TYPE Original Research PUBLISHED 25 August 2022 DOI 10.3389/fvets.2022.913046 OPEN ACCESS EDITED BY Maureen T. Long, University of Florida, United States REVIEWED BY Francisco Rivera-Benítez, Instituto Nacional de Investigaciones Forestales, Agrícolas y Pecuarias (INIFAP), Mexico Semmannan Kalaiyarasu, ICAR-National Institute of High Security Animal Diseases (ICAR-NIHSAD), India *CORRESPONDENCE Sandra Belij-Rammerstorfer sandra.belij-rammerstorfer@ndm.ox.ac.uk Georgina Limon georgina.limon-vega@pirbright.ac.uk † These authors have contributed equally to this work and share first authorship ‡ These authors have contributed equally to this work and share last authorship SPECIALTY SECTION This article was submitted to Veterinary Infectious Diseases, a section of the journal Frontiers in Veterinary Science RECEIVED 05 April 2022 ACCEPTED 20 July 2022 PUBLISHED 25 August 2022 Development of anti-Crimean-Congo hemorrhagic fever virus Gc and NP-specific ELISA for detection of antibodies in domestic animal sera Sandra Belij-Rammerstorfer 1 * † , Georgina Limon 2 * † , Emmanuel A. Maze 2 , Kayleigh Hannant 2 , Ellen Hughes 3 , Simona R. Tchakarova 4 , Tsviatko Alexandrov 4 , Blandina T. Mmbaga 5,6 , Brian Willett 3 , George Booth 2 , Nicholas A. Lyons 2 , Natalie Baker 7 , Kelly M. Thomas 7 , Daniel Wright 1 , Jack Saunders 1 , Clare Browning 2 , Ginette Wilsden 2 , Miles Carroll 8 , Roger Hewson 7,9 , Bryan Charleston 2‡ , Teresa Lambe 1‡ and Anna B. Ludi 2‡ 1 Nuffield Department of Medicine, The Jenner Institute, University of Oxford, Oxford, United Kingdom, 2 The Pirbright Institute, Woking, United Kingdom, 3 Medical Research Council (MRC)-University of Glasgow Centre for Virus Research (CRV), Glasgow, United Kingdom, 4 Bulgarian Food Safety Agency, Sofia, Bulgaria, 5 Kilimanjaro Clinical Research Institute (KCRI), Kilimanjaro Christian Medical Centre, Moshi, Tanzania, 6 Kilimanjaro Christian Medical University College, Moshi, Tanzania, 7 Research and Evaluation, UK Health Security Agency, Porton Down, United Kingdom, 8 Pandemic Science Institute, Wellcome Centre for Human Genetics, Nuffield Department of Medicine, Oxford University, Oxford, United Kingdom, 9 Department of Infection Biology, London School of Hygiene and Tropical Medicine, London, United Kingdom Crimean-Congo hemorrhagic fever (CCHF) is a priority emerging disease. CCHF, caused by the CCHF virus (CCHFV), can lead to hemorrhagic fever in humans with severe cases often having fatal outcomes. CCHFV is maintained within a tick-vertebrate-tick cycle, which includes domestic animals. Domestic animals infected with CCHFV do not show clinical signs of the disease and the presence of antibodies in the serum can provide evidence of their exposure to the virus. Current serological tests are specific to either one CCHFV antigen or the whole virus antigen. Here, we present the development of two in-house ELISAs for the detection of serum IgG that is specific for two different CCHFV antigens: glycoprotein Gc (CCHFV Gc) and nucleoprotein (CCHFV NP). We demonstrate that these two assays were able to detect anti-CCHFV Gc-specific and anti-CCHFV NP-specific IgG in sheep from endemic CCHFV areas with high specificity, providing new insight into the heterogeneity of the immune response induced by natural infection with CCHFV in domestic animals. KEYWORDS Crimean-Congo hemorrhagic fever, ELISA, domestic animals, antibody response, CCHFV Gc, CCHFV NP Frontiers in Veterinary Science 01 frontiersin.org