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 1860Ã¢Â?Â?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.
Advisor:Holman, Patricia; Jensen, James; Tizard, Ian
School:Texas A&M University
School Location:USA - Texas
Source Type:Master's Thesis
Date of Publication:08/01/2005