A neutralizing antibody protects Kunming mice against AKAV lethal challenge.

Abstract

BACKGROUND: Akabane virus (AKAV) infection is associated with arthrogryposis-hydranencephaly syndrome in ruminants. Current commercialized AKAV live attenuated vaccines have safety concerns and cannot fully protect against all genotypes or emerging strains. Thus, developing a new type of vaccine or treatment is urgently required. The neutralizing antibodies (NAbs) directed against the Gc protein can efficiently neutralize the correspondingviruses. We previously generated three NAbs against the Gc protein of AKAV that collectively recognize a highly conserved epitope among diverse AKAV genotypes and established a mouse model of AKAV infection. Here, our objective was to evaluate the protective efficacy of one of the produced NAbs, 4F12, against AKAV infection using the mouse model. METHODS: Suckling Kunming mice were first intraperitoneally administered varying doses of the NAb 4F12, followed by intraperitoneal (IP) or intracerebral (IC) challenge with a lethal dose of AKAV. Clinical symptoms, body weight, and mortality were then monitored and recorded daily for 14 days. The AKAV RNA, viral particles, antigens distribution, and microscopic lesions in the brain tissues of the experimental mice were analyzed. RESULTS: All mice that did not receive 4F12 pretreatment died before the experimental endpoint, regardless of the AKAV challenge routes. While a dose-dependent survival increase (50% ~ 83.33%) was observed in 4F12-pretreated mice, with higher antibody concentrations conferring greater protection against both IC and IP AKAV challenges. Moreover, all mice that survived AKAV challenge due to 4F12 pretreatment showed complete absence of AKAV RNA, viral particles, and antigens in brain tissues, with no detectable virus-associated brain lesions. CONCLUSIONS: We proved that the NAb 4F12 could reduce the AKAV-induced mortality in mice. 4F12 is a promising candidate suitable for clinical development as an AKAV therapeutic. The highly conserved epitope recognized by 4F12 provides critical insights for the design of new broadly protective AKAV vaccines.