The plague is an infectious disease caused by the bacterium Yersinia pestis, a microbe found in small mammals and their fleas. While this illness is widely recognized for its devastating historical pandemics, such as the Black Death, it continues to exist in various parts of the world today. Between one thousand and two thousand cases are reported annually to the World Health Organization. Throughout history, efforts have been made to develop vaccines to protect against this serious disease.
Historical Development of Plague Vaccination
The development of the first effective plague vaccine was a major achievement in bacteriology. Russian-French bacteriologist Waldemar Haffkine pioneered this effort, creating his vaccine in 1897. This early vaccine consisted of a heat-killed culture of Yersinia pestis, inactivated by heating to 60°C.
Haffkine personally tested the vaccine on himself to demonstrate its safety before it was widely deployed. Following this, a large-scale inoculation program was initiated in British India during the Third Pandemic. An estimated 26 million doses of Haffkine’s anti-plague vaccine were distributed from Bombay between 1897 and 1925, which helped reduce plague mortality by approximately 50% to 85%. This breakthrough marked one of the earliest successful bacterial vaccines.
Current Plague Vaccine Availability
A formal plague vaccine is no longer commercially available in the United States. The inactivated whole-cell vaccine, known as Plague Vaccine, USP, was discontinued by its manufacturer in 1999. Its use was highly restricted even when it was available, and it was never recommended for the general public.
Vaccination was primarily reserved for specific at-risk populations. These groups included laboratory personnel who routinely worked with Yersinia pestis or were involved in aerosol experiments with the bacterium. Military personnel deployed to regions where plague was endemic or where exposure was unavoidable were also recommended for vaccination. The vaccine was not advised for most travelers or individuals living in areas with enzootic plague due to other effective preventive measures.
Efficacy and Protective Limitations
The killed whole-cell plague vaccine had several limitations that hindered its widespread use. It provided only partial and often short-term protection, primarily against the bubonic form of the disease. The vaccine was not reliably effective in preventing the more dangerous pneumonic plague, which can spread rapidly between people.
Recipients of the vaccine frequently experienced common side effects. These reactions included pain, swelling, and redness at the injection site, along with systemic symptoms such as fever, headache, and general malaise. These reactions tended to occur more frequently with repeated booster injections needed to maintain protection. The combination of the vaccine’s limited efficacy, particularly against pneumonic plague, and its reactogenicity, lessened its appeal for broad public health use. The availability of effective antibiotic treatments for plague also diminished the perceived need for widespread vaccination.
Modern Research and Vaccine Candidates
Ongoing scientific efforts are focused on developing improved plague vaccines that address the shortcomings of older formulations. One promising approach involves subunit vaccines, which utilize specific components of the bacterium rather than the entire killed organism. Researchers are particularly interested in the F1 capsular antigen and the V antigen, a virulence protein, as targets for these new vaccines. These subunit vaccines aim to induce a strong immune response with potentially fewer side effects.
Experimental fusion proteins, such as recombinant F1-V, have shown encouraging results in animal models. These candidates have demonstrated the ability to elicit antibody responses and provide protection against both bubonic and pneumonic forms of plague. Other avenues of research include developing live-attenuated vaccines, which use weakened living bacteria to stimulate immunity, and exploring newer technologies. For example, messenger RNA (mRNA) vaccine platforms, similar to those used for COVID-19, are being investigated. Early studies in animal models with mRNA-based plague vaccines have shown complete protection against lethal pneumonic plague after a single dose.