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Clin Vaccine Immunol. 2012 May 30. [Epub ahead of print]
Enhanced influenza VLP vaccines containing M2e and a TLR ligand.
Wang BZ, Gill HS, Kang SM, Wang L, Wang YC, Vassilieva EV, Compans RW.
Source
Department of Microbiology and Immunology and Emory Vaccine Center Emory University School of Medicine 1518 Clifton Road, Atlanta, Georgia 30322.
Abstract
M2e is the external domain of the matrix protein 2 (M2) and is conserved amongst influenza A viruses. The goal of this project is to develop enhanced influenza vaccines with broad protective efficacy using the M2e antigen. We designed a membrane-anchored fusion protein by replacing the hyperimmunogenic region of Salmonella typhimurium flagellin (FliC) with four repeats of M2e (4.M2e-tFliC) and fusing to a membrane-anchor from influenza hemagglutinin (HA). The fusion protein was incorporated into influenza M1 virus-like particles (VLPs). These VLPs retained TLR5 agonist activity comparable to that of soluble FliC. Mice immunized with the VLPs by either intramuscular or intranasal immunization showed high levels of systemic M2-specific antibody responses compared to soluble 4.M2e protein. High mucosal antibody titers were also induced in intranasally immunized mice. All intranasally immunized mice survived lethal live virus challenges while intramuscularly immunized mice showed only partial protection, revealing better protection by the intranasal route. These results indicate that a combination of M2e antigens and TLR ligand adjuvants in VLPs has potential for development of a broadly protective influenza A vaccine.
PMID:
22647270
[PubMed - as supplied by publisher]
Enhanced influenza VLP vaccines containing M2e and a TLR ligand.
Wang BZ, Gill HS, Kang SM, Wang L, Wang YC, Vassilieva EV, Compans RW.
Source
Department of Microbiology and Immunology and Emory Vaccine Center Emory University School of Medicine 1518 Clifton Road, Atlanta, Georgia 30322.
Abstract
M2e is the external domain of the matrix protein 2 (M2) and is conserved amongst influenza A viruses. The goal of this project is to develop enhanced influenza vaccines with broad protective efficacy using the M2e antigen. We designed a membrane-anchored fusion protein by replacing the hyperimmunogenic region of Salmonella typhimurium flagellin (FliC) with four repeats of M2e (4.M2e-tFliC) and fusing to a membrane-anchor from influenza hemagglutinin (HA). The fusion protein was incorporated into influenza M1 virus-like particles (VLPs). These VLPs retained TLR5 agonist activity comparable to that of soluble FliC. Mice immunized with the VLPs by either intramuscular or intranasal immunization showed high levels of systemic M2-specific antibody responses compared to soluble 4.M2e protein. High mucosal antibody titers were also induced in intranasally immunized mice. All intranasally immunized mice survived lethal live virus challenges while intramuscularly immunized mice showed only partial protection, revealing better protection by the intranasal route. These results indicate that a combination of M2e antigens and TLR ligand adjuvants in VLPs has potential for development of a broadly protective influenza A vaccine.
PMID:
22647270
[PubMed - as supplied by publisher]
