Cross-neutralization activities of antibodies against 18 lyssavirus glycoproteins

Some lyssaviruses, including the rabies virus (RABV), induce lethal neurological symptoms in humans. However, commercial vaccines have only been evaluated for their efficacy against RABV and not against other lyssaviruses. To assess cross-reactivity among lyssaviruses, including RABV, sera from rabbits inoculated with human and animal RABV vaccines and polyclonal antibodies from rabbits immunized with expression plasmids of the glycoproteins of all 18 lyssaviruses were prepared, and cross-reactivity was evaluated via virus-neutralization tests using RABV, European bat lyssavirus-1 (EBLV-1), Duvenhage virus (DUVV), Mokola virus (MOKV), and Lagos bat virus (LBV). The sera against RABV vaccines showed cross-reactivity with EBLV-1 and DUVV, which both belong to phylogroup I. However, the reactivity with MOKV and LBV in phylogroup II was notably limited or below the detection level. Next, we compared the cross-reactivity of the polyclonal antibodies against all the lyssavirus glycoproteins. Polyclonal antibodies had high virus-neutralization titers against the same phylogroup, but not against different phylogroups. Our findings indicate that a new vaccine should be developed for pre- and post-exposure prophylaxis against lyssavirus infections.