Immunogenicity of virus-like Semliki Forest virus replicon particles expressing Indian HIV-1C gag, env and polRT genes

被引:11
作者
Ajbani, Seema P. [1 ,2 ]
Velhal, Shilpa M. [1 ]
Kadam, Ravindra B. [1 ]
Patel, Vainav V. [1 ]
Lundstrom, Kenneth [3 ]
Bandivdekar, Atmaram H. [1 ]
机构
[1] Natl Inst Res Reprod Hlth, Dept Biochem & Virol, JM St, Mumbai 400012, Maharashtra, India
[2] Univ Mumbai, Dept Zool, Smt CHM Coll, Ulhasnagar 421003, Maharashtra, India
[3] PanTherapeutics, Lutry, Switzerland
关键词
Semliki Forest virus; HIV-1 subtype C (HIV-1C); Virus-like Replicon Particle; T cell response; Humoral response; T-CELL RESPONSES; HUMORAL IMMUNE-RESPONSES; LOUPING-ILL VIRUS; SUBTYPE-C VACCINE; VIRAL LOAD; CYNOMOLGUS MONKEYS; DENDRITIC CELLS; EFFICACY TRIAL; BOOST REGIMEN; DOUBLE-BLIND;
D O I
10.1016/j.imlet.2017.08.019
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Development of a vaccine targeting human immunodeficiency virus-1 subtype C (HIV-1C) is an important public health priority in regions with a high prevalence of the Glade C virus. The present study demonstrates the immunogenicity of recombinant Semliki Forest virus (SFV)-based virus-like replicon particles (VRPs) expressing Indian HIV-1C env/gag/polRT genes. Immunization of mice with recombinant VRPs in a homologous prime-boost protocol, either individually or in combination, elicited significant antigen-specific IFN-gamma T cell responses as detected by the ELISPOT assay. Additionally, Gag-specific TNF-alpha secreting CD8(+) and CD4(+) T cells and Env-specific IL-2 secreting T cells were also elicited by mice immunized with Gag and Env constructs, respectively, as estimated by intracellular cytokine staining assay. Moreover, an HIV Pol-specific TNF-alpha response was elicited in mice immunized with a combination of the three VRP constructs. Furthermore, HIV-1C Gag and Env-specific binding antibodies were elicited as verified by gp120 ELISA and p24 Gag ELISA, respectively. The immunogenicity of VRPs was found to be higher as compared to that of RNA replicons and VRPs may therefore be promising preventive and therapeutic candidate vaccines for the control and management of HIV/AIDS.
引用
收藏
页码:221 / 232
页数:12
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