Sequence and immunologic conservation of Anaplasma marginale OmpA within strains from Ghana as compared to the predominant OmpA variant

Authors: FUTSE, JAMES - University Of Ghana; BUAMI, GRACE - University Of Ghana; KAYANG, BONIFACE - University Of Ghana; KOKU, ROBERTA - Washington State University; PALMER, GUY - University Of Washington; GRACA, TELMO - Washington State University; Noh, Susan

Submitted to: PLOS ONE
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 7/3/2019
Publication Date: 7/10/2019
Citation: Futse, J.E., Buami, G., Kayang, B.B., Koku, R., Palmer, G.H., Graca, T., Noh, S.M. 2019. Sequence and immunologic conservation of Anaplasma marginale OmpA within strains from Ghana as compared to the predominant OmpA variant. PLoS One. 14(7):e0217661. https://doi.org/10.1371/journal.pone.0217661.
DOI: https://doi.org/10.1371/journal.pone.0217661

Interpretive Summary: Bovine anaplasmosis, caused by Anaplasma marginale, is the most prevalent, production limiting disease of cattle worldwide. Prevention of this disease depends on the heavy use of acaricides which are expensive and only partially effective due to the necessity for frequent administration, particularly in tropical regions with heavy tick burdens. Consequently, vaccine development is a high priority for this disease. Due to the high degree of genetic diversity of this pathogen, the identification of effective cross-protective antigens has been challenging. Importantly, OmpA was recently shown to mediate binding between A. marginale and the host cells, thus making it a relevant vaccine candidate. With a few exceptions, the genetic variation of this pathogen in general and ompA specifically has predominantly been examined in North American strains. However, genetic variation tends to be greater in tropical regions with high pathogen prevalence and transmission pressure. In this work we found three variation of this gene in A. marginale infected cattle in Ghana, all of which were different from previously identified variants. In comparison, strains from all other geographic regions, except one, shared a single OmpA variant, Variant 1. Next, we determined that these sequences differences did not alter the ability of antibody to recognize the most common variant of OmpA. These findings support the value of OmpA as a potentially broadly protective vaccine candidate, which has the potential to improve the livelihoods of cattle producers worldwide.

Technical Abstract: 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.