Attenuated Mengo virus as a vector for immunogenic human immunodeficiency virus type 1 glycoprotein 120.
Introduction of a sequence encoding 147 amino acids from human immunodeficiency virus type I (HIV-1) strain MN glycoprotein gp120 into the RNA genome of the stably attenuated Mengo virus strain vM16 yielded an infectious recombinant virus, vMLN450, which expressed the heterologous HIV-1 sequence along with the normal Mengo virus proteins. The HIV-1 gp120 sequence, fused to the amino terminus of the short, nonstructural Mengo virus leader polypeptide was recognized by a gp120 V3 loop-specific monoclonal antibody. When inoculated into mice, recombinant virus vMLN450 elicited a high-titer anti-HIV-1 antibody response as well as an HIV-1MN-specific cytotoxic cellular immune response. An anti-HIV-1 antibody response could also be detected in cynomolgus monkeys after a single immunization. We propose that attenuated Mengo virus can serve as an effective expression vector in cell systems and various animal species and offers another approach to the development of new, live recombinant vaccines.
Altmeyer
R
R
Unité de Virologie Moléculaire, Institut Pasteur, Paris, France.
Escriou
N
N
Girard
M
M
Palmenberg
A
A
van der Werf
S
S
D000595:Amino Acid Sequence; D000818:Animals; D000917:Antibody Formation; D001483:Base Sequence; D003602:Cytotoxicity, Immunologic; D017931:DNA Primers; D004797:Enzyme-Linked Immunosorbent Assay; D005822:Genetic Vectors; D016679:Genome, Viral; D015483:HIV Antibodies / Q000096:biosynthesis* / Q000097:blood; D015699:HIV Envelope Protein gp120 / Q000096:biosynthesis* / Q000276:immunology; D015497:HIV-1 / Q000235:genetics / Q000378:metabolism*; D008252:Macaca fascicularis; D008574:Mengovirus / Q000235:genetics*; D051379:Mice; D008807:Mice, Inbred BALB C / Q000276:immunology; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D012367:RNA, Viral / Q000235:genetics / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis / Q000276:immunology; D011995:Recombination, Genetic; D010948:Viral Plaque Assay
D017931:DNA Primers; D015483:HIV Antibodies; D015699:HIV Envelope Protein gp120; D012367:RNA, Viral; D011993:Recombinant Fusion Proteins