The development and validation of a novel nanobody-based competitive ELISA for the detection of foot and mouth disease 3ABC antibodies in cattle

Authors: GELKOP, SIGAL - Ben Gurion University Of Negev; SOBARZO, ARIEL - Ben Gurion University Of Negev; BRANGEL, POLINA - University College London; VINCKE, CECILE - Vrije University; ROMAO, E - Vrije University; FEDIDA-METULA, SHLOMIT - University College London; STROM, NICK - Kimron Veterinary Institute; ATALIBA, IRENE - Uganda Virus Research Institute; MWIIN, FRANK - Makerere University; OCHWO, SYLVESTER - Makerere University; VELAZQUEZ-SALINAS, LAURO - Oak Ridge Institute For Science And Education (ORISE); MCKENDRY, RACHEL - University College London; MUYLDERMANS, SERGE - Uganda Virus Research Institute; LUTWAMA, JULIUS - Uganda Virus Research Institute; Rieder, Aida - Elizabeth; YAVELSKY, VICTORIA - University College London; LOBEL, LESLIE - Ben Gurion University Of Negev

Submitted to: Frontiers in Veterinary Science
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 9/19/2018
Publication Date: 10/12/2018
Citation: Gelkop, S., Sobarzo, A., Brangel, P., Vincke, C., Romao, E., Fedida-Metula, S., Strom, N., Ataliba, I., Mwiin, F.N., Ochwo, S., Velazquez-Salinas, L., McKendry, R.A., Muyldermans, S., Lutwama, J.J., Rieder, A.E., Yavelsky, V., Lobel, L. 2018. The development and validation of a novel nanobody-based competitive ELISA for the detection of foot and mouth disease 3ABC antibodies in cattle. Frontiers in Veterinary Science. https://doi.org/10.3389/fvets.2018.00250.
DOI: https://doi.org/10.3389/fvets.2018.00250

Interpretive Summary: Foot-and-Mouth Disease (FMD) is a highly contagious disease of livestock animals, which causes devastating economic losses across many parts of the world. In this study we used camels to produce antibodies known as “nanobodies” against FMD virus (FMDV) proteins. Camels make antibodies that are very useful for developing diagnostic tests due to the fact that they are very specific to a particular protein and do not cross react easily with others. This manuscript describes the development of a novel diagnostic assay based on these nanobodies. This novel assay proved very effective at detecting cattle exposed to FMD in Uganda and could benefit FMD control measures in sub-Saharan Africa.

Technical Abstract: Effective control management of foot and mouth disease (FMD) requires diagnostic tests to distinguish infected from vaccinated animals (DIVA). To address this need, several enzyme-linked immunosorbent assay (ELISA) platforms have been developed, however these tests vary in their sensitivity and specificity and are very expensive for developing countries. Camelid-derived single-domain antibodies fragments so-called Nanobodies, have demonstrated great efficacy for the development of serological diagnostics. This study describes the development of a novel nanobody-based FMD 3ABC competitive ELISA, for the serological detection of antibodies against FMD Non-Structural Proteins (NSP) in Ugandan cattle herds. This in-house ELISA was validated using more than 600 seram from different Uganda districts, and virus serotype specificities. The evaluation of the performance of the assay demonstrated high diagnostic sensitivity and specificity, of 94% (95 % CI: 88.9–97.2) and 97.67 % (95 % CI: 94.15–99.36), respectively, as well as the capability to detect NSP-specific antibodies against multiple FMD serotype infections. Comparison with the commercial prioCHECK FMDV NSP-FMD test, demonstrated a strong concordance and high agreement in the performance of the two tests, with a kappa coefficient of 0.875. This developed Nanobody-based FMD 3ABC competitive ELISA could clearly benefit routine disease diagnosis, establishment of disease-free zones, and the improvement of FMD management and control in endemically complex environments such as found in Africa.