Biological activity, binding site and affinity of monoclonal antibodies to the fusion protein of respiratory syncytial virus.
The neutralizing activity and fusion-inhibition activity per unit weight of immunoglobulin were determined for each of a panel of 20 monoclonal antibodies (MAbs) to the fusion (F) protein of respiratory syncytial (RS) virus. Neutralization did not correlate with fusion-inhibiting activity, suggesting that the F protein plays at least two independent, antibody-sensitive roles in viral infection. Antibodies with the highest biological activity against A2, a subgroup A strain of RS virus, neutralized a subgroup B strain (8/60) poorly, suggesting a degree of antigenic variation that may be important in human infection. All but one fusion-inhibiting MAb bound to protein blots and binding was mapped to two areas on overlapping F protein fragments. One MAb with relatively poor fusion-inhibiting activity bound only to fragments C-terminal of amino acid 384, the remainder bound only to fragments containing residues 253 to 289. MAbs directed to the latter site were heterogeneous in neutralizing activity, subgroup specificity and fusion-inhibiting activity. These variations between MAbs could not be accounted for by differences in their binding avidities. We suggest that this binding site is not the complete antibody epitope which probably includes conformation-dependent elements.
West
W H
WH
Division of Virology, University of Newcastle upon Tyne, U.K.
Lounsbach
G R
GR
Bourgeois
C
C
Robinson
J W
JW
Carter
M J
MJ
Crompton
S
S
Duhindan
N
N
Yazici
Z A
ZA
Toms
G L
GL
D000818:Animals; D000911:Antibodies, Monoclonal / Q000378:metabolism* / Q000494:pharmacology; D001666:Binding Sites, Antibody; D004797:Enzyme-Linked Immunosorbent Assay; D051379:Mice; D008807:Mice, Inbred BALB C / Q000276:immunology; D009500:Neutralization Tests; D011993:Recombinant Fusion Proteins / Q000032:analysis / Q000276:immunology / Q000378:metabolism; D012136:Respiratory Syncytial Viruses / Q000378:metabolism*; D014760:Viral Fusion Proteins / Q000032:analysis / Q000276:immunology / Q000378:metabolism*
D000911:Antibodies, Monoclonal; D011993:Recombinant Fusion Proteins; D014760:Viral Fusion Proteins