Polio, once among the most dreaded diseases even in the richest countries, has seemed on the verge of eradication for years now—but only on the verge. In a small handful of nations, the virus is holding on stubbornly despite a major vaccination effort backed by the United Nations and philanthropists such as the Bill and Melinda Gates Foundation. Perversely, a current polio outbreak in the Democratic Republic of the Congo is caused by the polio vaccine itself. What explains this seeming paradox? What are the implications for polio eradication? To gain some insight, the Bulletin posed a few questions via e-mail to Christopher K. Brown, a scientist with the Occupational Safety and Health Administration. Brown holds degrees in biodefense, biostatistics and epidemiology, and biology—and just weeks ago wrote about Ebola vaccine for the Bulletin. A lightly edited version of his answers to the Bulletin’s questions appears below.
Bulletin of the Atomic Scientists: A current polio outbreak in the Democratic Republic of the Congo is caused not by a “wild” poliovirus but rather by a virus derived from oral polio vaccine. How does a vaccine end up causing the very illness it’s intended to prevent?
Christopher K. Brown: There are several different ways to make a vaccine, one of which involves weakening the pathogen that causes the disease so that, ideally, it triggers the vaccine recipient’s immune system to recognize and fight off the pathogen without actually causing a case of disease. Because weakened—or attenuated, as they are called—vaccines still include a live, virulent organism, they are in very rare instances linked to disease, whether in a single individual or as the culprit behind an outbreak. Scientists do not fully understand why the intentional infection that the oral poliovirus vaccine causes might lead to unintended disease in an extremely small number of vaccinated people, but it is likely that having a weakened immune system may contribute to someone experiencing paralysis after getting the attenuated vaccine.
The process by which an attenuated vaccine leads to a larger outbreak is more complicated. When someone gets the vaccine, the viruses it contains replicate in the small intestine. The weakened viruses can then spread from person to person. This can be a good thing in that it offers immunity to people who are exposed through this type of transmission even though they didn’t get the vaccine themselves—and thus it increases the proportion of the population that most likely will not get polio even if exposed to poliovirus (that is, it bolsters herd immunity). But if a vaccine-derived strain of the virus continues to spread and replicate, mutations in its RNA (the genetic material that controls the virus) can over time allow it to revert to a form capable of causing disease, including paralysis, as we are seeing among children in the Democratic Republic of the Congo. If most of a population is not immune to the particular strain, then more people may start to develop disease as a result of the vaccine strain becoming virulent again.
Bulletin: Do vaccines for other diseases—influenza, for example—sometimes cause the diseases they’re supposed to stop?
Brown: Attenuated vaccines work by introducing a form of a certain bacterium or virus into a person’s body so that the body learns to recognize and fight that pathogen. Essentially, it causes an “infection light” that is designed to produce no, or only very mild, symptoms while still triggering the immune response necessary to give the recipient future protection against the pathogen. That’s why, in very rare cases, someone might develop a chicken pox–like rash after getting the chicken pox vaccine, for example. Other vaccines, like measles-mumps-rubella, yellow fever, and some types of nasal flu mist, are also made from live, attenuated pathogens that are modified to produce an immune response without causing symptomatic infection. Rarely, they can still result in some side effects without actually causing a full-blown case of the disease they’re supposed to prevent. Importantly, those side effects are almost, if not always, much less severe than the disease itself would be in an unvaccinated person.
Bulletin: A recent article in Science reports that “circulating vaccine-derived polioviruses have emerged as the greatest threat to polio eradication.” Surely it can’t be logical to conclude from that statement that the best way to reduce polio cases is to cease distribution of polio vaccine. But why exactly is it illogical?
Brown: It’s all about timing and vaccination strategy. Vaccinating people with an attenuated strain of poliovirus that is thought to have been nearly eradicated means a continued risk that the vaccine strain will mutate back into a form capable of causing disease, namely vaccine-associated paralytic poliomyelitis. But when that does happen, and we see a vaccine-derived poliovirus outbreak, the at-risk population needs to be immunized to stop the outbreak.
In the Democratic Republic of the Congo, a vaccine-derived type 2 poliovirus is responsible for the current outbreak, even though it is no longer a component of the live, attenuated oral vaccine that most countries use (when, that is, an oral, attenuated vaccine is used instead of a fully inactivated injectable formulation that is safer but potentially less effective). Despite a World Health Organization–led switch from the three-type, or trivalent, vaccine to a bivalent preparation, the vaccine-derived type 2 virus continued to spread from person to person undetected, slowly mutating to regain the neurovirulence that can cause paralysis in those who are infected.
Now, to stop the current outbreak, health officials are deploying a monovalent vaccine formulated specifically for type 2 poliovirus. The key is to reach susceptible individuals—namely, those who did not receive the trivalent option previously—with the vaccine before the virulent strain of the virus does. If enough people are vaccinated, the mutated, vaccine-associated strain will not continue to infect new people and the outbreak will subside.
Bulletin: Are you concerned that the anti-vaccination crowd will seize on this vaccine-derived polio outbreak to argue against vaccination more broadly?
Brown: It’s certainly possible that someone could argue against vaccination by pointing to an outbreak of disease caused by a vaccine-derived strain of poliovirus, especially an outbreak in which children have been paralyzed. However, the argument that vaccines cause injury often focuses on the myth that certain chemicals in vaccines—including preservatives, like Thiomersal, that are no longer used in vaccine formulations—cause autism. The polio outbreak in the Democratic Republic of the Congo is a case in which a strain of virus that was rendered safe for vaccinating most people has regained some of its disease-causing abilities through genetic mutation. That’s sort of similar to why bugs that are more common problems in developed countries, like staphylococcus and gonorrhea, stop responding to antibiotics: They acquire genetic mutations that make them resistant to certain drugs. What is most important here is to consider the level of risk associated with vaccine-linked outbreaks, or cases of paralysis, compared to the effects of polio in an unvaccinated population. While the attenuated poliovirus in the vaccine itself may lead to no more than four or five cases of paralysis among every million individuals vaccinated, there would likely be thousands of cases of serious disease among a million exposed, unvaccinated people.
Bulletin: When Canadian researchers used the gene-editing tool Crispr to synthesize horsepox in 2016—incidentally demonstrating that it was also possible to reconstitute smallpox—many observers were alarmed. Once polio is eradicated, could the virus be reconstituted with Crispr? Would reconstituted polio in the hands of malicious actors represent a significant security threat?
Brown: Actually, before those researchers recreated the horsepox virus in 2016, a team of virologists had already built an infectious poliovirus very similar to the wild-type virus. Crispr may make this process easier and less expensive, but polio, while a significant public health problem, does not make a very good weapon for a bioterrorist. Polio generally spreads through fecal-oral transmission, meaning the virus needs to be ingested so that it can make its way to its preferred site of infection in the small intestine. Even if a wide-area release of the virus were used to contaminate food or water supplies, poliovirus would be fairly unstable in an aerosol used to disseminate it and could be inactivated with chlorine-based sanitizers. In countries where childhood uptake of a fully inactivated poliovirus vaccine is high, the population is not likely to be susceptible to strains of the poliovirus that the vaccine protects against. A malicious actor would need to recreate not just an eradicated virus, but one capable of evading the vaccine-conferred immunity within the population—arguably a more challenging task.
This interview was conducted in Brown’s personal capacity. The opinions expressed here are his own and do not necessarily reflect those of his employer or any other US government agency.
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