Induction of Hantaan virus-specific immune responses in C57BL/6 mice by immunization with a modified recombinant adenovirus containing the chimeric gene, GcS0.7

Abstract

Hantavirus glycoprotein Gc is one of the main components that contribute to the generation of humoral immune responses, while the nucleocapsid protein (NP) is involved in cellular immune responses through the induction of antibody-dependent cytotoxic T cells. In this study, a chimeric gene, GcS0.7, which encodes a fusion protein containing Gc and truncated NP, was constructed as a candidate for Hantaan virus (HTNV) vaccine development. The chimeric gene was cloned into an adenoviral vector in conjunction with the powerful hybrid cytomegalovirus (CMV) enhancer/chicken β-actin (CAG) promoter or the woodchuck hepatitis virus (WHV) post-transcriptional regulatory element (WPRE), or both. Both elements increased the expression level of the fusion protein. The rAd-GcS0.7-pCAG group demonstrated the highest fusion protein expression level, with a 2.3-fold increase compared with the unmodified adenoviral vector. To further evaluate the humoral and cellular immunity induced by the recombinant adenovirus, the antibody titers, interferon (IFN)-γ secretion level and cytotoxic T cell ratio were detected in immunized mice. The strongest HTNV‑specific humoral and cellular immune responses were detected in the rAd-GcS0.7‑pCAG group. The immunogenicity of these recombinant adenoviruses was compared with that of the inactivated vaccine through a series of immunological assays. In terms of the cellular immune responses, the rAd-GcS0.7-pCAG group even exceeded those induced by the vaccine control. The CAG hybrid promoter improved not only the expression level, but also the immunogenicity of the fusion protein, and may thus provide a promising strategy for HTNV vaccine research.

Animal Models for the Study of Rodent-Borne Hemorrhagic Fever Viruses: Arenaviruses and Hantaviruses

“…BALB/c mice [ 196 , 218 – 236 ] have been the predominant model to study hantavirus vaccines but others including C57BL/6 [ 215 , 227 , 229 , 237 – 246 ] and NMRI [ 247 ] mice have also been employed to demonstrate vaccine efficacy against HTNV [ 215 , 218 , 219 , 223 , 225 ], PUUV [ 221 , 222 , 232 , 236 , 247 ], SEOV [ 196 , 232 ], DOBV [ 227 , 248 ], ANDV [ 235 ], and SNV [ 220 , 232 , 249 , 250 ]. Inactivated HTNV virus, one of the earliest hantavirus vaccines, was initially tested in the murine model and was found to produce protective cellular and humoral responses, including neutralizing antibody protection [ 218 , 219 , 223 , 240 , 241 , 244 – 246 ]. Subsequently subunit DNA vaccines and virus vector vaccines, including vaccinia virus, lentivirus, adenovirus among others, targeting nucleocapsid, and glycoproteins were also tested in murine models and found to induce broad seroconversion, including robust neutralizing antibody titers and a mixture of T h 1 and T h 2 T cell responses capable of protecting mice from hantavirus infection [ 196 , 215 , 220 – 222 , 229 , 230 , 235 , 246 , 249 , 251 ].…”

A recombinant pseudotyped lentivirus expressing the envelope glycoprotein of Hantaan virus induced protective immunity in mice

“…Furthermore, our ELISA-based neutralization test is more convenient in operation and more stable in results [ 41 ]. It was also used in other experiments in our laboratory reported before [ 40 , 42 ].…”

Adenovirus-based vaccines—a platform for pandemic preparedness against emerging viral pathogens

“…Lethality ranges from 0.1%-15% for HFRS and up to 40%-50% for HPS (Table 1). 138,139 No licensed vaccine currently exists. The long incubation period, along with reports of human-to-human transmission during outbreaks of ANDV, are of increasing concern.…”