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Title: Identification of a cell epitope that is globally conserved among outer membrane proteins (OMPs) OMP7, OMP8, and OMP9 of anaplasma marginale strains and with OMP7 from the A. marginale subsp. centrale vaccine strain

Author
item DERINGER, JAMES - Washington State University
item FORERO-BECERRA, ELKIN - Federal University - Brazil
item Ueti, Massaro
item TURSE, JOSHUA - Cornell University
item FUTSE, JAMES - University Of Ghana
item Noh, Susan
item PALMER, GUY - Washington State University
item BROWN, WENDY - Washington State University

Submitted to: Clinical and Vaccine Immunology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 10/13/2016
Publication Date: 10/26/2016
Citation: Deringer, J.R., Forero-Becerra, E.G., Ueti, M.W., Turse, J.E., Futse, J.E., Noh, S.M., Palmer, G.H., Brown, W.C. 2016. Identification of a cell epitope that is globally conserved among outer membrane proteins (OMPs) OMP7, OMP8, and OMP9 of anaplasma marginale strains and with OMP7 from the A. marginale subsp. centrale vaccine strain. Clinical and Vaccine Immunology. doi: 10.1128/CVI.00406-16.

Interpretive Summary: Anaplasma marginale, the causative agent of bovine anaplasmosis, infects red blood cells and causes anemia, weakness and in some cases, death in cattle and wild ruminant species. This tick transmitted bacterial pathogen is responsible for significant economic losses to beef and dairy cattle industries worldwide. Current control methods are inadequate and rely on heavy use of acaricides to prevent tick feeding or use of antibiotics to treat affected animals. Acaricides are expensive, can present an environmental hazard and heavy use leads to resistance within tick population. Antibiotic use is problematic in extensive rearing conditions and there is increasing pressure to decrease the use of antibiotics in domestic animals to help prevent antibiotic resistance. The long term goal of this research is to develop a vaccine to prevent anaplasmosis. Toward that end, in this study, we identify highly conserved regions of outer membrane proteins that can serve as vaccine targets. Importantly, these regions are recognized by the immune system of protectively immunized animals. These regions are identical when comparing strains of A. marginale from geographically diverse regions, including Australia, Brazil and West Africa. This conservation is important because ideally a single vaccine will be able to provide protection against most, if all strains of A. marginale.

Technical Abstract: Within the protective outer membrane fraction of Anaplasma marginale, several vaccine candidates have emerged, including a family of outer membrane proteins (OMPs) 7-9, which share sequence identity with each other and with the single protein OMP7 in the vaccine strain A. marginale subsp. centrale. A. marginale OMPs 7-9 are logical vaccine candidates because they are surface exposed, present in the protective outer membrane (OM) immunogen and cross-linked OM proteins, recognized by immune serum IgG2 and T-cells in cattle immunized with the protective OM immunogen, and recognized by immune serum IgG2 from cattle immunized with the A. centrale vaccine strain. We report the identification of a globally conserved 9-amino acid CD4 T-cell epitope FLLVDDAI/VV shared between A. centrale vaccine strain OMP7 and the related A. marginale OMPs 7-9, where P8 can be isoleucine or valine. The epitope is conserved in American A. marginale strains, in the Australia Gypsy Plains strain, and in multiple field isolates from Ghana. This epitope, together with additional T-cell epitopes that are present within these proteins, should be considered for inclusion in a multivalent vaccine for A. marginale that can provide protection against disease caused by geographically distant bacterial strains.