Chimpanzee/human mAbs to vaccinia virus B5 protein neutralize vaccinia and smallpox viruses and protect mice against vaccinia virus.
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.
Chen
Zhaochun
Z
Hepatitis Viruses Section, Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, Office of Research Services, Office of the Director, National Institutes of Health, Bethesda, MD 20892, USA.
Earl
Patricia
P
Americo
Jeffrey
J
Damon
Inger
I
Smith
Scott K
SK
Zhou
Yi-Hua
YH
Yu
Fujuan
F
Sebrell
Andrew
A
Emerson
Suzanne
S
Cohen
Gary
G
Eisenberg
Roselyn J
RJ
Svitel
Juraj
J
Schuck
Peter
P
Satterfield
William
W
Moss
Bernard
B
Purcell
Robert
R
D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology* / Q000302:isolation & purification; D000939:Epitopes / Q000276:immunology; D005260:Female; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000276:immunology / Q000302:isolation & purification; D051379:Mice; D008969:Molecular Sequence Data; D009500:Neutralization Tests; D002679:Pan troglodytes / Q000276:immunology*; D014615:Vaccinia / Q000276:immunology* / Q000517:prevention & control*; D014616:Vaccinia virus / Q000737:chemistry / Q000276:immunology* / Q000472:pathogenicity; D012901:Variola virus / Q000276:immunology*; D014764:Viral Proteins / Q000737:chemistry / Q000276:immunology*
D000911:Antibodies, Monoclonal; D000939:Epitopes; D007140:Immunoglobulin Fab Fragments; D014764:Viral Proteins