Construction and cellular immune response induction of HA-based alphavirus replicon vaccines against human-avian influenza (H5N1)

• Published in: Vaccine 2009-12, Vol.27 (52), p.7451-7458
• Main Authors: Yang, Shi-gui, Wo, Jian-er, Li, Min-wei, Mi, Fen-fang, Yu, Cheng-bo, Lv, Guo-liang, Cao, Hong-Cui, Lu, Hai-feng, Wang, Bao-hong, Zhu, Hanping, Li, Lan-Juan
• Format: Article
• Language: English
• Subjects: Allergy and Immunology; Alphavirus; Alphavirus - immunology; Animals; Antigens; Applied microbiology; Biological and medical sciences; Birds; CD4-Positive T-Lymphocytes - immunology; CD8-Positive T-Lymphocytes - immunology; Cell Line; Cloning; Deoxyribonucleic acid; DNA; Fundamental and applied biological sciences. Psychology; Genes; Hemagglutinin Glycoproteins, Influenza Virus - immunology; Herpes simplex virus 1; Humans; Immune response; Immunity, Cellular; Immunization; Immunogenicity; Influenza A (H5N1) virus; Influenza A Virus, H5N1 Subtype - genetics; Influenza A Virus, H5N1 Subtype - immunology; Influenza in Birds - immunology; Influenza Vaccines - biosynthesis; Influenza Vaccines - immunology; Influenza, Human - immunology; Influenza, Human - prevention & control; Interferon-gamma - immunology; Interleukin-4 - immunology; Mice; Mice, Inbred BALB C; Microbiology; Miscellaneous; Peptides; Phylogenetics; Phylogeny; Plasmids; Proteins; Replicon - immunology; Replicons; Vaccine; Vaccines; Vaccines, antisera, therapeutical immunoglobulins and monoclonal antibodies (general aspects); Viral Structural Proteins - immunology; Virology; VP22
• ISSN: 0264-410X; 1873-2518
• DOI: 10.1016/j.vaccine.2009.05.014

Abstract Several approaches are being taken worldwide to develop vaccines against H5N1 viruses; most of them, however, pose both practical and immunological challenges. One potential strategy for improving the immunogenicity of vaccines involves the use of alphavirus replicons and VP22, a herpes simplex type 1 (HSV-1) protein. In this study, we analysed the antigenic peptides and homogeneity of the HA sequences (human isolates of the H5N1 subtype, from 1997 to 2003) and explored a novel alphavirus replicon system of VP22 fused with HA, to assess whether the immunogenicity of an HA-based replicon vaccine could be induced and augmented via fusion with VP22. Further, replicon particles expressing VP22, and enhanced green fluorescent protein (EGFP) were individually used as controls. Cellular immune responses in mice immunised with replicons were evaluated by identifying specific intracellular cytokine production with flow cytometry (FCM). Animal-based experimentation indicated that both the IL-4 expression of CD4+ T cells and the IFN-γ expression of CD8+ T cells were significantly increased in mice immunised with VPR-HA and VPR-VP22/HA. A dose titration effect vis-à-vis both IL-4 expression and IFN-γ expression were observed in VPR-HA- and VPR-VP22/HA-vaccinated mice. Our results revealed that both VPR-VP22/HA and VPR-HA replicon particles presented a promising approach for developing vaccines against human-avian influenza, and VP22 could enhance the immunogenicity of the HA antigens to which it is fused.