Anaplasma marginale outer membrane protein vaccine candidates are conserved in North American and South African strains

Authors: HOVE, P - University Of Pretoria; BRAYTON, K - Washington State University; LIENBENBERG, J - Onderstepoort Veterinary Institute; PRETORIUS, ALRI - Onderstepoort Veterinary Institute; OOSTHUIZEN, MARINDA - University Of Pretoria; Noh, Susan; COLLINS, N - University Of Pretoria

Submitted to: Ticks and Tick Borne Diseases
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 4/16/2020
Publication Date: 4/18/2020
Citation: Hove, P., Brayton, K.A., Lienbenberg, J., Pretorius, A., Oosthuizen, M.C., Noh, S.M., Collins, N.E. 2020. Anaplasma marginale outer membrane protein vaccine candidates are conserved in North American and South African strains. Ticks and Tick Borne Diseases. 11(4). https://doi.org/10.1016/j.ttbdis.2020.101444.
DOI: https://doi.org/10.1016/j.ttbdis.2020.101444

Interpretive Summary: One of the major limitations in vaccine development to prevent bovine anaplasmosis is identifying vaccine targets that are broadly conserved across disparate geographic areas thus allowing for a single vaccine that protects against all strains of A. marginale. Using reverse genetics and proteomics, a variety of outer membrane proteins that serve as vaccine targets have been identified. However, the genetic variability of these candidates and whether or not the variability affects antibody binding, a major component of the protective immune response, is unknown. In this work, five genes encoding vaccine candidates were sequenced from cattle in S. Africa infected with diverse strains of A. marginale. Additionally the cross reactivity of the antibody response between North American and the South African strains of A. marginale was tested. Overall, there was high conservation of the genes with accompanying high conservation of the antibody response between strains. These data provide additional evidence that a cross protective vaccine against disparate A. marginale strains is possible, though additional work to identify the protective antigens and optimal formulation is required.

Technical Abstract: Bovine anaplasmosis is a globally economically important tick-borne disease caused by the obligate intraerythrocytic rickettsia, Anaplasma marginale. A live Anaplasma centrale blood-based vaccine is available, but it does not protect against all A. marginale field strains and may also transmit other blood-borne pathogens. Five potential outer membrane protein (OMP) vaccine candidates from North American A. marginale strains have been well-characterised in A. marginale strains from the USA, however, their levels of conservation in other countries must be ascertained in order to inform their use in a vaccine with regional or global efficacy. This study assessed the amino acid variation in vaccine candidate OMPs in South African strains of A. marginale, and also compared the immunogenic properties between South African and US strains. OMP genes Am779, Am854, omp7, omp8 and omp9 were amplified and sequenced from a set of genetically diverse South African samples with different msp1a-genotypes. OMPs Am854 and Am779 were highly conserved, with 99–100% amino acid identity, while Omp7, Omp8 and Omp9 had 79–100% identity with US strains. As has been shown previously, Omp7–9 possess conserved N- and C- termini, a central hypervariable region, and a highly conserved T-cell epitope, FLLVDDA(I/V)V, in the N-terminal region. Western analysis of recombinant OMPs indicates strong antigenic conservation between South African and US strains of A. marginale, suggesting that they are good candidates for use in a novel global vaccine cocktail, although further work on the best formulation and delivery methods will be necessary.