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Plague prevention - Immunisation against plague

Immunization studies with candidate plague vaccines in animal models show that neutralizing antibody provides protection against exposure but that cell-mediated immunity is so critical for protection and clearance of Y. pestis from the host.
There is 2 vaccine whole cell vaccine and live attenuated vaccine 
A killed whole-cell vaccine used in humans as many disadvantages
  • Required multiple doses 
  • Caused significant local and systemic reactions
  • It failed to give protection against pneumonic plague
This vaccine is not currently available in the United States.
A live attenuated vaccine 

Live attenuated vaccine based on strain EV76 is still used in countries of the former Soviet Union but has significant side effects. Live attenuated vaccines closest to licensure are subunit vaccines comprising recombinant F1 (rF1) and various recombinant V (rV) proteins produced in Escherichia coli, that are combined either as a fusion protein or as a mixture, purified, and adsorbed to aluminum hydroxide for injection.

This combination will protects mice and various nonhuman primates in laboratory models of bubonic and pneumonic plague and has been evaluated in phase 2 clinical trials. Special ethical considerations with controlled clinical studies involving plague in humans make prelicensure field efficacy studies unlikely.

In the United States, the FDA is hence  prepared to assess plague vaccines for human use under the Animal Rule, using efficacy data and other results from animal studies as well as antibodies and other correlates of immunity from human vaccine recipients

Live attenuated Y. pseudotuberculosis and Salmonella strains expressing Y. pestis–specific antigens found to be  protective in laboratory animal models of bubonic and pneumonic type of plague and it can be also delivered by the oral route.

There is also a wide variety of other delivery mechanisms for Y. pestis antigens are being explored.
Antigens other than F1 and V that can be added to subunit vaccines are being investigated. Advances providing impetus for exploration of these antigens are the following
  • The recovery of F1-negative Y. pestis strains from natural sources 
  • The observation that F1 antigen is not required for virulence in primate models of pneumonic plague