Characterization of chimpanzee/human monoclonal antibodies to vaccinia virus A33 glycoprotein and its variola virus homolog in vitro and in a vaccinia virus mouse protection model.
Three distinct chimpanzee Fabs against the A33 envelope glycoprotein of vaccinia virus were isolated and converted into complete monoclonal antibodies (MAbs) with human gamma 1 heavy-chain constant regions. The three MAbs (6C, 12C, and 12F) displayed high binding affinities to A33 (K(d) of 0.14 nM to 20 nM) and may recognize the same epitope, which was determined to be conformational and located within amino acid residues 99 to 185 at the C terminus of A33. One or more of the MAbs were shown to reduce the spread of vaccinia virus as well as variola virus (the causative agent of smallpox) in vitro and to more effectively protect mice when administered before or 2 days after intranasal challenge with virulent vaccinia virus than a previously isolated mouse anti-A33 MAb (1G10) or vaccinia virus immunoglobulin. The protective efficacy afforded by anti-A33 MAb was comparable to that of a previously isolated chimpanzee/human anti-B5 MAb. The combination of anti-A33 MAb and anti-B5 MAb did not synergize the protective efficacy. These chimpanzee/human anti-A33 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 and other orthopoxvirus diseases.
Chen
Zhaochun
Z
Hepatitis Viruses Section, Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, NIH, 50 South Drive, MSC 8009, Bethesda, MD 20892, USA. zc20a@nih.gov
Earl
Patricia
P
Americo
Jeffrey
J
Damon
Inger
I
Smith
Scott K
SK
Yu
Fujuan
F
Sebrell
Andrew
A
Emerson
Suzanne
S
Cohen
Gary
G
Eisenberg
Roselyn J
RJ
Gorshkova
Inna
I
Schuck
Peter
P
Satterfield
William
W
Moss
Bernard
B
Purcell
Robert
R
D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000737:chemistry / Q000276:immunology* / Q000302:isolation & purification / Q000627:therapeutic use*; D000914:Antibodies, Viral / Q000737:chemistry / Q000276:immunology* / Q000302:isolation & purification / Q000627:therapeutic use*; D001835:Body Weight; D004195:Disease Models, Animal; D018604:Epitope Mapping; D006801:Humans; D007127:Immunoglobulin Constant Regions / Q000235:genetics; D007140:Immunoglobulin Fab Fragments / Q000235:genetics / Q000302:isolation & purification; D008562:Membrane Glycoproteins / Q000276:immunology; D051379:Mice; D008969:Molecular Sequence Data; D009500:Neutralization Tests; D002679:Pan troglodytes; D014615:Vaccinia / Q000276:immunology / Q000517:prevention & control*; D014616:Vaccinia virus / Q000276:immunology*; D012901:Variola virus / Q000276:immunology*; D014759:Viral Envelope Proteins / Q000276:immunology
C446940:A33R protein, Vaccinia virus; D000911:Antibodies, Monoclonal; D000914:Antibodies, Viral; D007127:Immunoglobulin Constant Regions; D007140:Immunoglobulin Fab Fragments; D008562:Membrane Glycoproteins; D014759:Viral Envelope Proteins