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Influenza virus-like particles composed of conserved influenza proteins and GPI-anchored CCL28/GM-CSF fusion proteins enhance protective immunity against homologous and heterologous viruses

文献类型： 外文期刊

作者： Liu, Jing 1 ; Ren, Zhiguang 4 ; Wang, Hongmei 7 ; Zhao, Yongkun 3 ; Wilker, Peter R. 6 ; Yu, Zhijun 8 ; Sun, Weiyang 3 ;

作者机构： 1.CAMS, PUMC, Comparat Med Ctr, Beijing 100021, Peoples R China

2.CAMS, Inst Lab Anim Sci, Beijing 100021, Peoples R China

3.Acad Mil Med Sci, Inst Mil Vet, Key Lab Jilin Prov Zoonosis, Changchun 130122, Jilin, Peoples R China

4.Sch Basic Med, Joint Natl Lab Antibody Drug Engn, Kaifeng 475004, Peoples R China

5.Henan Univ, Kaifeng, Hennan Province, Peoples R China

6.Virginia Commonwealth Univ, Philips Inst Oral Hlth Res, Sch Dent, Richmond, VA 23298 USA

7.Shandong Normal Univ, Coll Life Sci, Key Lab Anim Resistant Biol Shandong, Ruminant Dis Res Ctr, Jinan 250014, Shandong, Peoples R China

8.Shandong Acad Agr Sci, Inst Poultry Sci, Jinan 250023, Shandong, Peoples R China

9.Yangzhou Univ, Jiangsu Coinnovat Ctr Prevent & Control Important, Yangzhou 225009, Jiangsu, Peoples R China

关键词： Influenza cVLPs vaccine; GPI-CCL28; GPI-GM-CSF; Broad-spectrum; Intranasal administration

期刊名称：INTERNATIONAL IMMUNOPHARMACOLOGY （ 影响因子：4.932； 五年影响因子：4.624 ）

ISSN： 1567-5769

年卷期： 2018 年 63 卷

页码：

收录情况： SCI

摘要： Influenza viruses cause significant morbidity and mortality and pose a substantial threat to public health. Vaccination represents the principle means of preventing influenza virus infection. Current vaccine approaches are hindered by the need to routinely reformulate vaccine compositions in an effort to account for the progressive antigenic changes that occur as influenza viruses circulate in the human population. In this study, we evaluated chimeric virus-like particle (cVLP) vaccines containing conserved elements of influenza proteins (HL5M2e (HA stem gene with 5M2e gene inserted) and NP), with or without glycosylphosphatidylinositol-anchored CCL28 (GPI-CCL28) and/or GM-CSF (GPI-GM-CSF) fusion proteins as molecular adjuvants. cVLPs elicited strong humoral and cellular immune responses against homologous and heterologous viruses, and improved survival following lethal challenge with both homologous and heterologous viruses. Inclusion of GPI-anchored adjuvants in cVLP vaccines augmented the generation of influenza-specific humoral and cellular immune responses in mice in comparison to the non-adjuvanted cVLP vaccines. VLPs containing GPI-anchored adjuvants reduced morbidity and improved survival to lethal challenge with homologous and heterologous influenza viruses. This work suggests that VLP vaccines incorporating conserved influenza virus proteins and GPI-anchored molecular adjuvants may serve as a platform for a broadly protective "universal" influenza vaccine.

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