Smallpox vaccine-induced antibodies are necessary and sufficient for protection against monkeypox virus

Vaccination with live vaccinia virus affords long- lasting protection against variola virus, the agent of smallpox. Its mode of protection in humans, however, has not been clearly defined. Here we report that vaccinia- specific B-cell responses are essential for protection of macaques from monkeypox virus, a variola virus ortholog. Antibody- mediated depletion of B cells, but not CD4(+) or CD8(+) T cells, abrogated vaccine- induced protection from a lethal intravenous challenge with monkeypox virus. In addition, passive transfer of human vaccinia-neutralizing antibodies protected nonimmunized macaques from severe disease. Thus, vaccines able to induce long- lasting protective antibody responses may constitute realistic alternatives to the currently available smallpox vaccine (Dryvax).