb strain from the 2022 global outbreak is 100 to 100,000-fold less virulent than the clade IIa strain from the 2003 U.S. outbreak.
The paper, titled "Monkeypox virus (搜索) clade IIb isolate exhibits reduced virulence relative to clade IIa isolates in multiple murine models," addresses a longstanding limitation in mpox (搜索) research: the lack of suitable small animal models for studying emerging viral subclades.
"The decreased virulence of clade IIb may have contributed to its ability to spread worldwide," said Sina Bavari, Ph.D., Executive Vice President of Tonix and site head of the company's Research and Development Center (RDC) in Frederick, Maryland. "Indolent subclinical infection is a risk factor for unintentional spread."
Three Novel Models Expand Research Capabilities
The study expands on the previously established CAST/EiJ mouse model by evaluating susceptibility to both MPXV subclade IIa and IIb infection in 7- to 8-week-old and 4- to 5-month-old mice. The demonstrated susceptibility of older CAST/EiJ mice to clade IIa infection highlights the utility of this model for evaluating long-term vaccine durability and protective efficacy.
In addition, the research describes three novel C57BL/6 mouse models deficient in the interferon-α receptor, interferon-γ receptor, or both receptors. Collectively, these models provide new tools for rapidly investigating the pathogenesis of emerging MPXV subclades and evaluating medical countermeasures, including vaccines.
"To examine the pathogenesis of emerging mpox (搜索) clades, we identified three new murine models susceptible to mpox clade II infection, which revealed significant differences in virulence between clades," said Seth Lederman, M.D., Chief Executive Officer of Tonix Pharmaceuticals (搜索).
Virulence Differences and Global Spread
Mpox (搜索) is caused by four distinct MPXV subclades—Ia, Ib, IIa, and IIb—which, despite genetic similarities, exhibit markedly different case fatality rates: Ia at approximately 11%, Ib and IIa at approximately 4%, and IIb at approximately 0.2%. Since 2022, multiple mpox outbreaks caused by the previously unrecognized Ib and IIb subclades have prompted the World Health Organization to declare two Public Health Emergencies of International Concern.
The research was led by Farooq Nasar, Ph.D., Director of Virology at Tonix, utilizing the company's state-of-the-art laboratory capabilities, including a Biosafety Level 3 (BSL-3) lab and an Animal Biosafety Level 3 (ABSL-3) facility at the RDC, located near the center of the U.S. biodefense research community.
TNX-801 Vaccine Development
Tonix is advancing TNX-801, a live, attenuated, minimally replicative investigational vaccine candidate based on horsepox virus, for the prevention of mpox (搜索) and smallpox. The vaccine is currently in pre-clinical development and is expected to enter a Phase 1 study in 2027, pending FDA clearance of an Investigational New Drug Application (IND). TNX-801 is in the pre-IND stages of development.
"Importantly, a deeper understanding of mpox (搜索) virus pathogenesis will help guide the continued development and positioning of the TNX-801 vaccine platform," said Bavari. "Tonix is committed to advancing the understanding of emerging mpox disease and to developing TNX-801 platform as a potential vaccine candidate to address the continuing global threat posed by mpox."
Ongoing Public Health Threat
Cases of mpox (搜索) are currently increasing in multiple regions of the Americas. While the WHO has lifted the PHEIC designation for both clade IIb and clade Ib, mpox continues to spread in Africa, and mutations of the virus are considered by public health experts to be an ongoing threat requiring monitoring for new epidemic spread. The clade II mpox affects mostly men who have sex with men in the U.S., where it has become endemic, while clade Ib affects both children and adults.
"Global mpox (搜索) outbreaks that have caused severe human disease continue to occur due to previously unrecognized subclades," Lederman added. "New approaches to understand and mitigate the spread of emerging mpox subclades are urgently needed."