Protective CD8 + T-cell response against Hantaan virus infection induced by immunization with designed linear multi-epit
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RESEARCH
Protective CD8+ T‑cell response against Hantaan virus infection induced by immunization with designed linear multi‑epitope peptides in HLA‑A2.1/Kb transgenic mice Ying Ma1* , Kang Tang1, Yusi Zhang1, Chunmei Zhang1, Linfeng Cheng2, Fanglin Zhang2, Ran Zhuang1, Boquan Jin1 and Yun Zhang1*
Abstract Background: An effective vaccine that prevents disease caused by hantaviruses is a global public health priority, but up to now, no vaccine has been approved for worldwide use. Therefore, novel vaccines with high prophylaxis efficacy are urgently needed. Methods: Herein, we designed and synthesized Hantaan virus (HTNV) linear multi-epitope peptide consisting of HLA-A*02-restricted HTNV cytotoxic T cell (CTL) epitope and pan HLA-DR-binding epitope (PADRE), and evaluated the immunogenicity, as well as effectiveness, of multi-epitope peptides in HLA-A2.1/Kb transgenic mice with interferon (IFN)-γ enzyme-linked immunospot assay, cytotoxic mediator detection, proliferation assay and HTNV-challenge test. Results: The results showed that a much higher frequency of specific IFN-γ-secreting CTLs, high levels of granzyme B production, and a strong proliferation capacity of specific CTLs were observed in splenocytes of mice immunized with multi-epitope peptide than in those of a single CTL epitope. Moreover, pre-immunization of multi-epitope peptide could reduce the levels of HTNV RNA loads in the liver, spleen and kidneys of mice, indicating that specific CTL responses induced by multi-epitope peptide could reduce HTNV RNA loads in vivo. Conclusions: This study may provide an important foundation for the development of novel peptide vaccines for HTNV prophylaxis. Keywords: Hantaan virus, Multi-epitope peptide, Cytotoxic T cell response, Vaccine, HLA-A2.1/Kb transgenic mice Background Rodent-borne orthohantaviruses of the family Hantaviridae are widespread zoonotic pathogens that cause two diseases in humans, hemorrhagic fever with renal syndrome (HFRS) and hantavirus cardiopulmonary *Correspondence: [email protected]; [email protected] 1 Department of Immunology, The Fourth Military Medical University, 169 Changle West Road, Xi’an 710032, China Full list of author information is available at the end of the article
syndrome (HCPS) [1, 2]. At present, over 28 hantaviruses have been identified. The Old World hantaviruses, such as the prototypic member Hantaan virus (HTNV), Puumala virus (PUUV) and Dobrava virus (DOBV), are etiological agents in Asia and Europe, and together with the worldwide distributed Seoul virus (SEOV), they cause the majority of cases of HFRS [3, 4]. While New World hantaviruses, including the Andes virus (ANDV) and Sin Nombre virus (SNV), were found predominantly in the Americas—causing HCPS with a fatality rate of up to 40%
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