Consensus M2e peptide conjugated to gold nanoparticles confers protection against H1N1, H3N2 and H5N1 influenza A viruses.
The extracellular domain of influenza A ion channel membrane matrix protein 2 (M2e) is considered to be a potential candidate to develop a universal influenza A vaccine. However poor immunogenicity of M2e presents a significant roadblock. We have developed a vaccine formulation comprising of the consensus M2e peptide conjugated to gold nanoparticles (AuNPs) with CpG as a soluble adjuvant (AuNP-M2e + sCpG). We demonstrate that intranasal delivery of AuNP-M2e + sCpG in mice induces lung B cell activation and robust serum anti-M2e immunoglobulin G (IgG) response, with stimulation of both IgG1 and IgG2a subtypes. Using Madin-Darby canine kidney (MDCK) cells infected with A/California/04/2009 (H1N1pdm) pandemic strain, or A/Victoria/3/75 (H3N2), or the highly pathogenic avian influenza virus A/Vietnam/1203/2004 (H5N1) as immunosorbants we further show that the antibodies generated are also capable of binding to the homotetrameric form of M2 expressed on infected cells. Lethal challenge of vaccinated mice with A/California/04/2009 (H1N1pdm) pandemic strain, A/Victoria/3/75 (H3N2), and the highly pathogenic avian influenza virus A/Vietnam/1203/2004 (H5N1) led to 100%, 92%, and 100% protection, respectively. Overall, this study helps to lay the foundation of a potential universal influenza A vaccine.
Department of Chemical Engineering, Texas Tech University, Lubbock, TX 79409, USA.
Wenqian
W
Tao
Department of Animal, Dairy and Veterinary Sciences and the School of Veterinary Medicine, Utah State University, Logan, UT 84322, USA.
Brett L
BL
Hurst
Department of Chemical Engineering, Texas Tech University, Lubbock, TX 79409, USA.
Akhilesh Kumar
AK
Shakya
Department of Chemical Engineering, Texas Tech University, Lubbock, TX 79409, USA.
Md Jasim
MJ
Uddin
Department of Chemical Engineering, Texas Tech University, Lubbock, TX 79409, USA.
Rohan S J
RS
Ingrole
Center for Human Immunobiology, Department of Pediatrics, Texas Children's Hospital, Baylor College of Medicine, Houston, TX 77030, USA.
Mayra
M
Hernandez-Sanabria
Center for Human Immunobiology, Department of Pediatrics, Texas Children's Hospital, Baylor College of Medicine, Houston, TX 77030, USA.
Ravi P
RP
Arya
Center for Human Immunobiology, Department of Pediatrics, Texas Children's Hospital, Baylor College of Medicine, Houston, TX 77030, USA.
Lynn
L
Bimler
Center for Human Immunobiology, Department of Pediatrics, Texas Children's Hospital, Baylor College of Medicine, Houston, TX 77030, USA.
Silke
S
Paust
Department of Animal, Dairy and Veterinary Sciences and the School of Veterinary Medicine, Utah State University, Logan, UT 84322, USA.
E Bart
EB
Tarbet
Department of Chemical Engineering, Texas Tech University, Lubbock, TX 79409, USA. Electronic address: harvinder.gill@ttu.edu.
Harvinder Singh
HS
Gill
D000276:Adjuvants, Immunologic; D000281:Administration, Intranasal; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D056738:Cross Protection; D006046:Gold; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology; D053122:Influenza A Virus, H3N2 Subtype / Q000276:immunology; D053124:Influenza A Virus, H5N1 Subtype / Q000276:immunology; D009980:Influenza A virus / Q000276:immunology*; D007252:Influenza Vaccines / Q000008:administration & dosage / Q000276:immunology*; D053768:Metal Nanoparticles; D051379:Mice; D008807:Mice, Inbred BALB C; D009976:Orthomyxoviridae Infections / Q000517:prevention & control* / Q000821:virology; D014763:Viral Matrix Proteins / Q000737:chemistry / Q000276:immunology*; D000086082:Viroporin Proteins
D000276:Adjuvants, Immunologic; D000914:Antibodies, Viral; D006046:Gold; D007252:Influenza Vaccines; D014763:Viral Matrix Proteins; C488937:M2 protein, Influenza A virus; D000086082:Viroporin Proteins
Adjuvants; CpG; Gold nanoparticles; Influenza vaccine; Intranasal vaccination; M2e; Universal influenza vaccine