title: M2e-immobilized gold nanoparticles as influenza A vaccine: Role of soluble M2e and longevity of protection.
abstract: Influenza virus causes seasonal epidemics and also poses a high risk for pandemics. To develop a broadly cross-protective influenza vaccine we have previously shown that a formulation consisting of the extracellular domain of M2 membrane protein (M2e) immobilized on gold nanoparticles (AuNPs) and soluble CpG as an adjuvant can elicit protective immunity against different influenza A subtypes. The vaccine formulation contains M2e that is immobilized on AuNPs, and an excess amount that is freely dissolved in solution, whose role in inducing protective immunity against virus infection is unclear. Using a mouse model, the current study shows that inclusion of excess soluble M2e antigen along with M2e immobilized on AuNPs is vital for inducing high levels of antibody response, and in providing complete protection against lethal influenza virus challenge. We also show that the vaccine induces long-lasting protection against mortality and morbidity upon lethal challenge with influenza A virus.
authors.affiliation: Department of Chemical Engineering, Texas Tech University, Lubbock, TX 79409, USA.
authors.forename: Wenqian
authors.initials: W
authors.lastname: Tao
authors.affiliation: Department of Chemical Engineering, Texas Tech University, Lubbock, TX 79409, USA. Electronic address: harvinder.gill@ttu.edu.
authors.forename: Harvinder S
authors.initials: HS
authors.lastname: Gill
mesh_terms: D000276:Adjuvants, Immunologic; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood*; D004195:Disease Models, Animal; D005260:Female; D006046:Gold; D055767:Immobilized Proteins; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology*; D007252:Influenza Vaccines / Q000008:administration & dosage / Q000276:immunology*; D053768:Metal Nanoparticles; D008807:Mice, Inbred BALB C; D009838:Oligodeoxyribonucleotides / Q000276:immunology; D009976:Orthomyxoviridae Infections / Q000517:prevention & control*; D064166:Vaccine Potency; D014763:Viral Matrix Proteins / Q000276:immunology*; D000086082:Viroporin Proteins
chemical_list: D000276:Adjuvants, Immunologic; D000914:Antibodies, Viral; D006046:Gold; D055767:Immobilized Proteins; D007252:Influenza Vaccines; D009838:Oligodeoxyribonucleotides; D014763:Viral Matrix Proteins; C408982:CPG-oligonucleotide; C488937:M2 protein, Influenza A virus; D000086082:Viroporin Proteins
keywords: Influenza; Long-term protection; Nanoparticle-conjugated M2e; Soluble M2e; Universal vaccine
references.citation: PLoS One. 2011;6(3):e17642
references.pmid: 21408610
references.citation: PLoS One. 2013;8(3):e59081
references.pmid: 23527091
references.citation: Blood. 2004 Apr 15;103(8):3058-64
references.pmid: 15070685
references.citation: Vaccine. 2004 Aug 13;22(23-24):2993-3003
references.pmid: 15297047
references.citation: Curr Opin Virol. 2013 Jun;3(3):357-62
references.pmid: 23731601
references.citation: J Am Chem Soc. 2004 Aug 18;126(32):10076-84
references.pmid: 15303884
references.citation: N Engl J Med. 2005 Sep 29;353(13):1374-85
references.pmid: 16192482
references.citation: Methods Mol Biol. 2005;303:85-99
references.pmid: 15923677
references.citation: Immunity. 2006 Jan;24(1):5-9
references.pmid: 16413916
references.citation: Colloids Surf B Biointerfaces. 2008 Oct 15;66(2):274-80
references.pmid: 18722754
references.citation: J Phys Chem B. 2006 Aug 17;110(32):15700-7
references.pmid: 16898714
references.citation: Biochem Biophys Res Commun. 2010 Mar 19;393(4):649-55
references.pmid: 20153731
references.citation: Virology. 1991 Jul;183(1):32-43
references.pmid: 2053285
references.citation: Vaccine. 2014 Jan 9;32(3):327-37
references.pmid: 24295808
references.citation: Scand J Immunol. 2004 Jan;59(1):1-15
references.pmid: 14723616
references.citation: Vaccine. 2003 May 1;21(16):1776-9
references.pmid: 12686093
references.citation: J Colloid Interface Sci. 2014 Jul 15;426:31-8
references.pmid: 24863761
references.citation: J Virol. 2002 Nov;76(21):10717-23
references.pmid: 12368314
references.citation: Nanoscale Res Lett. 2009 May 8;4(8):858-864
references.pmid: 20596373
references.citation: Pediatr Nurs. 2006 Jan-Feb;32(1):76-81
references.pmid: 16572544
references.citation: Vaccine. 2006 Nov 10;24(44-46):6597-601
references.pmid: 16814430
references.citation: Cell. 1985 Mar;40(3):627-33
references.pmid: 3882238
references.citation: Vaccine. 2014 Jun 17;32(29):3664-9
references.pmid: 24793947
references.citation: Emerg Infect Dis. 2006 Jan;12(1):9-14
references.pmid: 16494710
references.citation: Influenza Other Respir Viruses. 2011 May;5(3):157-66
references.pmid: 21477134
references.citation: Toxicol Appl Pharmacol. 2009 Apr 1;236(1):16-24
references.pmid: 19162059
references.citation: PLoS One. 2014;9(4):e94051
references.pmid: 24714362
references.citation: Emerg Infect Dis. 2007 Mar;13(3):426-35
references.pmid: 17552096
references.citation: Nucleic Acids Res. 2002 Apr 1;30(7):1558-62
references.pmid: 11917016
references.citation: Nano Life. 2014 Jun 1;4(2):1450004
references.pmid: 25825595
references.citation: PLoS One. 2015;10(3):e0117203
references.pmid: 25756283
references.citation: Sci Rep. 2014;4:3775
references.pmid: 24441019
references.citation: J Phys Chem A. 2007 Dec 13;111(49):12229-37
references.pmid: 17914772
references.citation: Acc Chem Res. 2008 Dec;41(12):1721-30
references.pmid: 18712884
references.citation: Mol Ther. 2013 Feb;21(2):485-92
references.pmid: 23247101
references.citation: Nat Med. 1999 Oct;5(10):1157-63
references.pmid: 10502819
references.citation: Chem Soc Rev. 2011 Mar;40(3):1647-71
references.pmid: 21082078
references.citation: Vaccine. 2008 Jan 10;26(2):201-14
references.pmid: 18063235
references.citation: Vaccine. 2009 Feb 25;27(9):1440-7
references.pmid: 19146898