While vaccines against the bubonic plague have been developed for over a century, none are currently licensed for the general public in the United States or Europe. The plague, caused by the bacterium Yersinia pestis, spurred early efforts to create preventative vaccines that saw use for decades. However, their limitations led to their discontinuation for widespread use, and today vaccination is reserved for a small number of high-risk people while research focuses on safer alternatives.
Historical Vaccine Development
The first major breakthrough in plague prevention occurred in 1897, when bacteriologist Waldemar Haffkine developed the first effective vaccine in India. Haffkine created a killed whole-cell (KWC) vaccine by inactivating Yersinia pestis bacteria with heat. He famously tested the initial formulation on himself to demonstrate its safety before it was deployed on a larger scale.
Haffkine’s vaccine was used extensively in British India, with millions of doses administered in the following decades, and it was credited with significantly reducing mortality rates among those who received it.
The KWC vaccine was still used for specific applications into the 20th century. For instance, the United States military administered it to service members during the Vietnam War. This was done to protect personnel operating in regions where plague was present in local wildlife populations.
Discontinuation of Widespread Use
A primary issue with the KWC vaccine was its limited effectiveness. While it offered some protection against the bubonic form of plague, its efficacy against the more aggressive pneumonic form was questionable. Cases of pneumonic plague, which spreads through respiratory droplets, were reported in vaccinated individuals.
The vaccine also caused a high rate of adverse reactions. Recipients frequently experienced malaise, headache, fever, and painful swelling at the injection site. These common side effects made the vaccine unpopular and difficult to administer in mass campaigns.
The discovery of antibiotics like streptomycin and doxycycline fundamentally changed the approach to managing plague. These drugs are highly effective at treating the infection, especially when administered early. The ability to cure plague with antibiotics meant a preventative vaccine with partial efficacy and notable side effects was no longer the primary public health tool.
Current Vaccine Status and Modern Research
With the KWC vaccine no longer in production, scientific inquiry is aimed at creating a modern vaccine. The goal is to develop a vaccine that is safe, well-tolerated, and provides long-lasting immunity against all forms of the disease.
Current research is concentrated on subunit vaccines, which use specific components of Yersinia pestis to trigger an immune response. Scientists have identified two proteins, the F1 antigen and the V antigen (LcrV), as promising candidates. Combining these antigens may provide protection without the side effects associated with whole-cell preparations.
Scientists are also exploring mRNA and DNA vaccine platforms for plague, which gained prominence during the COVID-19 pandemic. These platforms use genetic instructions to teach the body’s cells how to produce a bacterial antigen. Early studies in animal models show that mRNA vaccines can elicit strong immune responses, suggesting this could be a rapid way to develop a protective vaccine.
Who Needs a Plague Vaccine Today?
Because plague is rare and treatable with antibiotics, vaccination is not recommended for the general public. Even people living in regions where plague is found in wild animals, such as the western United States, do not require it. Preventative recommendations focus on avoiding contact with wild rodents and treating pets for fleas.
The World Health Organization and the U.S. Centers for Disease Control and Prevention (CDC) identify a narrow set of high-risk groups for whom a future vaccine would be considered. The primary candidates are laboratory personnel who work directly with live Yersinia pestis cultures, as their work involves direct exposure.
Another group includes professionals like veterinarians and wildlife biologists who have regular contact with wild rodents and their fleas in areas where plague is endemic. Military personnel deployed to regions with active plague outbreaks or as a biodefense measure could also be considered for vaccination.