Live Experimental Pneumonic Plague Vaccines Being Developed After Repeated Attempts

University of Texas Medical Branch (UTMB) researchers have developed live attenuated experimental pneumonic plague vaccines that, according to a July 28, 2026 press release, fully protected mice in a preclinical study. The findings were published in Science Translational Medicine and, according to UTMB researchers, “challenge decades of assumptions about how immunity to plague works and could help guide the development of more effective vaccines against the highly lethal disease.”¹

“Plague” refers to an infectious disease caused by the bacterium Yersinia pestis that can take several forms, most commonly bubonic, septicemic, or pneumonic plague. Pneumonic plague occurs when Y. pestis bacteria infect the lungs, either after the bacteria spread to the lungs from another form of plague or through inhalation of infectious respiratory droplets from a person or animal with pneumonic plague. According to the U.S. Centers for Disease Control and Prevention (CDC), symptoms include fever, headache, weakness, and rapidly developing pneumonia accompanied by shortness of breath, chest pain, cough, and sometimes bloody or watery mucus.² Reportedly, the death rate for people left untreated for pneumonic plague is close to 100 percent but for people who are treated, it is between 10 and 50 percent.³

According to Jian Sha, PhD, an assistant professor in the Department of Microbiology and Immunology at UTMB, the research focused on two live attenuated plague vaccines. “The research evaluated two live attenuated plague vaccines developed at UTMB, both individually and in combination with a virus-based vaccine carrying three plague antigens. The live bacterial vaccines were tested in both normal mice and mice genetically engineered to lack interferon-gamma (IFN-γ), a signaling protein that helps coordinate immune responses to many bacterial infections.” The animals were then exposed to Y. pestis post-vaccination and nearly all the mice survived.⁴

Neither the UTMB press release nor the published study reported whether the live-attenuated Y. pestis vaccine strain bacteria used in the two candidates can be shed and infect close contacts following vaccination, which is the case for live attenuated viral vaccines such as live oral polio (OPV), live nasal influenza, and live chickenpox vaccines.⁵ Most bacterial vaccines that have been developed in the past contain inactivated (killed) bacteria to minimize the ability of lab-altered live pathogenic bacteria to harm the person being vaccinated (especially if the person is immune compromised) or for the shedding bacteria to be released into the environment.⁶

Plague Vaccine Development Dates Back More Than a Century

The UTMB experimental plague vaccine candidates follow more than a century of research, development and use of earlier plague vaccines. The U.S. Plague Vaccine USP, a killed, formaldehyde-inactivated bacterial vaccine manufactured first by Cutter Laboratories and later by Greer Laboratories, was discontinued in 1999. According to a 2024 npj Vaccines review, production was discontinued largely because of “severe side effects” and its limited effectiveness against pneumonic plague.⁷

Live-attenuated plague vaccines have also been developed and administered to millions of people worldwide. However, concerns about adverse reactions, residual virulence and the possibility that attenuated strains could revert to a disease-causing form have limited their widespread use and prevented licensure in the U.S. and other Western countries.⁸

Despite No Controlled Clinical Trials More Than One Million U.S. Military Personnel Received Plague Vaccine

According to a 2016 review published in Advances in Experimental Medicine and Biology, the U.S. Plague Vaccine USP was administered to more than one million U.S. servicemembers during the Vietnam War, despite no reported controlled clinical trials establishing its effectiveness. Although observational studies among military personnel suggested that it provided some protection against bubonic plague, effectiveness against the pneumonic plague was never established. Experimental studies found the vaccine generally failed to protect mice and nonhuman primates against pulmonary exposure to Y. pestis, and cases of pneumonic plague still occurred among vaccinated people.⁹

The review states:

Controlled clinical trials have not been reported, but studies of United States military personnel during the Vietnam War strongly suggest that formalin-killed, whole-cell vaccines protect against bubonic plague. However, these vaccines cause significant adverse reactions, particularly after booster injections, which are needed to maintain protection. Moreover, they generally fail to protect mice and non-human primates against pulmonary Y. pestis challenge, and several humans contracted pneumonic plague despite immunization with this vaccine. In the US since 1999, lack of effective protection against pneumonic plague, adverse reactions such as fever, headache, lymphadenopathy and the need for booster injections eventually resulted in diminished interest of the USP vaccine.¹⁰

Bioterrorism Concerns Drive Continued Plague Vaccine Development

Despite the extremely low incidence of cases of bubonic or pneumonic plague in the U.S., development of a plague vaccine has remained an area of scientific interest, in part because of concerns about the use of Y. pestis as a biological weapon. The same 2016 review says “plague remains as one of the top five bioterrorism threats and a CDC Tier 1 Select Agent pathogen. Therefore, there is an urgent need for effective means of pre-exposure and post-exposure prophylaxis.”¹¹ The Federal Select Agent Program currently continues to classify Y. pestis as a Tier 1 select agent.¹²

In 2011, the U.S. National Institutes of Health (NIH) awarded UTMB professor Ashok Chopra, PhD, $1.7 million over the following five years to “support his efforts to find new ways to fight plague.”¹³ Chopra, the study’s senior investigator and the John S. Dunn Distinguished Chair in Global Health in the Department of Microbiology and Immunology, commented on the preclinical study findings of the experimental plague vaccine, saying they “generate a remarkably broad immune response.”

Animal Protection Does Not Establish Vaccine Safety and Effectiveness in Humans

Plague is rare in the U.S., treatable with antibiotics when caught promptly, and routine vaccination isn’t currently recommended. According to the CDC, the U.S. sees an average of seven human plague cases a year.¹⁴

UTMB researchers emphasized that the findings are based on animal studies and additional research is needed before the vaccines can be tested in humans. No plague vaccine is currently approved by the U.S. Food and Drug Administration (FDA).¹⁵

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