Fusion with extracellular domain of cytotoxic T-lymphocyte-associated-antigen 4 leads to enhancement of immunogenicity of Hantaan virus DNA vaccines in C57BL/6 mice

DNA plasmids encoding the HTNV nucleocapsid protein (N) and glycoprotein (Gn and Gc) in fusion to the extracellular domain of cytotoxic T-lymphocyte-associated-antigen 4 (eCTLA-4) targeting to antigen presenting cells (APCs) were constructed. Intramuscular immunization of mice with plasmids expressing eCTLA-4-HTNV-N/GP fusion proteins leads to a significant enhancement of the specific antibody response as well as cytotoxic T-lymphocyte (CTL) response in C57BL/6 mice. Moreover, this effect could be further augmented when co-administered with CpG motifs.Modification of viral antigen in fusion to bioactive factor will be promising to confer efficient antigen presentation and improve the potency of DNA vaccine in mice.Hantaan virus (HTNV) (Bunyaviridae family, Hantavirus genus) is the causative agent of the most severe form of a rodent-borne disease known as hemorrhagic fever with renal syndrome (HFRS). Other hantaviruses that are known to cause HFRS include Seoul virus (SEOV), Dobrava virus (DOBV) and Puumala virus (PUUV), which cause disease in Asia, Europe, Scandinavia, and western Russia respectively [1]. In addition, a few hantaviruses have been identified to associate with outbreaks of a highly lethal disease, hantavirus pulmonary syndrome (HPS), in the Americas [2]. Since hantaviruses can cause epidemics with high morbidity, and currently there is no proven therapy for hantaviral disease, a safe and effective vaccine(s) against hantaviruses infection is necessary. HTNV causes the most severe form of HFRS and around 150,000 cases of HFRS are reported worldwide annually, with the majority of HFRS occurring in Asia [3].Hantaviruses are enveloped, negative strands RNA viruses consisting of three single RNA segments designated S (small), M (medium), and L (large), which encode the nucleocapsid (N) protein, envelope glycoproteins (Gn and Gc), and the RNA polymerase respectively [4]. As a key surface antigen, glycoproteins (Gn and Gc) bear the epitopes which could elici