Monoclonal Antibodies Against Orthopoxviruses

Concerns that variola (smallpox) virus might be used as a biological weapon have led to the recommendation of widespread vaccination with vaccinia virus. While vaccination is generally safe and effective for prevention of smallpox, it is well documented that various adverse reactions in individuals have been caused by vaccination with existing licensed vaccines. Vaccinia immune globulin (VIG) prepared from vaccinated humans has historically been used to treat adverse reactions arising from vaccinia immunization. However, VIG lots may have different potencies and carry the potential to transmit other viral agents.

Chimpanzee Fabs against the B5 and A33 outer extracellular membrane proteins of vaccinia virus were isolated and converted into complete mAbs with human gamma1 heavy chain constant regions. The two mAbs displayed high binding affinities to B5 and A33. The mAbs inhibited the spread of vaccinia virus as well as variola virus (the causative agent of smallpox) in vitro, protected mice from subsequent intranasal challenge with virulent vaccinia virus, protected mice when administered 2 days after challenge, and provided significantly greater protection than that afforded by VIG.