Chimeras between the human immunodeficiency virus (HIV-1) Env and vaccinia virus immunogenic proteins p14 and p39 generate in mice broadly reactive antibodies and specific activation of CD8+ T cell responses to Env
Identifieur interne : 003665 ( Main/Exploration ); précédent : 003664; suivant : 003666Chimeras between the human immunodeficiency virus (HIV-1) Env and vaccinia virus immunogenic proteins p14 and p39 generate in mice broadly reactive antibodies and specific activation of CD8+ T cell responses to Env
Auteurs : Manuel Collado [Espagne] ; Dolores Rodr Guez [Espagne] ; Juan Ram N Rodr Guez [Espagne] ; Isabel Vázquez [Espagne] ; Rosa M. Gonzalo [Espagne] ; Mariano Esteban [Espagne]Source :
- Vaccine [ 0264-410X ] ; 2000.
English descriptors
- Teeft :
- Aids research, Amino acids, Animals immunised, Assay, Cell cultures, Cell extracts, Cell response, Cell responses, Chimera, Chimeric, Chimeric proteins, Collado, Elisa, Elispot assay, Envelope glycoprotein, Epitope, Esteban, Fusion protein, Fusion proteins, Glycosylation, Human virus, Human virus type, Humoral, Immune, Immune response, Immune system, Immunisation, Immunised, Immunised animals, Immunodominant, Immunogenic, Immunogenic proteins, Infectious diseases, Mice immunised, Monoclonal antibodies, Mung bean, National academy, Neutralisation, Neutralising, Neutralizing, Peptide, Plasmid, Protective immunity, Protein, Reactive, Reactive antibodies, Recombinant, Recombinant virus, Recombinant viruses, Rodriguez, Secreting cells, Strain iiib, Vaccine, Vaccinia, Vaccinia virus, Virology, Western blot.
Abstract
Abstract: A vaccine based on the envelope protein (Env) of the human immunodeficiency virus type 1 (HIV-1) that triggers widely reactive antibodies might be a desirable approach to control virus infection. To expose epitopes which could induce broadly reactive antibodies against HIV-1 Env, we have generated vaccinia virus (VV) recombinants that express Env fused at its N- or C-terminus with two major antigenic proteins of VV, p14 (A27L gene) and p39 (A4L gene). Biochemical analysis of the chimeric proteins in cell cultures revealed that, in all cases, recombinant viruses expressed the correct fusion proteins. When p14 or p39 are fused at the N-terminus of Env the chimeric proteins are poorly glycosylated but when p14 or p39 are fused at the C-terminus of Env, the chimeric proteins are fully glycosylated. In Balb/c mice, immunisation with the referred VV recombinants induced similar levels of CD8+ T cell specific responses to Env as immunisation with the entire Env protein. The humoral immune response triggered by the fusion proteins was broader than in animals immunised with VV expressing the entire Env (VVEnv1), and was directed to epitopes outside of the V3 loop (V1/V2, C1, C2, C4). One of the chimeric constructs induced a better neutralising antibody response than VVEnv1. We conclude that fusing VV proteins p14 or p39 to Env provides an effective means to induce broadly reactive antibodies and CD8+ T cell responses to Env. This approach might have utility against HIV and other pathogens.
Url:
DOI: 10.1016/S0264-410X(00)00112-2
Affiliations:
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To expose epitopes which could induce broadly reactive antibodies against HIV-1 Env, we have generated vaccinia virus (VV) recombinants that express Env fused at its N- or C-terminus with two major antigenic proteins of VV, p14 (A27L gene) and p39 (A4L gene). Biochemical analysis of the chimeric proteins in cell cultures revealed that, in all cases, recombinant viruses expressed the correct fusion proteins. When p14 or p39 are fused at the N-terminus of Env the chimeric proteins are poorly glycosylated but when p14 or p39 are fused at the C-terminus of Env, the chimeric proteins are fully glycosylated. In Balb/c mice, immunisation with the referred VV recombinants induced similar levels of CD8+ T cell specific responses to Env as immunisation with the entire Env protein. The humoral immune response triggered by the fusion proteins was broader than in animals immunised with VV expressing the entire Env (VVEnv1), and was directed to epitopes outside of the V3 loop (V1/V2, C1, C2, C4). One of the chimeric constructs induced a better neutralising antibody response than VVEnv1. We conclude that fusing VV proteins p14 or p39 to Env provides an effective means to induce broadly reactive antibodies and CD8+ T cell responses to Env. This approach might have utility against HIV and other pathogens.</div></front></TEI><affiliations><list><country><li>Espagne</li></country><region><li>Communauté de Madrid</li></region></list><tree><country name="Espagne"><region name="Communauté de Madrid"><name sortKey="Collado, Manuel" sort="Collado, Manuel" uniqKey="Collado M" first="Manuel" last="Collado">Manuel Collado</name></region><name sortKey="Esteban, Mariano" sort="Esteban, Mariano" uniqKey="Esteban M" first="Mariano" last="Esteban">Mariano Esteban</name><name sortKey="Esteban, Mariano" sort="Esteban, Mariano" uniqKey="Esteban M" first="Mariano" last="Esteban">Mariano Esteban</name><name sortKey="Gonzalo, Rosa M" sort="Gonzalo, Rosa M" uniqKey="Gonzalo R" first="Rosa M." last="Gonzalo">Rosa M. Gonzalo</name><name sortKey="Rodr Guez, Dolores" sort="Rodr Guez, Dolores" uniqKey="Rodr Guez D" first="Dolores" last="Rodr Guez">Dolores Rodr Guez</name><name sortKey="Rodr Guez, Juan Ram N" sort="Rodr Guez, Juan Ram N" uniqKey="Rodr Guez J" first="Juan Ram N" last="Rodr Guez">Juan Ram N Rodr Guez</name><name sortKey="Vazquez, Isabel" sort="Vazquez, Isabel" uniqKey="Vazquez I" first="Isabel" last="Vázquez">Isabel Vázquez</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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