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 weig ht of immunoglobulin were determined for each of a panel of 20 monoclo nal antibodies (MAbs) to the fusion (F) protein of respiratory syncyti al (RS) virus. Neutralization did not correlate with fusion-inhibiting activity, suggesting that the F protein plays at least two independen t, antibody-sensitive roles in viral infection. Antibodies with the hi ghest 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 mapp ed to two areas on overlapping F protein fragments. One MAb with relat ively poor fusion-inhibiting activity bound only to fragments C-termin al of amino acid 384, the remainder bound only to fragments containing residues 253 to 289. MAbs directed to the latter site were heterogene ous in neutralizing activity, subgroup specificity and fusion-inhibiti ng activity. These variations between MAbs could not be accounted for by differences in their binding avidities. We suggest that this bindin g site is not the complete antibody epitope which probably includes co nformation-dependent elements.