Identification and characterization of a human monoclonal antibody that potently neutralizes a broad panel of rabies virus isolates.
Rabies is a zoonosis that results in millions of human exposures worldwide each year. Human monoclonal antibodies (HuMAbs) that neutralize rabies virus may represent one viable strategy for post-exposure prophylaxis in humans, and have many advantages over current human or equine rabies immune globulin. Transgenic mice carrying human immunoglobulin genes were used to isolate human monoclonal antibodies that neutralized rabies virus. Several HuMAbs were identified that neutralized rabies virus variants from a broad panel of isolates of public health significance. HuMAb 17C7 was the most promising antibody identified because it neutralized all rabies virus isolates tested. HuMAb 17C7 recognizes a conformational epitope on the rabies virus glycoprotein which includes antigenic site III. HuMAb 17C7 protected hamsters from a lethal dose of rabies virus in a well-established in vivo model of post-exposure prophylaxis.
Sloan
Susan E
SE
Massachusetts Biologic Laboratories, University of Massachusetts Medical School, 305 South Street, Jamaica Plain, MA 02130, United States.
Hanlon
Cathleen
C
Weldon
William
W
Niezgoda
Michael
M
Blanton
Jesse
J
Self
Josh
J
Rowley
Kirk J
KJ
Mandell
Robert B
RB
Babcock
Gregory J
GJ
Thomas
William D
WD
Rupprecht
Charles E
CE
Ambrosino
Donna M
DM
D000818:Animals; D000911:Antibodies, Monoclonal / Q000235:genetics / Q000276:immunology / Q000494:pharmacology*; D002460:Cell Line; D006224:Cricetinae; D006023:Glycoproteins / Q000276:immunology; D006801:Humans; D016056:Immunodominant Epitopes / Q000235:genetics / Q000276:immunology; D012889:Mephitidae; D008647:Mesocricetus; D051379:Mice; D008822:Mice, Transgenic; D011818:Rabies / Q000276:immunology / Q000517:prevention & control; D011820:Rabies virus / Q000235:genetics / Q000276:immunology*; D014764:Viral Proteins / Q000276:immunology
D000911:Antibodies, Monoclonal; D006023:Glycoproteins; D016056:Immunodominant Epitopes; D014764:Viral Proteins