Abstract
BackgroundImmunity to conserved viral antigens is an attractive approach to develop a universal vaccine against epidemic and pandemic influenza. A nucleoprotein (NP)-based vaccine has been explored and preliminary studies have shown promise. However, no study has explored the immunity and cross-protective efficacy of recombinant NP derived from Escherichia coli compared with recombinant vaccinia virus (Tiantan).MethodsRecombinant NP protein (rNP) from influenza virus A/Jingke/30/95(H3N2) was obtained from E. coli and recombinant vaccinia virus (Tiantan) RVJ1175NP. Purified rNP without adjuvant and RVJ1175NP were used to immunize BALB/c mice intramuscularly. Humoral immune responses were detected by ELISA, while cell-mediated immune responses were measured by ex vivo IFN-γ ELISPOT and in vivo cytotoxicity assays. The cross-protective efficacy was assessed by a challenge with a heterosubtype of influenza virus A/PR/8/34(H1N1).ResultsOur results demonstrate that a high dose (90 μg) of rNP induced NP-specific antibodies and T cell responses that were comparable with those of RVJ1175NP in mice. Importantly, the survival ratio (36, 73, and 78%) of the vaccinated mice after the influenza virus A/PR/8/34(H1N1) challenge was rNP vaccine dose-dependent (10, 30, and 90 μg, respectively), and no significant differences were observed between the rNP- and RVJ1175NP-immunized (91%) mice.ConclusionsInfluenza A virus NP derived from E. coli or recombinant vaccinia (Tiantan) virus elicited cross-protection against influenza virus in mice, and the immune response and protective efficacy of rNP were comparable to RVJ1175NP. These data provide a basis for the use of prokaryotically expressed NP as a candidate universal influenza vaccine.
Highlights
Immunity to conserved viral antigens is an attractive approach to develop a universal vaccine against epidemic and pandemic influenza
Characterization of Recombinant NP protein (rNP) purified from E. coli or RVJ1175NP To assess the efficacy of rNP expressed in E. coli as a candidate universal influenza vaccine, we constructed an expression plasmid, pET30a-NP, to express rNP of influenza A/Jingke/30/95(H3N2) in E. coli BL21(DE3) (Figure 1A), as well as a recombinant vaccinia virus RVJ1175NP expressing NP (Figure 1D)
Our results demonstrate that a high dose of rNP induced comparable anti-NP antibody and T cell responses to RVJ1175NP in mice
Summary
Immunity to conserved viral antigens is an attractive approach to develop a universal vaccine against epidemic and pandemic influenza. Licensed influenza vaccines are trivalent live attenuated or inactivated killed virus vaccines, consisting of three strains of each virus (influenza A H1N1 and H3N2 and one influenza B) thought to be most prevalent in the upcoming influenza season [4,5] These vaccines elicit neutralizing antibodies against the highly variable hemagglutinin (HA) of influenza virus, providing protection against homologous but non-antigenically distinct heterologous viruses. These vaccines must be frequently reformulated to match the circulating strains [6,7]. The development of a vaccine that induces cross-protection against variant subtypes of influenza A virus and which can be produced quickly at high quantities is desirable
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