To study the antigenic characteristics of respiratory syncytial virus (RSV), we developed and evaluated monoclonal antibodies (MAbs) to three strains of RSV: 11 to Long, 4 to 18537, and 9 to A2. Six of these MAbs immunoprecipitated the nucleoprotein, six the large glycoprotein, and 11 the fusion protein. By the pattern of the reactions of these MAbs to 16 strains of RSV in an indirect immunofluorescence assay or enzyme-linked immunosorbent assay, we were able to distinguish three subgroups. With a panel of 10 of these 24 MAbs, we tested 26 strains isolated between 1979 and 1982 in Boston and found that 22 belonged to group 1, 4 to group 2, and none to group 3. The pattern of the reactions of the MAbs against representative strains from the three groups identified nine epitopes by indirect immunofluorescence assay: three of each on the nucleoprotein, the large glycoprotein, and the fusion protein. These results, along with those of previous studies, suggest that groups 1 and 3 are antigenically similar and group 2 is antigenically more distinct.

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Respiratory syncytial virus (RSV) is considered to be of a single serotype. Antigenic variants are detectable both by neutralization and monoclonal antibodies and have been divided into two broad categories, groups 1 and 2. Group 2 isolates have been considered to be uncommon. We used indirect immunofluorescence with strain-specific monoclonal antibodies to study RSV isolates from hospitalized infants in the greater Boston area. Of 223 RSV isolates recovered over a five-month period in 1983-1984, 125 (56%) were group 1, 92 (41%) were group 2, and 6 (3%) were of an intermediate character. Among 181 community-acquired RSV isolates, both temporal and geographic clustering was observed: group 1 isolates were common from January through March and predominated in central Boston; group 2 isolates were found principally in February and were acquired in outlying, particularly northern, areas. Strain-specific differences were not found with respect to sex, age, or clinical findings. An analysis of 82 RSV isolates from the 1981-1982 season showed 75 (91%) group 1 isolates and 7 (9%) group 2 isolates. We conclude that at least two antigenically distinct groups of RSV isolates may circulate concurrently in the community and that the prevalence of group 2 isolates appears greater than previously suspected.

SUMMARYThe synthesis of the two respiratory syncytial (RS) virus glycoproteins (VP66 and VP84) was examined under standard conditions and after treatment with tunicamycin and monensin. The protein backbone for VP66, the fusion protein (F1,2) is cotranslationally glycosylated to form F0, which is cleaved to form F1, 2 by 20 min of chase. Monensin treatment inhibited the cleavage of Fo over an 80 min chase period, indicating that this occurred late in the transit of Fo through the Golgi apparatus or after exit from the Golgi apparatus. Tunicamycin treatment resulted in the synthesis of a 50K to 55K unglycosylated F0 which is cleaved to a 40K protein. VP84, the large glycoprotein, contains a protein backbone of only 26K to 30K which is modified by Nlinked and probable O-linked glycosylation. Tunicamycin treatment results in the synthesis of a 70K protein (p70) which incorporates [3H]glucosamine and [3H]fucose but not [3H]mannose. Glycosylated precursors varying in tool. wt. from 29K to 45K (p45) are found in infected cells at regular 2K to 3K intervals, producing a 'ladder' effect. The step from p45 to VP84 is severely delayed by monensin treatment thereby enhancing the 'ladder' effect of the precursors.

The administration of rgp160 was well tolerated and safe, resulted in a high rate of antibody response by Western blot after the administration of the third and fourth doses, and generated serum neutralizing activity and complement-mediated antibody-dependent enhancement in some subjects after the fourth dose.