Natalia Golender, Dan Gleser, Gabriel Kenigswald, Shani Scheinin, Eyal Klement
Background/Objectives: Bovine ephemeral fever virus (BEFV) causes an economically important arthropod-borne cattle disease. In 2023, a lineage I "Mayotte-like" (ML) strain emerged in Israel during an outbreak in vaccinated herds, raising concerns about its antigenic match with the live-attenuated vaccine based on Australian strain 919. We compared G-protein neutralizing sites and cross-neutralization among the vaccine strain, Israeli lineage IIIa strains from 2000 and 2021, and ML. Methods: G1-G3 neutralizing-site sequences were compared. Serum-neutralization assays tested all four viruses using sera from 87 cattle across five vaccination/exposure groups. Log2-transformed titers were compared within animals. Results: ML differed from the vaccine strain at eight amino acid positions within G1-G3, whereas the lineage IIIa strains differed from the vaccine strain at three or four positions. In vaccinated, unexposed calves, neutralizing titers against the vaccine and 2021 strains were 4.0- and 2.7-fold higher, respectively, than against ML (both p < 0.01). In unvaccinated 2021-exposed cattle, titers against the 2021 strain were 6.5-fold higher than against ML (p < 0.01). In unvaccinated 2023-exposed cattle, titers against ML were 4.76-fold higher than against the vaccine strain (p < 0.01). Between-strain differences were smaller in vaccinated 2023-exposed cattle. Conclusions: Sequence divergence and cross-neutralization indicate a markedly reduced antigenic match between the Australian 919 vaccine strain and the ML strain. Given the continued circulation and emergence of antigenically divergent BEFV strains and their potential for geographic spread, challenge and field-effectiveness studies are urgently needed to determine the clinical protection afforded by the current vaccine. Lineage-matched or multivalent vaccines should therefore be prioritized to broaden protection against circulating and newly emerging strains.