Abstract
Recombinant proteins bearing one (sM2) or three (3sM2) copies of M2 epitope from influenza virus were expressed in Escherichia coli. Mice were administrated with these two proteins and systemic and mucosal immune responses were analyzed. Compared with sM2, 3sM2 induced M2-specific serum IgG and mucosal IgA antibodies with neutralizing activity more efficiently in the whole immune course and the later mucosal immunization improved this advantage. MDCK cells pretreated with 3sM2 antisera showed less pathogenic morphological changes compared with that of pretreated with sM2. Together, our results demonstrated that high epitope density in one recombinant protein can enhance humoral immune responses in both systemic and mucosal immunization, and combination of systemic and mucosal immunization enhances this advantage.
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References
De Filette M, Fiers W, Martens W et al (2006) Improved design and intranasal delivery of an M2e-based human influenza A vaccine. Vaccine 24:6597–6601
De Filette M, Martens W, Smet A et al (2008) Universal influenza A M2e-HBc vaccine protects against disease even in the presence of pre-existing anti-HBc antibodies. Vaccine 26:6503–6507
Fan J, Liang X, Horton MS et al (2004) Preclinical study of influenza virus A M2 peptide conjugate vaccines in mice, ferrets, and rhesus monkeys. Vaccine 22:2993–3003
Feng J, Zhang M, Mozdzanowska K et al (2006) Influenza A virus infection engenders a poor antibody response against the ectodomain of matrix protein 2. Virol J 3:102
Frace AM, Klimov AI, Rowe T et al (1999) Modified M2 proteins produce heterotypic immunity against influenza A virus. Vaccine 17:2237–2244
Huang Z, Santi L, LePore K et al (2006) Rapid, high-level production of hepatitis B core antigen in plant leaf and its immunogenicity in mice. Vaccine 24:2506–2513
Liu W, Peng Z, Liu Z et al (2004) High epitope density in a single recombinant protein molecule of the extracellular domain of influenza A virus M2 protein significantly enhances protective immunity. Vaccine 23:366–371
Lu J, Guo Z, Pan X et al (2006) Passive immunotherapy for influenza A H5N1 virus infection with equine hyperimmune globulin F(ab′)2 in mice. Respir Res 7:43
Mozdzanowska K, Maiese K, Furchner M et al (1999) Treatment of influenza virus-infected SCID mice with nonneutralizing antibodies specific for the transmembrane proteins matrix 2 and neuraminidase reduces the pulmonary virus titer but fails to clear the infection. Virology 254:138–146
Mozdzanowska K, Feng J, Eid M et al (2003) Induction of influenza type A virus-specific resistance by immunization of mice with a synthetic multiple antigenic peptide vaccine that contains ectodomains of matrix protein 2. Vaccine 21:2616–2626
Neirynck S, Deroo T, Saelens X et al (1999) A universal influenza A vaccine based on the extracellular domain of the M2 protein. Nat Med 5:1157–1163
Pinto LH, Lamb RA (2006) The M2 proton channels of influenza A and B viruses. J Biol Chem 281:8997–9000
Schotsaert M, De Filette M, Fiers W et al (2009) Universal M2 ectodomain-based influenza A vaccines: preclinical and clinical developments. Expert Rev Vaccines 8:499–508
Tompkins SM, Zhao ZS, Lo CY et al (2007) Matrix protein 2 vaccination and protection against influenza viruses, including subtype H5N1. Emerg Infect Dis 13:426–435
Zharikova D, Mozdzanowska K, Feng J et al (2005) Influenza type A virus escape mutants emerge in vivo in the presence of antibodies to the ectodomain of matrix protein 2. J Virol 79:6644–6654
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This research was supported by a grant from National Natural Science Foundation of China (# 30771239).
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Pei, S., Xiong, N., Zhang, Y. et al. Increasing M2 epitope density enhances systemic and mucosal immune responses to influenza A virus. Biotechnol Lett 31, 1851–1856 (2009). https://doi.org/10.1007/s10529-009-0102-6
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DOI: https://doi.org/10.1007/s10529-009-0102-6