Protein transfer-mediated surface engineering to adjuvantate virus-like nanoparticles for enhanced anti-viral immune responses.
Recombinant virus-like nanoparticles (VLPs) are a promising nanoparticle platform to develop safe vaccines for many viruses. Herein, we describe a novel and rapid protein transfer process to enhance the potency of enveloped VLPs by decorating influenza VLPs with exogenously added glycosylphosphatidylinositol-anchored immunostimulatory molecules (GPI-ISMs). With protein transfer, the level of GPI-ISM incorporation onto VLPs is controllable by varying incubation time and concentration of GPI-ISMs added. ISM incorporation was dependent upon the presence of a GPI-anchor and incorporated proteins were stable and functional for at least 4weeks when stored at 4°C. Vaccinating mice with GPI-granulocyte macrophage colony-stimulating factor (GM-CSF)-incorporated-VLPs induced stronger antibody responses and better protection against a heterologous influenza virus challenge than unmodified VLPs. Thus, VLPs can be enriched with ISMs by protein transfer to increase the potency and breadth of the immune response, which has implications in developing effective nanoparticle-based vaccines against a broad spectrum of enveloped viruses.


BACKGROUND
The inherent problem with current influenza vaccines is that they do not generate effective cross-protection against heterologous viral strains. In this article, the authors described the development of virus-like nanoparticles (VLPs) as influenza vaccines with enhanced efficacy for cross-protection, due to an easy protein transfer modification process.
Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA, USA.
Jaina M
JM
Patel
Center for Inflammation, Immunity and Infection, Institute for Biomedical Sciences, Georgia State University, Atlanta, GA, USA; Animal and Plant Quarantine Agency, Anyang City, Gyeonggi-do, Korea.
Min-Chul
MC
Kim
Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA, USA.
Vincent F
VF
Vartabedian
Center for Inflammation, Immunity and Infection, Institute for Biomedical Sciences, Georgia State University, Atlanta, GA, USA.
Yu-Na
YN
Lee
Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA, USA.
Sara
S
He
Department of Global Medical Science, Sungshin Women's University, Seoul, Korea.
Jae-Min
JM
Song
Department of Chemical and Materials Engineering, University of Alberta, Edmonton, AB, Canada.
Hyo-Jick
HJ
Choi
Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA, USA.
Satoshi
S
Yamanaka
Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA, USA.
Nikhil
N
Amaram
Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA, USA.
Anna
A
Lukacher
Department of Chemical and Materials Engineering, University of Alberta, Edmonton, AB, Canada.
Carlo D
CD
Montemagno
Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA, USA.
Richard W
RW
Compans
Center for Inflammation, Immunity and Infection, Institute for Biomedical Sciences, Georgia State University, Atlanta, GA, USA.
Sang-Moo
SM
Kang
Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA, USA. Electronic address: pselvar@emory.edu.
Periasamy
P
Selvaraj
D000276:Adjuvants, Immunologic / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D000914:Antibodies, Viral / Q000276:immunology; D016466:CHO Cells; D003412:Cricetulus; D005260:Female; D017261:Glycosylphosphatidylinositols / Q000737:chemistry / Q000276:immunology*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000737:chemistry / Q000276:immunology*; D006801:Humans; D007111:Immunity, Cellular; D056724:Immunity, Humoral; D007252:Influenza Vaccines / Q000737:chemistry / Q000276:immunology*; D008807:Mice, Inbred BALB C; D053758:Nanoparticles / Q000737:chemistry; D009975:Orthomyxoviridae / Q000737:chemistry / Q000276:immunology*; D009976:Orthomyxoviridae Infections / Q000276:immunology / Q000517:prevention & control*; D014611:Vaccination; D014771:Virion / Q000737:chemistry / Q000276:immunology*
D000276:Adjuvants, Immunologic; D000914:Antibodies, Viral; D017261:Glycosylphosphatidylinositols; D007252:Influenza Vaccines; D016178:Granulocyte-Macrophage Colony-Stimulating Factor
GM-CSF; GPI-anchored proteins; Influenza; Protein transfer; Virus-like particles