Use of N-trimethyl chitosan for intranasal delivery of DNA encoding M2e-HSP70c in mice

Authors

1 Department of Microbiology, Faculty of Veterinary Medicine, University of Tehran, Tehran, Iran

2 Research Center of Virus and Vaccine, Baqiyatallah University of Medical Sciences, Tehran, Iran

3 Department of Biotechnology, Razi Vaccine and Serum Research Institute (RVSRI), Karaj, Iran

4 Chemical Injuries Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran

5 Department of Virology, Tehran University of Medical Sciences, Tehran, Iran

Abstract

BACKGROUND: Influenza outbreak has become a great lifethreatening
disease in the world. Nasal vaccines can induce
systemic IgG and mucosal IgA antibody responses, which
establish two layers of immune defense against the infectious
pathogens like influenza. Mucosal vaccines must overcome
several limitations, including the mucociliary clearance and
inefficient uptake of soluble antigens. Therefore, nasal vaccines
require potent adjuvants and delivery systems. OBJECTIVES: In
this study we evaluated the effect of N-trimethyl chitosan (TMC)
as a potent vehicle for DNA encoding M2e/HSP70c in order for
intranasal administration in mice. METHODS:Ectodomain of the
conserved influenza matrix protein 2 (M2e), which has been
found to induce heterosubtypic immunity, was fused to
HSP70359-610 or C-terminus of Mycobacterium tuberculosis
HSP70 (HSP70c) in pcDNA3.1 vector (pcDNA/M2e-HSP70c)
and then encapsulated into a derivative of chitosan, N-trimethyl
chitosan (TMC). After encapsulation of the plasmid, physical
properties of the particles were investigated using Zetasizer®
3000 the particles were then administered through the intranasal
delivery in BALB/c mice. RESULTS: It was found that the
particles had a size ranging between 90-120nm and positive
surface charge. The intranasal immunization with M2e-
HSP70c+TMC in BALB/c mice significantly induced higher
M2e specific IgG than those induced in control groups
(pcDNA/M2e-HSP70c without TMC, pcDNA/M2e, bearing
M2e alone, and PBS).CONCLUSIONS: The present study showed
that the encapsulation of M2e/ HSP70c into N-trimethyl
chitosan (TMC) could strongly induce the humoral immune
response against the M2e-HSP70c plasmid without lowering the
adjuvant efficacy of HSP70c.

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