Part 1 The Plague concerns an outbreak of bubonic plague in the French-Algerian port city of Oran, sometime in the s. The first-person narrator is unnamed but mostly follows Dr.
To view a copy of this license, visit http: Abstract Despite many decades of intensive studies of Yersinia pestis, the causative agent of plague, there is no safe and efficient vaccine against this devastating disease.
In addition, those developing next-generation plague vaccines need to pay particular attention to the importance of eliciting cell-mediated immunity. In this review, we analyzed the current progress in developing subunit, DNA and live carrier platforms of delivery by bacterial and viral vectors, as well as approaches for controlled attenuation of virulent strains of Y.
Plague, protective antigens, vaccine, Yersinia pestis Introduction Plague is a devastating infectious disease caused by Yersinia pestis that by estimate has claimed about millions of human lives throughout history.
The latter type of transmission can result in a highly lethal pneumonic form of plague. The possibility of aerosolization of the agent, including human-to-human spread, is of particular concern in the case of naturally occurring epidemics or acts of bioterrorism and use of Y.
In this respect, creation of an efficient and safe plague vaccine could be considered an immediate priority. Brief history of plague vaccines killed whole-cell KWC and live whole-cell LWC The search for vaccines to prevent plague began in when French scientist Alexandre Yersin tested plague immunity in laboratory animals rabbits, mice, rats after repeated immunization with either whole-cell, heat-killed, and agar-grown cultures of Y.
The KWC preparations contained microbial cells inactivated by controlled procedures, such as heating or addition of different disinfectants.
These vaccines contained no live pathogen, were unconditionally safe, and produced immunity in animal models to bubonic, but not pneumonic, plague after a single injection. Live attenuated variants of Y.
These vaccines were found to elicit the prompt over several days development of plague immunity against both bubonic and pneumonic forms of plague that correlated with the ability of bacteria to colonize and temporarily proliferate in tissues and organs of the mammalian host.
Therefore, the use of the LWC plague vaccine was generally associated with a risk of the development of an uncontrolled infectious process due to the existence of residual virulence. Hence, fatal cases of plague have been seen in small-animal models and non-human primates following administration of live vaccines.
Both vaccines require annual boosting, prompting the development of less reactogenic, and more safe and efficient vaccines for plague. Importantly, these vaccines eliminated risk factors associated with the use of live vaccine and significantly reduced undesirable side effects linked to the massive administration of a mixture of numerous antigens existing in whole-cell killed vaccines.
Nevertheless, intensive clinical trials are necessary to prove that these vaccines are safer and can provide better immunity than KWC and especially LWC vaccine.
Recombinant subunit vaccines in small animal models Two antigens, namely, capsular subunit protein F1 and the low-calcium response V antigen LcrV were proven to be best in eliciting protection against plague in different animal models.
The recombinant F1 demonstrated similar levels of protection against either subcutaneous or aerosol challenge of mice with the wild-type Y. To immunize animals, alhydrogel was most often the adjuvant of choice, although poly-L-lactide microspheres, MPL, CpG, TiterMax, flagellin, and so forth, were tested as well.
A table listing vaccine formulation, type of adjuvant, animal model, route of immunization and challenge with Y. Usually the addition of F1 improved protection, although, in some studies, the contribution of F1 was negligible; iii in many cases, the level of protection correlated with the titers of antigen-specific IgG1.
Non-encapsulated strains of Y. The latter was efficient mainly in protection against capsule-negative variants of Y. To achieve notable protection, DNA vaccination required boosting with a homologous protein antigen.
The inclusion in the constructs of the molecular immunopotentiator interleukin, or the use of mucosal adjuvant CT cholera toxindid not significantly improve the immunity. This well-developed system for DNA vaccination with LcrV allowed elicitation of a significant antibody response and provided protection against intranasal challenge with Y.
Similar constructs expressing F1 demonstrated much lower protection. Bacterial, viral and plant platforms Development of plague vaccines based on the expression of protective antigens of Y. There are obvious limitations to this type of vaccines, since they require a precise level of attenuation, especially when expressing protective antigens, which often are factors of virulence.The Plague concerns an outbreak of bubonic plague in the French-Algerian port city of Oran, sometime in the s.
The first-person narrator is unnamed but mostly follows Dr. Bernard Rieux. Rieux notices the sudden appearance of dying rats around town, and soon thousands of rats are coming out into.
A history of the bacterial disease of bubonic plague, and of the mortality, distress and panic fear that it caused in the British Isles from The Great Pestilence of to The Plague of London in , with a brief account of its transient reappearances between and /5(1).
Plague (Black Death) is a term applied to an infectious disease that spreads easily and, without antibiotics treatment, can be fatal.
Learn about plague disease symptoms, causes, history, and types: bubonic, septicemic, and pneumonic. Nov 07, · Introduction. Plague is a devastating infectious disease caused by Yersinia pestis that by estimate has claimed about millions of human lives throughout history.
1 It is a zoonotic disease that remains endemic in many parts of the world, exists in the form of natural reservoirs and causes periodic outbreaks in susceptible rodents.
2 Humans are accidental hosts, because they can contract. Introduction. The bubonic plague has been considered one of the most devastating events to hit Europe in history.
The first epidemic of the plague occurred in the Roman Empire around A.D. The. The Black Death created a race for survival and all were playing. As they continued to run from the plague, the people of Europe felt that they needed to blame someone for causing the outrage.
At this time in history, Christians persecuted Jews in Europe and blamed them for bad luck and even bad weather.