Influenza A Vaccine Analysis

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Influenza A viruses, members of Ortomyxoviridae family, are capable of infecting a large variety of animals as well as humans. Hemagglutinin (HA) and neuraminidase (NA) are the most abundant proteins on the viral surface. Thus far eighteen different HAs (H1 to H18) and eleven NAs (N1 to N11) have been distinguished serologically and are currently used for nomenclature of subtypes. Due to segmented genome, zoonotic nature and appearance of continuous mutation resulting in genome replication by the high error-rate RNA polymerase, Influenza A viruses are able to increase or change their epidemic or pandemic feature. This rapid evolution in Influenza genome raises the need of updating vaccine formulations annually to include new viral antigens …show more content…

Thus, the development of a universal vaccine that provides cross-protection against all variant subtypes of influenza A virus has drawn more attention in recent decades [11-15]. These include vaccines that induce antibodies directed against more conserved sequences like nucleoprotein (NP), HA2 region of the stalk domain, and matrix protein 2 ectodomains (M2e) [12, 16-19].
On the other hand, mass production of these virus-based influenza vaccines requires large-scale mammalian cell culture or large source of embryo eggs. These systems are costly and not rapid enough to match with a newly emerged influenza strain as witnessed in the 2009 H1N1 outbreak [20-24].
Since 1999, several studies have demonstrated that M2e vaccine candidates explored in different ways including baculovirus-expressed M2 [25], fusion proteins [26-28], and multiple antigenic peptides [29] could protect animals well against challenge with homologous or heterologous viruses, and even the heterosubtypic …show more content…

This homotetramer protein with 97 amino acids in each monomer comprises a short region in N-terminal ecto domain, a transmembrane domain and a long protein molecule which have ion channel activity and regulate vesicular and cytoplasmic pH within the virus-infected cells [32, 33]. M2 ecto domain which is known as M2e, include 24 amino acids from N-terminal which remained highly conserved. Moreover, another region of the N-terminal which includes 2 to 9 amino acids that is famous as SLLTEVET epitope is conserved among all influenza A subtypes. Considering the existence of such conserved epitopes in M2, this region seems to be a reasonable choice for designing the universal vaccine [34]. Nevertheless, the point is that M2e conserved region is not large enough to trigger immune response alone. This problem has been solved by fusing different types of molecular adjuvants like HBc, ASP-1, CTA1-DD and bacterial flagellin [35-38].
Among gram-positive bacteria, Bacillus subtilis has been developed as an attractive host for the expression of foreign proteins with pharmacological or immunological activities. In contrast to gram-negative E.coli, this bacterium contains no lipopolysaccharides (LPS) in the outer cell membrane. In addition, it has a naturally high secretory capacity and exports proteins directly into the extracellular medium, which simplifies downstream

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