Isolation of a second recombinant human respiratory syncytial virus monoclonal antibody fragment (Fab RSVF2-5) that exhibits therapeutic efficacy in vivo.
A second human respiratory syncytial virus (RSV)-neutralizing monoclonal antibody was isolated and its binding site was identified. Fab F2-5 is a broadly reactive fusion (F) protein-specific recombinant Fab generated by antigen selection from a random combinatorial library displayed on the surface of filamentous phage. In an in vitro plaque-reduction test, the Fab RSVF2-5 neutralized the infectivity of a variety of field isolates representing viruses of both RSV subgroups A and B. The Fab recognized an antigenic determinant that differed from the only other human anti-F monoclonal antibody (RSV Fab 19) described thus far. A single dose of 4.0 mg of Fab RSVF2-5/kg of body weight administered by inhalation was sufficient to achieve a 2000-fold reduction in pulmonary virus titer in RSV-infected mice. The antigen-binding domain of Fab RSVF2-5 offers promise as part of a prophylactic regimen for RSV infection in humans.
Crowe
J E
JE
Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA. croweje@ctrvax.vanderbilt.edu
Gilmour
P S
PS
Murphy
B R
BR
Chanock
R M
RM
Duan
L
L
Pomerantz
R J
RJ
Pilkington
G R
GR
D000818:Animals; D000911:Antibodies, Monoclonal / Q000096:biosynthesis* / Q000276:immunology / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D000914:Antibodies, Viral / Q000032:analysis / Q000276:immunology; D000956:Antigens, Viral / Q000235:genetics / Q000276:immunology; D005260:Female; D015707:HN Protein; D007140:Immunoglobulin Fab Fragments / Q000235:genetics / Q000276:immunology; D008168:Lung / Q000821:virology; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D009500:Neutralization Tests; D016133:Polymerase Chain Reaction; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology*; D018357:Respiratory Syncytial Virus Infections / Q000276:immunology* / Q000517:prevention & control; D018113:Respiratory Syncytial Virus, Human / Q000235:genetics / Q000276:immunology*; D017422:Sequence Analysis, DNA; D013047:Specific Pathogen-Free Organisms; D014759:Viral Envelope Proteins; D014764:Viral Proteins / Q000235:genetics / Q000276:immunology*
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000914:Antibodies, Viral; D000956:Antigens, Viral; D015707:HN Protein; D007140:Immunoglobulin Fab Fragments; C101293:RSHZ19 monoclonal antibody; D011993:Recombinant Fusion Proteins; D014759:Viral Envelope Proteins; D014764:Viral Proteins; C116204:attachment protein G