Expression of the F glycoprotein of respiratory syncytial virus by a recombinant vaccinia virus: comparison of the individual contributions of the F and G glycoproteins to host immunity.

Abstract

A cDNA clone representing the mRNA coding sequence of the fusion glycoprotein (F) gene of human respiratory syncytial virus (RSV) was constructed and inserted into the thymidine kinase gene of vaccinia virus (WR strain) under the control of a vaccinia virus promoter. The resulting recombinant vaccinia virus, vaccinia F, expressed the F1 and F2 cleavage products (48 and 20 kDa, respectively) of the F glycoprotein in cell culture. F1 and F2 were indistinguishable from their authentic RSV counterparts with respect to glycosylation, disulfide linkage, electrophoretic mobility, cellsurface expression, and antigenic specificity. Cotton rats infected intradermally with vaccinia F developed a high titer of serum F-specific antibodies, which neutralized infectivity of RSV. This neutralizing antibody response exceeded that induced by infection of the respiratory tract with RSV and was 6-fold higher than that induced by vaccinia G, a recombinant vaccinia virus that expressed the RSV G glycoprotein gene. Immunization with vaccinia F stimulated almost complete resistance to replication of RSV in the lower respiratory tract as well as significant resistance in the upper respiratory tract.

Antigenic and immunogenic analysis of group A and group B respiratory syncytial virus G proteins expressed from recombinant baculoviruses

“…These results were in agreement with previous studies of G protein immunogenicity. Vaccinia virus recombinants expressing the G protein provide cotton rats with a significant protection against challenge by live RS virus (Olmsted et al, 1986;Stott et al, 1986), as does immunoatfinity-purified G protein (Walsh et al, 1987). Thus, although not compared directly in these experiments, the baculovirus-expressed G proteins appeared to have immunogenic similarities to the mammalian cellexpressed G proteins.…”

Inhibition of fusion by neutralizing monoclonal antibodies to the haemagglutinin-neuraminidase glycoprotein of Newcastle disease virus

“…Evidence from a number of recent studies suggests that HN, in addition to F protein, is required for the induction of fusion by paramyxoviruses (Sakai & Shibuta, 1989;Ebata et al, 1991 ;Morrison et al, 1991 ;Moscona & Peluso, 199 I), although there is also evidence to the contrary (Markwell et al, 1985;Paterson et al, 1985;Olmstead et al, 1986;Alkhatib et al, 1990). The reasons for the discrepancy in the findings of these groups is unclear, but our data are consistent with H N being required for the induction of cell fusion and apparently for more than merely bringing the two membranes into close proximity to one another.…”

Effect of maternal antibody on IgA antibody response in nasopharyngeal secretion in infants and children during primary respiratory syncytial virus infection

“…Both immunological immaturity and immunosuppression mediated by maternally derived antibodies are presumed to be responsible for the poor immune response of the young infants (Parrott et al, 1973;Murphy et al, 1986 a, b). However, the mechanism of such immunomodulation in the respiratory tract during RSV infection remains to be defined.…”

“…The recombinant viruses and the vaccinia virus were inoculated at a multiplicity of 0"5. These viruses were kindly provided by Dr R. A. Olmsted (NIH) (Olmsted et al, 1986).…”