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Int Immunopharmacol. 2018 Oct;63:119-128. doi: 10.1016/j.intimp.2018.07.011. Epub 2018 Aug 3.

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.

Author information

1
Comparative Medicine Center, Peking Union Medical College (PUMC) and Institute of Laboratory Animal Sciences, Chinese Academy of Medical Sciences (CAMS), Beijing 100021, China; Key Laboratory of Jilin Province for Zoonosis, Institute of Military Veterinary, Academy of Military Medical Sciences, Changchun, Jilin Province 130122, China.
2
Joint National Laboratory for Antibody Drug Engineering, School of Basic Medicine, Kaifeng 475004, China; Henan University, Kaifeng, Hennan Province, China.
3
Key Laboratory of Animal Resistant Biology of Shandong, Ruminant Disease Research Center, College of Life Science, Shandong Normal University, Shandong Province 250014, China.
4
Key Laboratory of Jilin Province for Zoonosis, Institute of Military Veterinary, Academy of Military Medical Sciences, Changchun, Jilin Province 130122, China.
5
Philips Institute for Oral Health Research, School of Dentistry, Virginia Commonwealth University, Richmond, Virginia 23298, USA.
6
Institute of Poultry Science, Shandong Academy of Agricultural Sciences, Jinan 250023, China.
7
Key Laboratory of Jilin Province for Zoonosis, Institute of Military Veterinary, Academy of Military Medical Sciences, Changchun, Jilin Province 130122, China; Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou University, Yangzhou 225009, China.
8
Comparative Medicine Center, Peking Union Medical College (PUMC) and Institute of Laboratory Animal Sciences, Chinese Academy of Medical Sciences (CAMS), Beijing 100021, China.
9
Key Laboratory of Jilin Province for Zoonosis, Institute of Military Veterinary, Academy of Military Medical Sciences, Changchun, Jilin Province 130122, China; Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou University, Yangzhou 225009, China. Electronic address: gaoyuwei@gmail.com.
10
Comparative Medicine Center, Peking Union Medical College (PUMC) and Institute of Laboratory Animal Sciences, Chinese Academy of Medical Sciences (CAMS), Beijing 100021, China; Key Laboratory of Jilin Province for Zoonosis, Institute of Military Veterinary, Academy of Military Medical Sciences, Changchun, Jilin Province 130122, China; Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou University, Yangzhou 225009, China. Electronic address: xiaxzh@cae.cn.

Abstract

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.

KEYWORDS:

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

PMID:
30081250
DOI:
10.1016/j.intimp.2018.07.011
[Indexed for MEDLINE]

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