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Poliovirus chimeras expressing sequences from the principal neutralization domain of human immunodeficiency virus
J F Dedieu1, J Ronco, S van der Werf
1Unité de Virologie Moléculaire (Centre National de la Recherche Scientifique UA 545), Institut Pasteur, Paris, France.
Sequences from the principal neutralization domain of human immunodeficiency virus type 1 (HIV-1) strain LAI or RF have been expressed in antigenic site 1 of the capsid of the Sabin strain of poliovirus type 1. A number of the resulting chimeras were viable. Viable variants bearing mutations within the insertion site spontaneously arose from several nonviable chimeras. In general, these mutations result in a decrease in positive charge in the substituted antigenic site 1. Two of the chimeras were genetically stable and have been further characterized. Both chimeras were neutralized by various HIV-1 neutralizing antibodies. In rabbits, both chimeras produced high levels of antibodies which react with HIV-1 gp120/160 in immunoprecipitation and enzyme-linked immunosorbent assays. One of the chimeras (HIV-1LAI) produced a significant but weak HIV-1 neutralizing response.
Sequences from the principal neutralization domain of human immunodeficiency virus type 1 (HIV-1) strain LAI or RF have been expressed in antigenic site 1 of the capsid of the Sabin strain of poliovirus type 1. A number of the resulting chimeras were viable. Viable variants bearing mutations within the insertion site spontaneously arose from several nonviable chimeras. In general, these mutations result in a decrease in positive charge in the substituted antigenic site 1. Two of the chimeras were genetically stable and have been further characterized. Both chimeras were neutralized by various HIV-1 neutralizing antibodies. In rabbits, both chimeras produced high levels of antibodies which react with HIV-1 gp120/160 in immunoprecipitation and enzyme-linked immunosorbent assays. One of the chimeras (HIV-1LAI) produced a significant but weak HIV-1 neutralizing response.