Prophylaxis with respiratory syncytial virus F-specific humanized monoclonal antibody delays and moderately suppresses the native antibody response but does not impair immunity to late rechallenge.
Respiratory syncytial virus (RSV) is the most significant viral cause of lower respiratory tract disease in infants and children. This study tested the hypothesis that a humanized murine monoclonal antibody (MAb) would protect against RSV infection in mice and have minimal suppressive effect upon the immune response because it is directed against a single epitope. A humanized murine MAb (RSHZ19) was tested for both prophylaxis and treatment of RSV infection in BALB/c mice and compared with a polyclonal product. Mice were rechallenged when passively administered antibody was undetectable (day 104). RSHZ19 reduced virus titer and protected against illness when used in prophylaxis and effected rapid virus clearance when used as treatment. Polyclonal antibody was also an effective prophylaxis but required 200 times the dose in total protein. Peak neutralizing antibody responses were delayed and somewhat suppressed in the prophylactically treated groups, but mice were protected against infection on rechallenge. Secondary antibody response to rechallenge in passively immunized mice was equal to that in untreated mice.
Fisher
R G
RG
Department of Pediatrics, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.
Johnson
J E
JE
Dillon
S B
SB
Parker
R A
RA
Graham
B S
BS
D000818:Animals; D000911:Antibodies, Monoclonal / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000917:Antibody Formation; D002648:Child; D005260:Female; D006801:Humans; D007116:Immunization, Passive; D007074:Immunoglobulin G; D007145:Immunoglobulin kappa-Chains; D007223:Infant; D008168:Lung / Q000821:virology; D051379:Mice; D008807:Mice, Inbred BALB C; D011993:Recombinant Fusion Proteins / Q000493:pharmacokinetics / Q000627:therapeutic use; D018357:Respiratory Syncytial Virus Infections / Q000276:immunology* / Q000517:prevention & control; D018113:Respiratory Syncytial Virus, Human / Q000276:immunology* / Q000302:isolation & purification / Q000502:physiology; D014407:Tumor Cells, Cultured; D014779:Virus Replication; D015431:Weight Loss
D000911:Antibodies, Monoclonal; D007074:Immunoglobulin G; D007145:Immunoglobulin kappa-Chains; D011993:Recombinant Fusion Proteins