This virus causes an acute and highly contagious respiratory disease. genes based on fusion PCR strategy and produced a fused fragment with 793 nucleotides. The construct was successfully cloned and expressed. Bottom line: This construct is a 261 amino acid chimeric fusion peptide with about 30 KD molecular weight. According around the latest information; this is the 1st case of expression and purification M2e-HA2 fusion chimeric peptide, which could be used to get development of a recombinant M2e-HA2 fusion protein vaccine. Keywords: Influenza, M2e, HA2, Cloning, Expression, Fusion PCR == Introduction GDC-0084 == Influenza disease IKK-alpha is an enveloped single-stranded negative-sense RNA virus, belongs to theOrthomyxoviridaefamily. This virus causes an acute and highly contagious respiratory disease. Seasonal epidemics of influenza disease cause serious illnesses and morbidity globally every year. Seasonal influenza each year: affects 5 to 15 percent of the world populace and causes 3 to 5 million serious infections. It is responsible for the death of up to 500 thousand patients globally. 1, 2Pandemic is the other face of this disease. Based on a prediction, possible pandemic of this disease would cause, up to 1 billion infections. 3According to the constant threat of a flu pandemic there is an urgent and serious need for developing antiviral strategies against the diverse influenza A viruses. Effective vaccination is one of the major ways to deal with the seasonal flu and the pandemic of this disease. Two major characterization of influenza disease; the error-prone polymerase and segmented genome cause antigenic drift and shift respectively. Antigenic drift induces variant in surface glycoproteins of virus, especially in hemagglutination (HA) and to a lower extent in neuraminidase (NA). Antigenic drift makes seasonal influenza vaccines inefficient. Antigenic shift causes genome segments dealing between the different subtypes of the disease and makes new genetic combinations. Antigenic shift could lead to horrible pandemics by emerging new viruses that can be transferable between different species. 4 The need for a vaccine protecting human being against almost all subtypes of influenza viruses including the reasons for future pandemics leads to a new universal influenza vaccine approach. To design such a vaccine, conserved areas of the disease proteins are GDC-0084 targeted. The candidate proteins should be guarded from the influence of genetic drift and yet can induce effective protection against influenza disease subtypes. External matrix protein 2 (M2e), hemagglutination 2 (HA2) and nucleoprotein (NP) are the most conserved proteins of the influenza virus A which have the previously told features. 5-7 M2 with 97 residues is the smallest protein of influenza disease. This type three or more trans- membrane protein acts as a pH regulated proton channel. 8, 9This function is effective in the beginning from the cell contamination and disease progeny formation. M2e the external domain name of the M2, only contains 32 protein residues. The unique characteristics of this domain, is that it is highly conserved, electronic. g. human being influenza disease M2e offers only up to five diverse position with avian M2e and therefore M2e human immune serum offers cross react with just about all varieties of avian M2e. 10The eight N-terminal residues of M2e (residues 2 to 9, SLLTEVET) is conserved in all subtypes of influenza A viruses. 11 ‘ with 556 residues is the most abundant protein GDC-0084 on influenza virus envelope. Cellular proteases cleave its precursor HA0 to HA1 and HA2, the cleavage is involved in the binding of virus to the cells surface, before access into the cells. 12The HA2 subunit (221 amino acids) has a curly hair spin-like structure composed of two antiparallel alpha-helixes. HA2 is more conserved than HA1, The hydrophobic N-terminal of the HA2 namely fusion peptide, especially its 1st 11 residues, is conserved among all influenza virus subtypes. 11It has been shown that antibodies against HA2 can safeguard mice against the challenge with viruses from different clades. 13 A suggested pattern in the design of Universal flu vaccines is constructing of fusion proteins based on a mix of different conserved epitopes of influenza disease proteins. This approach can preserve universality features and improve the safety and protection from the vaccine. Moreover, such an approach compared to vaccines targeting a single subunit antigen, reduces time and cost of production. 11 Based on the foregoing, considering well conserved sequences of M2e and HA2 and deficiencies in immunity induction in the use of single epitope (M2e or HA2), appears the chimeric antigens of these two, can features an effective universal influenza vaccine. In this present study we designed.