Vaccination with self-adjuvanted protein nanoparticles provides protection against lethal influenza challenge.
Current influenza vaccines should be improved by the addition of universal influenza vaccine antigens in order to protect against multiple virus strains. We used our self-assembling protein nanoparticles (SAPNs) to display the two conserved influenza antigens M2e and Helix C in their native oligomerization states. To further improve the immunogenicity of the SAPNs, we designed and incorporated the TLR5 agonist flagellin into the SAPNs to generate self-adjuvanted SAPNs. We demonstrate that addition of flagellin does not affect the ability of SAPNs to self-assemble and that they are able to stimulate TLR5 in a dose-dependent manner. Chickens vaccinated with the self-adjuvanted SAPNs induce significantly higher levels of antibodies than those with unadjuvanted SAPNs and show higher cross-neutralizing activity compared to a commercial inactivated virus vaccine. Upon immunization with self-adjuvanted SAPNs, mice were completely protected against a lethal challenge. Thus, we have generated a self-adjuvanted SAPN with a great potential as a universal influenza vaccine.
Department of Molecular and Cell Biology, University of Connecticut, Storrs, CT, USA.
Christopher P
CP
Karch
Department of Pathobiology and Veterinary Science, University of Connecticut, Storrs, CT, USA.
Jianping
J
Li
Alpha-O Peptides AG, Riehen, Switzerland.
Caroline
C
Kulangara
Alpha-O Peptides AG, Riehen, Switzerland.
Sara M
SM
Paulillo
Alpha-O Peptides AG, Riehen, Switzerland.
Senthil K
SK
Raman
Institute of Materials Science, University of Connecticut, Storrs, CT, USA.
Sharareh
S
Emadi
Institute of Materials Science, University of Connecticut, Storrs, CT, USA.
Anmin
A
Tan
Department of Pathobiology and Veterinary Science, University of Connecticut, Storrs, CT, USA; Department of Microbiology and Immunology, Faculty of Pharmacy, Alazhar-University, Cairo, Egypt.
Zeinab H
ZH
Helal
Department of Pathobiology and Veterinary Science, University of Connecticut, Storrs, CT, USA; Department of Biotechnology, Guangxi Veterinary Research Institute, Nanning, Guangxi, China.
Qing
Q
Fan
Department of Pathobiology and Veterinary Science, University of Connecticut, Storrs, CT, USA. Electronic address: mazhar.khan@uconn.edu.
Mazhar I
MI
Khan
Department of Molecular and Cell Biology, University of Connecticut, Storrs, CT, USA; Alpha-O Peptides AG, Riehen, Switzerland; Institute of Materials Science, University of Connecticut, Storrs, CT, USA. Electronic address: peter.burkhard@uconn.edu.
Peter
P
Burkhard
D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000595:Amino Acid Sequence; D000818:Animals; D057134:Antibodies, Neutralizing / Q000097:blood; D000914:Antibodies, Viral / Q000097:blood; D000956:Antigens, Viral / Q000008:administration & dosage; D002645:Chickens; D004285:Dogs; D005408:Flagellin / Q000276:immunology; D053118:Influenza A Virus, H1N1 Subtype; D053125:Influenza A Virus, H5N2 Subtype; D007252:Influenza Vaccines / Q000008:administration & dosage / Q000276:immunology*; D061985:Madin Darby Canine Kidney Cells; D051379:Mice; D008807:Mice, Inbred BALB C; D008958:Models, Molecular; D053758:Nanoparticles / Q000008:administration & dosage / Q000737:chemistry*; D009976:Orthomyxoviridae Infections / Q000517:prevention & control*; D051198:Toll-Like Receptor 5 / Q000276:immunology; D014611:Vaccination
D000276:Adjuvants, Immunologic; D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D000956:Antigens, Viral; D007252:Influenza Vaccines; D051198:Toll-Like Receptor 5; D005408:Flagellin
Flagellin; Influenza; M2e; Nanoparticle; Vaccine