Plague vaccine: recent progress and prospects

Abstract

Three great plague pandemics, resulting in nearly 200 million deaths in human history and usage as a biowarfare agent, have made Yersinia pestis as one of the most virulent human pathogens. In late 2017, a large plague outbreak raged in Madagascar attracted extensive attention and caused regional panics. The evolution of local outbreaks into a pandemic is a concern of the Centers for Disease Control and Prevention (CDC) in plague endemic regions. Until now, no licensed plague vaccine is available. Prophylactic vaccination counteracting this disease is certainly a primary choice for its long-term prevention. In this review, we summarize the latest advances in research and development of plague vaccines.

Two fatal cases of plague after consumption of raw marmot organs

“…Y. pestis infection occurred even though the man had received an EV76 vaccine one year previously. There is no evidence showing that the available Y. pestis vaccines provide humans with long-lasting immunity and protection from plague [8,9].…”

Immunogenicity of trimeric autotransporter adhesins and their potential as vaccine targets

“…Currently, there are no licensed vaccines targeting Y. pestis and Y. pseudotuberculosis [71]. Earlier human vaccines comprising live-attenuated Yersinia strains or killed whole-cell bacteria [72] often caused severe side reactions or proved to be too reactogenic, respectively [72][73][74][75].…”

“…Earlier human vaccines comprising live-attenuated Yersinia strains or killed whole-cell bacteria [72] often caused severe side reactions or proved to be too reactogenic, respectively [72][73][74][75]. Some vaccines are in clinical trials (e.g., rF1-V and RYpVax) and seem the ideal approach to overcome more outbreaks of Y. pestis by providing pre-exposure prophylaxis to combat infection for individuals with a high risk of exposure [71]. Important to note is, however, the fact that Y. pestis does not express YadA precluding its use as a potential plague vaccine candidate.…”

“…Palmer et al demonstrated the ability of Y. enterocolitica to modulate the immune response via OMPs [77]. More recently, the effective use of a bivalent fusion protein consisting of immunologically active regions of Y. pestis LcrV (i.e., a 35 kDa secreted protein that mediates the transport effector proteins into the host cell [71,75]) and YopE proteins gave mice immunogenic protection upon delivery of lethal Y. enterocolitica [78]. New screening approaches for the development of vaccine candidates are still necessary, for instance, in vivo signature-tagged mutagenesis to target genes for novel virulence factors [79] or the use of reverse vaccinology to screen for antigenic OMPs.…”

Development of a double‐antibody sandwich ELISA for sensitive detection of Yersinia pestis

“…The F1 protein is expressed at mammalian body temperature and can be secreted in the host during the infection . The F1 protein, along with the V protein, is being developed as a major candidate for a plague vaccine . As the F1 protein is found only in Y. pestis , it has been used as a specific marker for identification of the bacteria …”