Date Published: July 10, 2019
Publisher: Public Library of Science
Author(s): James E. Futse, Grace Buami, Boniface B. Kayang, Roberta Koku, Guy H. Palmer, Telmo Graça, Susan M. Noh, Roman R. Ganta.
A primary challenge in developing effective vaccines against obligate, intracellular, bacterial tick-borne pathogens that establish persistent infection is the identification of antigens that cross protect against multiple strains. In the case of Anaplasma marginale, the most prevalent tick-borne pathogen of cattle found worldwide, OmpA is an adhesin and thus a promising vaccine candidate. We sequenced ompA from cattle throughout Ghana naturally infected with A. marginale in order to determine the degree of variation in this gene in an area of suspected high genetic diversity. We compared the Ghanaian sequences with those available from N. America, Mexico, Australia and Puerto Rico. When considering only amino acid changes, three unique Ghanaian OmpA variants were identified. In comparison, strains from all other geographic regions, except one, shared a single OmpA variant, Variant 1, which differed from the Ghanaian variants. Next, using recombinant OmpA based on Variant 1, we determined that amino acid differences in OmpA in Ghanaian cattle as compared to OmpA Variant 1 did not alter the binding capacity of antibody directed against OmpA Variant 1, supporting the value of OmpA as a highly conserved vaccine candidate.
The identification of protective antigens is a primary limitation of vaccine development against obligate, intracellular pathogens that use antigenic variation to establish persist infection within the mammalian host. These pathogens include, though are not limited to bacteria in the family Anaplasmataceae, such as Anaplasma marginale, A. phagocytophilum and Ehrlichia ruminantium. A. marginale causes bovine anaplasmosis which is a production limiting disease of cattle that occurs worldwide . A single vaccine that protects against antigenically distinct variants is a high priority. This is particularly true for farmers in tropical regions of the world in which high infection prevalence and transmission pressure leads to pathogen diversification .
One of the major limitations of developing a vaccine against A. marginale is strain diversity and the inability to produce cross-protection against a variety of field strains with a single vaccine. Consequently, vaccine development and antigen selection have focused on the identification of outer membrane proteins that are broadly conserved across distant geographic areas. For example, Omp 5, 9, 12, 13 and 14 are invariant during acute and persistent infection as well as tick transmission . However, all of these Omps have variation between strains even when comparing strains from N. America including St. Maries, Florida, S. Idaho, Washington-Okanogan, and Oklahoma . Specifically, for Omp5, the maximal number of nucleotide substitutions is 46 when St. Maries and FL strains were compared. Similarly, there are 44 substitutions in Omp9 when comparing the St. Maries and S. Idaho strains. In Omp14, there are 38 substitutions between Washington-Okanogan and S. Idaho. There are 17 substitutions in Omp13 when comparing the S. Idaho and Florida strains and 11 substitutions in Omp12 when comparing Oklahoma and S. Idaho. Consequently, this variation potentially limits these Omps as vaccine candidates.