Protection of mice from fatal measles encephalitis by vaccination with vaccinia virus recombinants encoding either the hemagglutinin or the fusion protein.

Abstract

Vaccinia virus recombinants encoding the hemagglutinin or fusion protein of measles virus have been constructed. Infection of cell cultures with the recombinants led to the synthesis of authentic measles proteins as judged by their electrophoretic mobility, recognition by antibodies, glycosylation, proteolytic cleavage, and presentation on the cell surface. Mice vaccinated with a single dose of the recombinant encoding the hemagglutinin protein developed antibodies capable of both inhibiting hemagglutination activity and neutralizing measles virus, whereas animals vaccinated with the recombinant encoding the fusion protein developed measles neutralizing antibodies. Mice vaccinated with either of the recombinants resisted a normally lethal intracerebral inoculation of a cell-associated measles virus subacute sclerosing panencephalitis strain.

Efficacy of individual measles virus structural proteins in the protection of rats from measles encephalitis

“…These data confirm the results of the protection experiments carried out in mice with VVF and VVH (Drillien et al, 1988) and VVN in rats (Bankamp et al, 1991). The data presented in this paper extend our previous knowledge of the effect of the immune response against the M and P proteins of MV.…”

“…Experiments published previously suggested that recombinant VVs expressing the H and F glycoproteins of MV confer protective immunity in mice via induction of high levels of virus-neutralizing and/or fusioninhibiting antibodies (Drillien et al, 1988). It was claimed that the humoral immune response is essential for the observed protection.…”

“…However, blocking macrophage invasion into the CNS across the blood-brain barrier prevented clinical symptoms and reduced histopathological lesions (Huitinga et al, 1990). Antiviral neutralizing antibodies are apparently instrumental in overcoming CNS infection after immunization with VVH (Drillien et al, 1988;Malvoisin & Wild, 1990). The effect of T cells induced by VVH immunization in the absence of virus-neutralizing antibodies is uncertain.…”

“…The recombinants are referred to as VVN, VVP and VVM, expressing the N, P and M proteins respectively. The VVH and VVF recombinants cloned from the Hall6 isolate of MV which differs from the Edmonston isolate by only a few amino acids (B. K. Rima &K. Baczko, personal communication) were obtained from R. Drillien, Strasbourg, France (Drillien et al, 1988). The expression of the inserted MV genes was analysed by immunoprecipitation, immunofluorescence or Western blotting as described previously (Bankamp et at., 1991).…”

“…Recently, it has been shown that immunization of mice with recombinant vaccinia viruses (VV) expressing MV H and F proteins or rats immunized with VV expressing MV N protein were protected from measles infection (Drillien et al, 1988;Bankamp et al, 1991). In an extension of these observations the present study compares the ability and efficacy of all MV structural proteins except the L protein to evoke a protective immune response against MV infection in an animal model using VV recombinants expressing individual MV proteins.…”