Journal of Vaccines & Vaccination

Mucosal infl uenza vaccine comprising of M2e-HSP70 formulated with TMC nanoparticles induced strong M2e specifi c immune responses

International Conference & Exhibition on Vaccines & Vaccination

22-24 Nov 2011 Philadelphia Airport Marriott, USA

Mehran Dabaghian, Seyyed Mahmoud Ebrahimi, Gholamreza Nikbakht Brujeni, Majid Tebianian, Ali Rezaei Mokarram, Mahdi Fasihi Ramandi and Hamid Najminejad

Posters: J Vaccines Vaccin

Abstract:

Infl uenza outbreaks have become a great life-threatening disease in the world. Th e fi rst step in the viral entry is the binding of the hemagglutinin-neuraminidase (HN) to its receptor on respiratory epithelial cells. Nasal vaccines can induce systemic IgG and mucosal IgA antibody responses, which establish two layers of immune defense against infectious pathogens like infl uenza. Mucosal vaccines have to overcome several limitations, including mucociliary clearance and the ineffi cient uptake of soluble antigens. Th erefore, nasal vaccines require potent adjuvants and delivery systems to enhance their immunogenicity and to protect their antigens. In this study, ectodomain of the conserved infl uenza matrix protein 2 (M2e) which has been found to induce heterosubtypic immunity was fused to C-terminus of Mycobacterium tuberculosis (MBT) HSP70 and a derivative of chitosan, three methyl chitosan (TMC), was used as a carrier for this fusion protein. Chitosan is a biodegradable, nontoxic and mucoadhesive natural polymer that has immune adjuant eff ect and capable of opening the tight junctions between epithelial cells. Ionically crosslinked nanoparticles were formulated with M2e-HSP70 protein using the ionic gelation technique with pentasodium tripolyphospate (TPP) as a crosslinking agent. Nanoparticles showed high loading effi cacy and physical properties of nanoparticles was investigated using Zetasizer Nano particle analyzer (Malvern) and Transmission electron microscopy (TEM). Nanoparticles had a size in the range of 200-300nm and positive surface charge. TEM images revealed a spherical shape of nanoparticles. Intranasal immunization with M2e-HSP70/TMC in BALB/c mice induced signifi cantly higher M2e specifi c antibody, IgA in nasal secretions and IgG in serum, than those induced in control groups (M2e-HSP70, TMC and HSP70). Th e anti-M2e IgG subtype induced was mainly IgG2a. Cellular immune response was evaluated by cytokine production assay of splenocytes aft er in vitro stimulation. M2e-HSP70/TMC-immunized mice were fully protected against lethal challenge (MLD90) of infl uenza A infection (PR/8) compared to control groups of mice with survival rates of 20% to 30%. Th is data confi rmed that M2e-HSP70 fusion protein formulated with TMC nanoparticles could be an eff ective construct to induce strong immunogenicity and obtain full protection as a promising candidate mucosal infl uenza vaccine

Biography :

Dr. Mehran Dabaghian has completed his DVM degree at university of Tehran and now he is the student of immunology (Ph.D.) at university of Tehran, Iran. He is now conducting immunological parts of project on M2e- based in fl uenza A recombinant vaccine in Razi vaccine and serum research institute. His success is owed to his respected supervisors Dr. Seyyed Mahmoud Ebrahimi, Dr. Majid Tebianian, Dr.Gholamreza Nikbakht Brujeni and his coworker Dr. Mohammad Hossein Zabeh Jazi.