An epitope conserved in orthopoxvirus A13 envelope protein is the target of neutralizing and protective antibodies

Primary immunization of humans with smallpox vaccine (live vaccinia virus (VACV)) consistently elicits antibody responses to six VACV virion membrane proteins, including A13. However, whether anti-A13 antibody contributes to immune protection against orthopoxviruses was unknown. Here, we isolated a murine monoclonal antibody (mAb) against A13 from a mouse that had been infected with VACV. The anti-A13 mAb bound to recombinant A13 protein with an affinity of 3.4 nM and neutralized VACV mature virions. Passive immunization of mice with the anti-A13 mAb protected against intranasal VACV infection. The epitope of the anti-A13 mAb was mapped to a 10-amino acid sequence conserved in all orthopoxviruses, including viriola virus and monkeypox virus, suggesting that anti-A13 antibodies elicited by smallpox vaccine might contribute to immune protection against orthopoxviruses. In addition, our data demonstrates that anti-A13 mAbs are effective for treating orthopoxvirus infection.