Babesia microti cysteine protease-1 as a target for vaccine development

Babesia species have a worldwide distribution, affecting a wide range of mammalian hosts. The major route of transmission is inoculation by an infected Ixodid tick. Babesia species of major economic concern are those that cause bovine and equine babesiosis. Historically, bovine Babesia species, Babesia bovis and Babesia bigemina caused significant economic losses in the United States in the 1860??????s, as thousands of cattle died. Also, outbreaks of equine babesiosis, caused by Babesia equi or Babesia caballi, have occurred in the United States resulting in the death of some horses and millions of dollars in losses. A constant risk of reinfection with bovine and equine Babesia species exists, as stray and smuggled animals from Mexico, where bovine babesiosis is endemic, may carry infected ticks as they cross the border, and, thousands of horses from B. equiand B. caballi-endemic regions are imported through Florida every year. Vaccines have been developed for a number of Babesia species, none of which result in sterile immunity. The live attenuated vaccine is the most commonly used vaccine against Babesia species. However, the basis for the vaccine is to maintain a carrier state in order to prevent disease. Other vaccine designs have been developed to invoke protection without a carrier state but have been unsuccessful. It has been shown that the cysteine protease is important in the life cycle of a number of parasitic organisms, making it a good target for vaccine development. The vaccine design for this study incorporated the cysteine protease of Babesia microti. Babesia microti naturally infects Peromyscus leucopus (white-footed mouse) and is the major cause of human babesiosis in the United States. Using B. microti in the vaccine design allowed for the use of a mouse model to determine whether the cysteine protease of other economically important Babesia species may make a good vaccine target. The vaccine design incorporated a prime-boost strategy, priming with DNA encoding the cysteine protease and boosting two times with either DNA encoding the cysteine protease or cysteine protease peptide, followed by parasite challenge. Analysis of daily percent parasitemias, packed cell volume, and seroconversion of all groups revealed that a protective immune response against B. microti was not elicited by this vaccine strategy.