A mRNA Vaccine for Crimean–Congo Hemorrhagic Fever Virus Expressing Non-Fusion GnGc Using NSm Linker Elicits Unexpected Immune Responses in Mice
Tong Chen,
Zhe Ding,
Xuejie Li,
Yingwen Li,
Jiaming Lan,
Gary Wong
Affiliations
Tong Chen
Viral Hemorrhagic Fever Research Unit, Chinese Academy of Sciences (CAS) Key Laboratory of Molecular Virology & Immunology, Shanghai Institute of Immunity and Infection (Formerly Institut Pasteur of Shanghai), Chinese Academy of Sciences, Shanghai 200031, China
Zhe Ding
Viral Hemorrhagic Fever Research Unit, Chinese Academy of Sciences (CAS) Key Laboratory of Molecular Virology & Immunology, Shanghai Institute of Immunity and Infection (Formerly Institut Pasteur of Shanghai), Chinese Academy of Sciences, Shanghai 200031, China
Xuejie Li
Viral Hemorrhagic Fever Research Unit, Chinese Academy of Sciences (CAS) Key Laboratory of Molecular Virology & Immunology, Shanghai Institute of Immunity and Infection (Formerly Institut Pasteur of Shanghai), Chinese Academy of Sciences, Shanghai 200031, China
Yingwen Li
Viral Hemorrhagic Fever Research Unit, Chinese Academy of Sciences (CAS) Key Laboratory of Molecular Virology & Immunology, Shanghai Institute of Immunity and Infection (Formerly Institut Pasteur of Shanghai), Chinese Academy of Sciences, Shanghai 200031, China
Jiaming Lan
Viral Hemorrhagic Fever Research Unit, Chinese Academy of Sciences (CAS) Key Laboratory of Molecular Virology & Immunology, Shanghai Institute of Immunity and Infection (Formerly Institut Pasteur of Shanghai), Chinese Academy of Sciences, Shanghai 200031, China
Gary Wong
Viral Hemorrhagic Fever Research Unit, Chinese Academy of Sciences (CAS) Key Laboratory of Molecular Virology & Immunology, Shanghai Institute of Immunity and Infection (Formerly Institut Pasteur of Shanghai), Chinese Academy of Sciences, Shanghai 200031, China
Crimean–Congo hemorrhagic fever (CCHF), caused by Crimean–Congo Hemorrhagic virus (CCHFV), is listed in the World Health Organization’s list of priority diseases. The high fatality rate in humans, the widespread distribution of CCHFV, and the lack of approved specific vaccines are the primary concerns regarding this disease. We used microfluidic technology to optimize the mRNA vaccine delivery system and demonstrated that vaccination with nucleoside-modified CCHFV mRNA vaccines encoding GnNSmGc (vLMs), Gn (vLMn), or Gc (vLMc) induced different immune responses. We found that both T-cell and B-cell immune responses induced by vLMc were better than those induced by vLMn. Interestingly, immune responses were found to be lower for vLMs, which employed NSm to link Gn and Gc for non-fusion expression, compared to those for vLMc. In conclusion, our results indicated that NSm could be a factor that leads to decreased specific immune responses in the host and should be avoided in the development of CCHFV vaccine antigens.
