Increased T cell breadth and antibody response elicited in prime-boost regimen by viral vector encoded homologous SIV Gag/Env in outbred CD1 mice

Journal of Translational Medicine

Research

Anne-Marie Carola Andersson¹  Peter Johannes Holst¹ 

[1] Department of Immunology and Microbiology, Center for Medical Parasitology, University of Copenhagen, Copenhagen, Denmark;

关键词: Adenoviral vectors;    Human immunodeficiency virus;    Vaccine;    Virus-like particles;   

DOI  :  10.1186/s12967-016-1102-7

 received in 2016-10-12, accepted in 2016-11-30,  发布年份 2016

来源: Springer

【 摘 要 】

BackgroundA major obstacle for the development of HIV vaccines is the virus’ worldwide sequence diversity. Nevertheless, the presence of T cell epitopes within conserved regions of the virus’ structural Gag protein and conserved structures in the envelope (env) sequence raises the possibility that cross-reactive responses may be induced by vaccination. In this study, the aim was to investigate the importance of antigenic match on immunodominance and breadth of obtainable T cell responses.MethodsOutbred CD1 mice were immunized with either heterologous (SIVmac239 and HIV-1 clade B consensus) or homologous (SIVmac239) gag sequences using adenovirus (Ad5) and MVA vectors. Env (SIVmac239) was co-encoded in the vectors to study the induction of antibodies, which is a primary target of current HIV vaccine designs. All three vaccines were designed as virus-encoded virus-like particle vaccines. Antibody responses were analysed by ELISA, avidity ELISA, and neutralization assay. T cell responses were determined by intracellular cytokine staining of splenocytes.ResultsThe homologous Env/Gag prime-boost regimen induced higher Env binding antibodies, and induced stronger and broader Gag specific CD8+ T cell responses than the homologous Env/heterologous Gag prime-boost regimen. Homologous Env/heterologous Gag immunization resulted in selective boosting of Env specific CD8+ T cell responses and consequently a paradoxical decreased recognition of variant sequences including conserved elements of p24 Gag.ConclusionsThese results contrast with related studies using Env or Gag as the sole antigen and suggest that prime-boost immunizations based on homologous SIVmac239 Gag inserts is an efficient component of genetic VLP vaccines—both for induction of potent antibody responses and cross-reactive CD8+ T cell responses.

【 授权许可】

CC BY   
© The Author(s) 2016