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.
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.
Collado
M
M
Department of Molecular and Cellular Biology, Centro Nacional de Biotecnología, CSIC, Campus Universidad Autonoma, E-28049, Madrid, Spain.
Rodríguez
D
D
Rodríguez
J R
JR
Vázquez
I
I
Gonzalo
R M
RM
Esteban
M
M
D016915:AIDS Vaccines / Q000276:immunology*; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002522:Chlorocebus aethiops; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D015686:Gene Products, env / Q000276:immunology*; D006031:Glycosylation; D015483:HIV Antibodies / Q000096:biosynthesis*; D015497:HIV-1 / Q000276:immunology*; D006367:HeLa Cells; D006801:Humans; D007114:Immunization; D051379:Mice; D008807:Mice, Inbred BALB C; D011993:Recombinant Fusion Proteins / Q000276:immunology*; D014614:Vaccines, Synthetic / Q000276:immunology*; D014616:Vaccinia virus / Q000276:immunology*; D014764:Viral Proteins / Q000276:immunology*
D016915:AIDS Vaccines; D015686:Gene Products, env; D015483:HIV Antibodies; D011993:Recombinant Fusion Proteins; D014614:Vaccines, Synthetic; D014764:Viral Proteins