An FDA-sanctioned vaccine for smallpox and mpox is effective but can result in side effects. The alternative option requires several doses. A new experimental vaccine only needs a single dose and utilizes the horsepox virus to combine the advantages of both methods.
Vaccines for smallpox and mpox come in two main types. One type involves a single administration of a live virus, which poses a risk of serious side effects; the other is a newer option created with a replication-deficient virus that comes with fewer side effects but necessitates two doses. A new vaccine currently being developed at Tonix Pharmaceuticals in Frederick, Maryland, seeks to merge the strengths of both approaches by employing the horsepox virus as a safe alternative to deliver the benefits of a multi-dose vaccine in just one shot.
This week in mSphere, researchers from Tonix Pharmaceuticals presented findings indicating that the horsepox virus used in the experimental vaccine is significantly more attenuated and less likely to cause a widespread infection compared to the vaccinia virus, which is the basis of the FDA-approved single-dose vaccine.
“Our goal is to achieve the robust immunity of older vaccines while maintaining the safety profile of newer ones, and the preliminary data is quite promising,” stated virologist Farooq Nasar, Ph.D., a senior author of the study. “We aim to find a balance.”
Smallpox, caused by the variola virus, was an extremely contagious disease with a death rate ranging from 30% to 97%. Historical evidence suggests it has been infecting humans for millennia, and the World Health Organization (WHO) estimated that smallpox claimed between 300 and 500 million lives in the 20th century. An effective vaccination campaign initiated in the 1950s ended its spread, leading the WHO to declare the disease eradicated in 1980.
Mpox, formerly known as monkeypox, is a related illness caused by the monkeypox virus, which, like variola, belongs to the genus Orthopoxvirus. Since 2022, there have been several mpox outbreaks, with case fatality rates estimated between 0.2% and 11%. The two FDA-approved smallpox vaccines are also authorized for preventing mpox infections.
The FDA-approved live-virus smallpox vaccine includes the vaccinia virus, a milder relative of the Orthopoxvirus family, which helps the immune system develop defenses against the smallpox infection. Interestingly, researchers discovered a few years ago that smallpox vaccines administered before and during the American Civil War contained a virus that was over 99% genetically akin to horsepox — another member of the Orthopoxvirus family. This finding spurred research into whether a vaccine utilizing live, weakened horsepox could provide immunity without the undesirable side effects associated with the live vaccinia virus-based vaccine.
Previous investigations by Tonix Pharmaceuticals and other groups highlighted that the experimental vaccine elicited an antibody response without causing illness in non-human primates; moreover, it effectively protected them from a lethal dose of the monkeypox virus without any clinical symptoms.
The latest research by virologists Nasar and Stefanie Trefry, Ph.D., builds upon these earlier findings. Their study, which tested both human cell lines and mouse models, compared the replication of viruses in those treated with vaccinia virus strains to those given the novel horsepox virus.
The results showed that the horsepox virus is up to 1,000 times more attenuated than the vaccinia virus strains, indicating it has a significantly lower level of infectious particles. Attenuation reduces a virus’s potency, making it less probable to incite a systemic infection in the host. Mice receiving the vaccinia-based vaccines frequently exhibited severe symptoms, while those administered the experimental horsepox vaccine showed no negative effects.
The researchers are preparing to launch phase I human clinical trials to assess the vaccine’s safety in people. Currently, smallpox exists only in labs in the U.S. and Russia, and research efforts are ongoing to explore smallpox vaccines as a potential defense against it being used as a bioterrorism weapon. However, according to Nasar, addressing future mpox outbreaks is a more immediate public health priority. This new vaccine aspires to tackle both challenges.
“We are dedicated to developing a product that can combat both mpox and smallpox,” he stated.
