Monoclonal antibodies demonstrate heterogeneity in the G glycoprotein of prototype strains and clinical isolates of respiratory syncytial virus

Abstract

In order to study variation among prototype strains and clinical isolates of respiratory syncytial (RS) virus, four prototype strains (Long, A2, CH18537, 9320) were used to produce monoclonal antibodies to this virus. The majority of monoclonals reacted with all four prototype strains by fluorescent antibody staining. Among the non-cross-reacting monoclonals, five additional patterns of reactivity with the prototype strains were recognized. Fourteen monoclonals, including ones representative of each of the patterns of reactivity with the prototype strains, were selected to use for typing prototype strains and community isolates. All 14 were found by immunoprecipitation to recognize the RS virus G glycoprotein. These monoclonals could uniquely identify each of the prototype strains. In addition to the antigenic differences among the prototype strains detected by the monoclonals, differences were also detected in the migration of the G glycoprotein of the prototype strains in polyacrylamide gel electrophoresis. Fluorescent antibody staining with panels of monoclonals distinguished two antigenic types among 114 isolates of RS virus recovered from children in St. Louis during the period 1981-86. The predominant type (80% of isolates) had a pattern of reactivity that resembled but differed from that of either the Long or A2 strains. The second type had a pattern of reactivity identical with that of 9320. The possible significance of this heterogeneity must be considered in developing diagnostic tests as well as active or passive immunotherapy for infections caused by RS virus.

Antigenic structure of the human respiratory syncytial virus G glycoprotein and relevance of hypermutation events for the generation of antigenic variants.

“…a-Barreno et al, 1989) and in the present work, it is unclear why antibodies with restricted reactivity were preferentially isolated when Long virus was used as immunogen. The proportion of anti-G antibodies recognizing either of the three epitope categories is also different among those reported by other laboratories (Anderson et al, 1985 ;Stoch & Park, 1987). It is possible that the immunizing strain determines, at least in part, the predominant epitope category recognized by the MAbs but this possibility remains to be tested.…”

Molecular epidemiology of human respiratory syncytial virus in Uruguay: 1985-2001 - A review

“…A wide predominance of HRSV group A strain circulation was observed during the 17 consecutive periods analyzed, in agreement with most of the previous reports. In some countries where both groups co-circulated, group A was always predominant (Storch & Park 1987, Morgan et al 1987, Carballal et al 2000.…”

Monoclonal antibody neutralization escape mutants of respiratory syncytial virus with unique alterations in the attachment (G) protein.

“…The G protein carries several MAb-defined neutralizing epitopes (Walsh et al, 1989 ;Anderson et al, 1985 ;Storch & Park, 1987). The majority of neutralizing MAbs to G are group specific and even polyclonal antibodies to G demonstrate only minimal group cross-reactivity, suggesting that this common region is not immunodominant (Walsh et al, 1987).…”