Recreation of horsepox vaccine sparks public outcry

Credit: Lisa Qian/Photo Editor Credit: Lisa Qian/Photo Editor

Last week, the Public Library of Science (PLOS ONE) journal published a controversial study in which University of Alberta virologist David Evans and his associate Ryan Noyce synthesized a horsepox virus from bits of mail-ordered genetic material. Noyce and Evans obtained the horsepox DNA, synthesized the genes in a modern vaccinia virus (VACV) to create the horsepox virus (HPXV). Then, they showed that the virus was able to infect cells and reproduce. They describe all their processes in thorough detail in their paper, which was published on Jan. 19, 2018.

This study was funded by Tonix, a pharmaceutical company based in New York, whose president and chief executive officer Seth Lederman is listed as one of the authors on the study.

Horsepox is non-lethal to humans, but it is a relative of smallpox, which was declared to be officially eradicated in 1980 by the World Health Organization (WHO). The WHO also bans the synthesis of the full genome of smallpox. The last strains of variola are kept under high security in Russia and the United States. In 2017, Science magazine reported that motivation for the research, according to its sponsor Seth Lederman, president of the pharmaceutical company Tonix, was to develop a safer, reliable smallpox vaccine with fewer side effects. But critics say that not only do safer vaccines already exist, but also the paper’s publication in an open-source journal could potentially further the threat of a smallpox outbreak via a bioterrorist attack. Gregory Koblentz, a biodefense expert at George Mason University in Arlington, Virginia, explains that while getting hands on the smallpox virus is not an immediate threat, over time as more and more people gain access to this technology, it could become a threat.

The study by Lederman, Evans, and Noyce has been criticized for claiming that it could further the development of a “safe” smallpox vaccine, without mentioning that such vaccines have already been developed and that the market for a smallpox vaccine using horsepox is seemingly nonexistent. In response, Lederman claims that he is not convinced by the clinical trials, or the historical success of other smallpox vaccines like the modified vaccinia Ankara (MVA) or the LC16m8 from Japan.

A weakened form of this vaccinia virus, known as MVA, was developed in the 1970s by the German-Danish company Bavarian Nordic, and was administered to about 150,000 German children at the time. It doesn’t replicate in humans and has been proven to be safe on HIV-positive and stem-cell transplant patients. However, Lederman argues that because MVA was developed and distributed as smallpox was becoming more and more rare, its effectiveness in a real smallpox outbreak remains untested and could be a huge gamble.

Before you panic, you should know that according to the Center for Disease Control and Prevention (CDC), there is a large enough supply of the smallpox vaccine for the American public in case of such an attack. Since 9/11, the U.S. government has stockpiled on millions of doses of vaccinia, the mild poxvirus used in the smallpox vaccine. Today, the U.S. government plans to acquire 13 million more doses of MVA, and already has 28 million, according to Science magazine. This vaccine is less risky than the vaccinia vaccines which were frequently used pre-eradication.

As of now, Tonix is developing vaccines using horsepox that have been tested on microbes, which would have been infected had they not been vaccinated. The company is currently working on a more controlled version of the vaccine that they could test on humans.

The debate around this issue is related to others about whether the remaining strains of the smallpox virus, secured in government labs in the United States and Russia, should be destroyed. In 2014, the WHO had recommended that these labs get rid of the virus--but as CDC scientist Inger Damon stated in Smithsonian that same year, if another outbreak occurred, keeping the strains would be necessary in order to research safer vaccines and treatments. To that end, Lederman, Evans, and Noyce have proven that the reintroduction of smallpox is no longer a theoretical possibility while simultaneously aiding preparedness for such a situation by bringing the topic back into discussion. However, by publishing their paper, many believe that they have also increased the risk of that happening.