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Synthesis and Immunogenicity Assessment of Elastin-Like Polypeptide-M2e Construct as an Influenza Antigen

tetano

Editor, Senior Moderator
Nano Life. 2014 Jun 1;4(2):1450004.
[h=1]Synthesis and Immunogenicity Assessment of Elastin-Like Polypeptide-M2e Construct as an Influenza Antigen.[/h] Ingrole RS[SUP]1[/SUP], Tao W[SUP]1[/SUP], Tripathy JN[SUP]2[/SUP], Gill HS[SUP]1[/SUP].
[h=3]Author information[/h]

[h=3]Abstract[/h] 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(A[SUB]2[/SUB]YA[SUB]2[/SUB])[SUB]24[/SUB]). 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(A[SUB]2[/SUB]YA[SUB]2[/SUB])[SUB]24[/SUB] + M2e nanodomained molecule was recombinantly synthesized. Characterization of its inverse phase transition behavior demonstrated that attachment of M2e to ELP(A[SUB]2[/SUB]YA[SUB]2[/SUB])[SUB]24[/SUB] increased its transition temperature compared to ELP(A[SUB]2[/SUB]YA[SUB]2[/SUB])[SUB]24[/SUB]. 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(A[SUB]2[/SUB]YA[SUB]2[/SUB])[SUB]24[/SUB] + M2e it was found that indeed the nanodomained protein enhanced M2e-specific antibodies in mouse serum compared to free M2e peptide and ELP(A[SUB]2[/SUB]YA[SUB]2[/SUB])[SUB]24[/SUB]. 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.


[h=4]KEYWORDS:[/h] Elastin-like polypeptide; M2e fusion protein; M2e vaccine; influenza vaccine; universal influenza vaccine

PMID: 25825595 [PubMed]
 
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