Sarah Bennett
The bubonic plague, caused by Yersinia pestis, is a deadly disease that has historically caused several pandemics and continues to occur annually in rural areas of Africa, Asia, and America. While antibiotics can be used to treat the plague, the emergence of antibiotic-resistant strains and the remote locations of some outbreaks underscore the importance of developing an effective vaccine. Currently, there is no widely available vaccine specifically for the bubonic plague, but several vaccines have shown promise in offering protection against both the bubonic and pneumonic forms of the plague. These include the VTnF1 oral vaccine, which has demonstrated fast-acting immune mechanisms in mice, and the V674pF1 vaccine, a genetically modified Y. pseudotuberculosis candidate. Other vaccines, such as the KWC vaccine and its derivatives, have been used in the past or are still employed in specific regions like China and Russia, but they exhibit limited efficacy against the pneumonic plague and severe side effects. The development of an effective vaccine against the bubonic plague remains an ongoing area of research and is crucial for global health security.
| Characteristics | Values |
|---|---|
| Types of plague | Bubonic, pneumonic, and septicaemic |
| Cause of bubonic plague | Infection through flea bite |
| Bubonic plague fatality rate | 30% to 60% if left untreated |
| Pneumonic plague fatality rate | Almost always fatal |
| Pneumonic plague transmission | Y. pestis can be transmitted to healthy individuals in close contact by respiratory droplets |
| Regions with plague cases | Rural areas of Africa, Asia, and America |
| Regions with plague endemic | China, Mongolia, Burma, Vietnam, Indonesia, India, large parts of Southern Africa, the United States, and South America |
| Vaccine types | Live attenuated, killed, F1 fraction, inactivated bacterial, live whole cell-based, recombinant protein, KWC, USP, and Y. pestis isolate |
| Vaccine side effects | High systemic side effects, severe short-term side effects, adverse effects |
| Vaccine effectiveness | Reduced plague mortality by 50%-85% |
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What You'll Learn
- The first plague vaccine was developed in 1897 by bacteriologist Waldemar Haffkine
- There are three types of vaccines: live attenuated, killed, and F1 fraction
- Killed and attenuated vaccines can protect against bubonic plague but have frequent short-term side effects
- Live whole cell-based vaccines can induce a strong immune response against both bubonic and pneumonic plague but carry a risk of fatal cases
- The lack of high-quality evidence on the effects of plague vaccines makes it difficult to assess their effectiveness and tolerability
The first plague vaccine was developed in 1897 by bacteriologist Waldemar Haffkine
Yes, there are vaccines for the bubonic plague. The first plague vaccine was developed in 1897 by the bacteriologist Waldemar Haffkine. Working in Paris and India at the turn of the 19th century, Haffkine created the world's first vaccines for cholera and the bubonic plague.
Haffkine successfully inoculated rabbits against the plague in December 1896. By January 1897, he was ready to test his vaccine on humans. On 10 January 1897, he injected himself with 10cc of his preparation—a significantly higher dose than the 3cc he planned to use in wider testing. He experienced a severe fever but recovered after several days.
At the end of that month, a plague outbreak occurred at Bombay's Byculla House of Correction, a jail housing hundreds of inmates. Haffkine went there to carry out controlled tests, inoculating 147 prisoners and leaving 172 untreated. There were 12 cases and six deaths among the untreated group, and just two cases and no deaths among those who were inoculated. The apparent success of these tests led to the rapid expansion of production and testing.
Haffkine conducted a massive inoculation program in British India, and it is estimated that 26 million doses of his anti-plague vaccine were sent out from Bombay between 1897 and 1925, reducing plague mortality by 50–85%. In tribute to his achievements, the Bombay Government renamed the laboratory the Haffkine Institute in 1925.
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There are three types of vaccines: live attenuated, killed, and F1 fraction
Yes, there are vaccines for the bubonic plague. The first plague vaccine was developed by bacteriologist Waldemar Haffkine in 1897. Since then, three types of vaccines have been developed: live attenuated, killed, and F1 fraction.
Live attenuated vaccines contain a weakened form of the bacteria or virus that causes the disease. They provoke a strong immune response without causing severe illness. This type of vaccine usually provides lifelong immunity with just one or two doses. However, they may be less effective and are not suitable for everyone, particularly those with weakened immune systems or long-term health problems.
Killed vaccines, on the other hand, use inactivated pathogens, making them safer for vulnerable populations. While they may be more effective and have fewer adverse effects, they do not provide as durable protection as live vaccines.
F1 fraction vaccines appear to have low efficacy (below 60%) and high systemic side effects (35% of vaccinees).
The means of administration for these vaccines vary from oral to nebulised, subcutaneous, and intramuscular.
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Killed and attenuated vaccines can protect against bubonic plague but have frequent short-term side effects
There are three types of vaccines available for the plague: live attenuated, killed, and F1 fraction. The plague is caused by the Yersinia pestis bacterium and has three different forms: bubonic, pneumonic, and septicaemic. The bubonic form, also known as the Black Death, was the biggest global pandemic in history and killed hundreds of millions of people. If left untreated, it has a 30-60% fatality rate.
Killed and attenuated vaccines can protect against the bubonic plague, but they have frequent short-term side effects. The quality of the evidence regarding the vaccines' effectiveness is highly variable and, in some cases, low. However, there is reasonable circumstantial evidence that killed vaccines may be more effective and have fewer adverse effects than attenuated vaccines. Cutaneously administered vaccines tend to have more side effects than their nebulised counterparts but are more effective.
The first plague vaccine was developed by bacteriologist Waldemar Haffkine in 1897. He tested it on himself and then conducted a mass inoculation program in British India, which reduced plague mortality by 50-85%. Since then, various other vaccines have been developed, including a live avirulent EV76 strain vaccine, which has been used for mass immunisation in India, and the Greer vaccine (formerly produced by Cutter Biological Ltd in the USA), a formalin-inactivated vaccine that protects against bubonic plague for several months.
Despite these developments, there is still a lack of high-quality trial evidence regarding the effects of plague vaccines, and long-term side effects remain unknown. More research is needed to evaluate the effectiveness and safety of these vaccines fully.
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Live whole cell-based vaccines can induce a strong immune response against both bubonic and pneumonic plague but carry a risk of fatal cases
Plague vaccines have been in use since 1897, when bacteriologist Waldemar Haffkine developed the first plague vaccine. Haffkine tested the vaccine on himself and later conducted a mass inoculation program in British India. From 1897 to 1925, an estimated 26 million doses of the vaccine were sent out from Bombay, reducing plague mortality by 50-85%.
Today, several types of vaccines are available to prevent plague, including inactivated bacterial vaccines, live attenuated vaccines, and recombinant protein vaccines. Inactivated bacterial vaccines, which use heat-killed cultures of Yersinia pestis organisms, have been used since 1890 but are less effective against pneumonic plague. Live, attenuated vaccines, on the other hand, offer stronger protection against both bubonic and pneumonic plague.
Live whole cell-based vaccines, prepared from fully virulent strains of Y. pestis, have been found to induce a strong immune response against both forms of the plague. However, these vaccines carry a risk of fatal cases due to the ability of live bacilli to colonize and temporarily replicate in the host. Indeed, many fatal cases have been observed in laboratory animal models and non-human primates (NHPs) after vaccination with live vaccines. Nevertheless, no fatal human cases have been reported following the administration of LWC plague vaccines, and millions of people were vaccinated with LWC in the mid-20th century.
Despite the potential effectiveness of LWC-based vaccines, they are associated with several adverse effects, such as fever, malaise, and lymphadenopathy in humans. As a result, safety concerns have limited the enthusiasm for developing live attenuated vaccines in regions where plague is uncommon, such as the United States and Europe.
While the development of vaccines continues to be important in defending populations from the plague, antibiotics remain a viable treatment option for many areas experiencing outbreaks. However, remote locations may benefit more from an effective vaccine as a prevention strategy to combat the disease.
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The lack of high-quality evidence on the effects of plague vaccines makes it difficult to assess their effectiveness and tolerability
Plague vaccines have been in use since 1890, but the evidence for their effectiveness is limited. The plague, caused by the bacterium Yersinia pestis, has three forms: bubonic, pneumonic, and septicaemic, with bubonic and pneumonic plague being able to develop into the life-threatening infection of the blood, septicaemia. The bubonic plague, also known as the Black Death, was the biggest global pandemic in history, killing hundreds of millions of people. Although the plague has been eliminated in much of the world, annual cases still occur in rural areas of Africa, Asia, and America.
The first plague vaccine was developed by bacteriologist Waldemar Haffkine in 1897. Haffkine tested the vaccine on himself and later conducted a mass inoculation program in British India. Between 1897 and 1925, an estimated 26 million doses of Haffkine's vaccine were administered, reducing plague mortality by 50-85%. Despite this historical success, the current understanding of plague vaccines is limited.
A systematic literature review found no evidence for the efficacy of plague vaccines and only limited evidence for their safety and immunogenicity. Only two randomised controlled trials (RCTs) were identified, both in early phases (phase 1 and phase 2a). Neither of these reported efficacy outcomes, and there were differences in their safety and immunogenicity endpoints. While both vaccines were well tolerated with mostly mild to moderate adverse events, the trials only reported short-term data, leaving questions about potential long-term side effects unanswered.
The lack of high-quality evidence on the effects of plague vaccines is a significant issue. It highlights the need for additional, rigorous, long-term studies to properly evaluate the effectiveness and tolerability of these vaccines. Circumstantial data suggests that 'killed' types of vaccines may be more effective and have fewer side effects than 'attenuated' types, but more research is required. The development of a new vaccine is important, especially considering the ongoing occurrence of plague outbreaks and the limitations of current treatments. Antibiotics can be used to treat the plague, but many areas experiencing outbreaks are remote, making an effective vaccine a valuable prevention strategy.
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Frequently asked questions
Yes, there are vaccines that can protect against the bubonic plague. The first plague vaccine was developed by bacteriologist Waldemar Haffkine in 1897.
Currently, there are no licensed vaccines for the bubonic plague. However, there are ongoing vaccine trials at the University of Oxford.
The KWC vaccine, which was manufactured by Cutter Laboratories, was discontinued in 1999 due to severe side effects. The specific side effects are not mentioned.
Live whole cell-based vaccines have also been associated with adverse effects, but there were no fatal human cases reported after administration of the LWC plague vaccine.
The KWC vaccine offered protection against the bubonic plague but was inefficient against the pneumonic plague.
The VTnF1 vaccine candidate provided complete protection against both pneumonic and bubonic plague in mice models.
The VTnF1 vaccine consists of a live, avirulent, genetically modified Yersinia pseudotuberculosis that produces the capsule antigen of Y. pestis, named F1. The F1 antigen plays a key role in avoiding phagocytosis.
