Generation and immunogenicity of novel HIV/AIDS vaccine candidates targeting HIV-1 Env/Gag-Pol-Nef antigens of clade C

被引：73

作者：

Elena Gomez, Carmen

Luis Najera, Jose

Jimenez, Victoria

Bieler, Kurt

Wild, Jens

Kostic, Linda

Heidari, Shirin

Chen, Margaret

Frachette, Marie-Joelle

Pantaleo, Giuseppe

Wolf, Hans

Liljestrom, Peter

Wagner, Ralf

Esteban, Mariano

机构：

[1] CSIC, Ctr Nacl Biotecnol, Dept Mol & Cellular Biol, E-28049 Madrid, Spain

[2] Univ Regensburg, Inst Med Microbiol & Hyg, D-8400 Regensburg, Germany

[3] Karolinska Inst, Dept Microbiol Tumor & Cell Biol, S-17177 Stockholm, Sweden

[4] Sanofi Pasteur, F-69280 Marcy Letoile, France

[5] CHU Vaudois, Dept Med, Lab AIDS Immunopathogenesis, CH-1011 Lausanne, Switzerland

来源：

VACCINE | 2007年 / 25卷 / 11期

关键词：

HIV/AIDS; clade C vaccine; poxvirus vectors; MVA; NYVAC; DNA vectors; SFV vectors; immune response; mouse models;

D O I：

10.1016/j.vaccine.2006.11.051

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

Recombinants based on the attenuated vaccinia virus strains MVA and NYVAC are considered candidate vectors against different human diseases. In this study we have generated and characterized in BALB/c and in transgenic HHD mice the immunogenicity of two attenuated poxvirus vectors expressing in a single locus (TK) the codon optimized HIV-1 genes encoding gp120 and Gag-Pol-Nef (GPN) polyprotein of clade C (referred as MVA-C and NYVAC-Q. In HHD mice primed with either MVA-C or NYVAC-C, or primed with DNA-C and boosted with the poxvirus vectors, the splenic T cell responses against clade C peptides spanning gp120/GPN was broad and mainly directed against Gag-1, Env-1 and Env-2 peptide pools. In BALB/c mice immunized with the homologous or the heterologous combination of poxvirus vectors or with Semliki forest virus (SFV) vectors expressing gp120/GPN, the immune response was also broad but the most immunogenic peptides were Env-1, GPN-1 and GPN-2. Differences in the magnitude of the cellular immune responses were observed between the poxvirus vectors depending on the protocol used. The specific cellular immune response triggered by the poxvirus vectors was Th1 type. The cellular response against the vectors was higher for NYVAC than for MVA in both HHD and BALB/c mice, but differences in viral antigen recognition between the vectors was observed in sera from the poxvirus-immunized animals. These results demonstrate the immunogenic potential of MVA-C and NYVAC-C as novel vaccine candidates against clade C of HIV-1. (c) 2006 Elsevier Ltd. All rights reserved.

引用

页码：1969 / 1992

页数：24

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