title: Synthesis and Immunogenicity Assessment of Elastin-Like Polypeptide-M2e Construct as an Influenza Antigen.
abstract: The 23 amino acid-long extracellular domain of the influenza virus transmembrane protein M2 (M2e) has remained highly conserved since the 1918 pandemic, and is thus considered a good candidate for development of a universal influenza A vaccine. However, M2e is poorly immunogenic. In this study we assessed the potential of increasing immunogenicity of M2e by constructing a nanoscale-designed protein polymer containing the M2e sequence and an elastin-like polypeptide (ELP) nanodomain consisting of alanine and tyrosine guest residues (ELP(A2YA2)24). The ELP nanodomain was included to increase antigen size, and to exploit the inherent thermal inverse phase transition behavior of ELPs to purify the protein polymer. The ELP(A2YA2)24+ M2e nanodomained molecule was recombinantly synthesized. Characterization of its inverse phase transition behavior demonstrated that attachment of M2e to ELP(A2YA2)24increased its transition temperature compared to ELP(A2YA2)24. Using a dot blot test we determined that M2e conjugated to ELP is recognizable by M2e-specific antibodies, suggesting that the conjugation process does not adversely affect the immunogenic property of M2e. Further, upon vaccinating mice with ELP(A2YA2)24+ M2e it was found that indeed the nanodomained protein enhanced M2e-specific antibodies in mouse serum compared to free M2e peptide and ELP(A2YA2)24. The immune serum could also recognize M2 expressed on influenza virions. Overall, this data suggests the potential of using molecules containing M2e-ELP nano-domains to develop a universal influenza vaccine.
authors.affiliation: Department of Chemical Engineering Texas Tech University, 6th and Canton Lubbock, Texas 79409, USA.
authors.forename: Rohan S
authors.initials: RS
authors.lastname: Ingrole
authors.affiliation: Department of Chemical Engineering Texas Tech University, 6th and Canton Lubbock, Texas 79409, USA.
authors.forename: Wenqian
authors.initials: W
authors.lastname: Tao
authors.affiliation: Center for Biotechnology and Genomics Texas Tech University Lubbock, Texas 79409, USA.
authors.forename: Jatindra N
authors.initials: JN
authors.lastname: Tripathy
authors.affiliation: Department of Chemical Engineering Texas Tech University, 6th and Canton Lubbock, Texas 79409, USA.
authors.forename: Harvinder S
authors.initials: HS
authors.lastname: Gill
keywords: Elastin-like polypeptide; M2e fusion protein; M2e vaccine; influenza vaccine; universal influenza vaccine
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