US-2238-93C

Publications

Achievements

Development of a Multivalent Iscom Vaccine against Anaplasmosis	Budget	Duration
	$275,000	3 years

	Palmer, G.H.	WA State U
	Pipano, E.	Isr. Vet. Inst.
	McElwain, T.F.	WA State U
	Shkap, V.	Isr. Vet. Inst.
	Knowles, Jr., D. P.	WA State U

Final Report Abstract
Anaplasmosis is an arthropod+borne disease of cattle caused by the rickettsia Anaplasma marginale and an impediment to efficient production of healthy livestock in both Israel and the United States. Our research focuses on development of a recombinant membrane surface protein (MSP) immunogen to replace current vaccines derived from the blood of infected cattle. The risk of widespread transmission of both known and newly emergent pathogens has prevented licensure of live blood-based vaccines in the U.S. and is a major concern for their continued use in Israel. Briefly, we accomplished the following in our BARD supported research: i) characterization of the intramolecular and intermolecular relationships of the native Major Surface Proteins (MSP) in the outer membrane; ii) expression, purification, and epitope characterization of the recombinant MSP-2, MSP-3, MSP-4, and MSP-5 proteins required to construct the recombinant ISCOM; iii) demonstration that the outer membrane-Quil A induces CD4+ T lymphocytes specific for the outer membrane polypeptides; iv) identification of CD4+ T lymphocytes that recognize outer membrane polypeptide epitopes conserved among other wise antigenically distinct strains; v) determination that immunization with the outer membrane-Quil A construct does not affect the ability of ticks to acquire or transmit A. marginale; and vi) demonstration that the outer membrane-Quil A construct induces complete protection against rickettsemia upon homologous challenge and significant protection against challenge with antigenically distinct strains, including tick transmission. Importantly, the level of protection against homologous challenge in the MSP vaccinates was comparable to that induced by live blood-based vaccines and demonstrates that development of a new generation of vaccines is feasible.