Methanobrevibacter smithii archaeosomes-entrapped mzNL4-3 virus-like particles induce specific T helper 1-oriented cellular and humoral responses against HIV-1.

Despite numerous and tremendous achievements in the development and standardization of HIV vaccines, there are still lots of vague concepts in HIV vaccinology. Various approaches have been applied to design an efficient HIV vaccine. Due to their lack of replication ability and expression of native antigens at the same time virus-like particles, such as previously introduced mzNL4-3 HIV-1 VLPs are among the highlighted candidates in this field. On the other part, application of adjuvants is an inseparable strategy in the vaccine development researches. Archaeosomes are liposomal adjuvants with intensifiying features of T helper 1 and cytotoxic T-cells responses. Archaeosomes derived from Methanobrevibacter smithii has been shown to enhance MHC class I-dependent antigen presentation and hence, are to be advantageous in the development of vaccines against viral infections. Herein, we have studied efficiency of mzNL4-3 VLPs entrapped in M. smithii archaeosomes as an HIV-1 vaccine candidate to induce humoral and cellular responses in BALB/c mice. Analysis of total and subtype-specific anti-Env IgG antibody, as well as, cytokine secretion pattern revealed an efficient promotion of anti-HIV specific T helper 1 responses in immunized animals. This finding was evidenced by the significant dominance of IgG2a subtype in the sera and considerable secretion of IFN-γ by specifically induced splenocytes of mice immunized with VLP-containing archaeosomes (VLP+ Archaeosome). In addition, ELISpot assay verified these results and indicated the significantly higher frequency of IFN-γ secreting splenocytes in immunized models. The ratio of IFN-γ to IL-4 spot forming cells (SFCs) in the VLP+ Archaeosome immunized mice was also higher than that of the other groups immunized with either VLP-free archaeosomes or VLPs formulated with complete/incomplete Freund's adjuvants. These results propound M. smithii archaeosomes-entrapped mzNL4-3 VLPs as a promising immunogen which specifically induces and augments T-helper 1 oriented responses against HIV antigens.