In recent findings published in mSphere, researchers at Tonix Pharmaceuticals have unveiled promising data regarding the development of a new vaccine utilizing the horsepox virus. This experimental vaccine appears to be significantly more attenuated, meaning it is much less likely to cause systemic infection, compared to the vaccinia virus used in the currently approved single-dose smallpox vaccine by the U.S. Food and Drug Administration (FDA).
The principal investigator, virologist Dr. Farooq Nasar, emphasized the aim of achieving the potent immunity offered by traditional vaccines alongside the safety profile of contemporary ones. "We would like to be in the middle," he stated, expressing optimism about the initial data.
Smallpox, caused by the variola virus, had a devastating impact throughout history, with fatality rates ranging from 30% to 97%. It is estimated by the World Health Organization (WHO) that between 300-500 million people succumbed to the disease in the 20th century alone. However, a comprehensive vaccination program initiated in the 1950s culminated in the eradication of smallpox in 1980.
Another related disease, mpox, caused by the monkeypox virus, has seen multiple outbreaks since 2022, with case fatality rates varying from 0.2% to 11%. The two FDA-approved smallpox vaccines are also authorized for mpox prevention. They rely on the vaccinia virus, a less dangerous member of the Orthopoxvirus family, to trigger immunity against smallpox. Recently, researchers discovered that historical smallpox vaccines contained a virus almost identical to horsepox, sparking interest in a vaccine based on a live, attenuated horsepox virus to potentially avoid the side effects associated with the vaccinia-based vaccine.
Previous studies from Tonix Pharmaceuticals and other institutions demonstrated that the horsepox-based vaccine elicited an antibody response and provided protection in non-human primates against lethal monkeypox virus exposure without causing disease. Building upon these findings, Dr. Nasar and Dr. Stefanie Trefry have led a new study comparing the replication of vaccinia and horsepox viruses in human cell lines and mouse models. Their research showed that the horsepox virus is up to 1,000 times more attenuated than its vaccinia counterpart, containing far fewer infectious particles. Mice injected with vaccinia strains often experienced severe symptoms, while those vaccinated with horsepox did not show adverse effects.
With successful preliminary results, Tonix Pharmaceuticals is moving towards phase I human clinical trials to further assess the vaccine's safety. While smallpox now only exists in laboratories in the US and Russia, there's a continuous need to explore vaccination options as a precaution against its potential use as a bioterrorism agent. The immediate public health challenge, as noted by Dr. Nasar, is the prevention of future mpox outbreaks. The researchers are hopeful that their new vaccine could offer dual protection against both diseases. Dr. Nasar underscores the ongoing commitment, "We're focused on making a product that can be used against both mpox and smallpox."
