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

Babesia species have a worldwide distribution, affecting a wide range of mammalian\nhosts. The major route of transmission is inoculation by an infected Ixodid tick. Babesia\nspecies of major economic concern are those that cause bovine and equine babesiosis.\nHistorically, bovine Babesia species, Babesia bovis and Babesia bigemina caused\nsignificant economic losses in the United States in the 1860’s, as thousands of cattle\ndied. Also, outbreaks of equine babesiosis, caused by Babesia equi or Babesia caballi,\nhave occurred in the United States resulting in the death of some horses and millions of\ndollars in losses. A constant risk of reinfection with bovine and equine Babesia species\nexists, as stray and smuggled animals from Mexico, where bovine babesiosis is endemic,\nmay carry infected ticks as they cross the border, and, thousands of horses from B. equiand\nB. caballi-endemic regions are imported through Florida every year.\nVaccines have been developed for a number of Babesia species, none of which result\nin sterile immunity. The live attenuated vaccine is the most commonly used vaccine\nagainst 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\nprotection without a carrier state but have been unsuccessful.\nIt has been shown that the cysteine protease is important in the life cycle of a number\nof parasitic organisms, making it a good target for vaccine development. The vaccine\ndesign for this study incorporated the cysteine protease of Babesia microti. Babesia\nmicroti naturally infects Peromyscus leucopus (white-footed mouse) and is the major\ncause of human babesiosis in the United States. Using B. microti in the vaccine design\nallowed for the use of a mouse model to determine whether the cysteine protease of\nother economically important Babesia species may make a good vaccine target. The\nvaccine design incorporated a prime-boost strategy, priming with DNA encoding the\ncysteine protease and boosting two times with either DNA encoding the cysteine\nprotease or cysteine protease peptide, followed by parasite challenge. Analysis of daily\npercent parasitemias, packed cell volume, and seroconversion of all groups revealed that\na protective immune response against B. microti was not elicited by this vaccine strategy.