Smallpox (variola virus) is a bioweapon concern.
Monkeypox is a growing zoonotic poxvirus threat. These problems have resulted in extensive efforts to develop potential
therapeutics that can prevent or treat potentially lethal
poxvirus infections in humans.
Monoclonal antibodies (mAbs) against
smallpox are a conservative approach to this problem, as the licensed human
smallpox vaccine (vaccinia virus, VACV) primarily works on the basis of protective antibody responses against
smallpox. Fully human mAbs (hmAbs) against
vaccinia H3 (H3L) and B5 (B5R), targeting both the mature virion (MV) and extracellular enveloped virion (EV) forms, have been developed as potential
therapeutics for use in humans. Post-exposure prophylaxis was assessed in both murine and rabbit animal models. Therapeutic efficacy of the mAbs was assessed in three good laboratory practices (GLP) studies examining
severe combined immunodeficiency mice (SCID) given a lethal VACV
infection. Pre-exposure combination hmAb
therapy provided significantly better protection against disease and death than either single hmAb or
vaccinia immune globulin (VIG). Post-exposure combination mAb
therapy provided significant protection against disease and death, and appeared to fully cure the VACV
infection in ≥50% of SCID mice. Therapeutic efficacy was then assessed in two rabbit studies examining post-exposure hmAb prophylaxis against rabbitpox (RPXV). In the first study, rabbits were infected with RPVX and then provided hmAbs at 48 hrs post-
infection, or 1 hr and 72 hrs post-
infection. Rabbits in both groups receiving hmAbs were 100% protected from death. In the second rabbitpox study, 100% of animal treated with combination hmAb
therapy and 100% of animals treated with anti-B5 hmAb were protected. These findings suggest that combination hmAb treatment may be effective at controlling
smallpox disease in immunocompetent or immunodeficient humans.