Chimpanzee/human mAbs to vaccinia virus B5 protein neutralize vaccinia and smallpox viruses and protect mice against vaccinia virus

Zhaochun Chen(National Institutes of Health), Patricia L. Earl(The University of Texas MD Anderson Cancer Center), Jeffrey L. Americo(National Institute of Allergy and Infectious Diseases), Inger K. Damon(Centers for Disease Control and Prevention), Scott K. Smith(Centers for Disease Control and Prevention), Yi‐Hua Zhou(National Institutes of Health), Fujuan Yu(National Institutes of Health), Andrew Sebrell(National Institutes of Health), Suzanne U. Emerson, Gary H. Cohen(University of Pennsylvania), Roselyn J. Eisenberg(University of Pennsylvania), Juraj Švitel(National Institutes of Health), Peter Schuck(National Institutes of Health), William C. Satterfield(The University of Texas MD Anderson Cancer Center), Bernard Moss(The University of Texas MD Anderson Cancer Center), Robert H. Purcell(National Institutes of Health)
Proceedings of the National Academy of Sciences
January 25, 2006
10.1073/pnas.0510598103
Cited by 108Open Access
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Abstract

Chimpanzee Fabs against the B5 envelope glycoprotein of vaccinia virus were isolated and converted into complete mAbs with human gamma 1 heavy chain constant regions. The two mAbs (8AH8AL and 8AH7AL) displayed high binding affinities to B5 (Kd of 0.2 and 0.7 nM). The mAb 8AH8AL 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 a previously isolated rat anti-B5 mAb (19C2) or by vaccinia immune globulin. The mAb bound to a conformational epitope between amino acids 20 and 130 of B5. These chimpanzee/human anti-B5 mAbs may be useful in the prevention and treatment of vaccinia virus-induced complications of vaccination against smallpox and may also be effective in the immunoprophylaxis and immunotherapy of smallpox.

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