Universal protection against influenza viruses by multi-subtype neuraminidase and M2 ectodomain virus-like particle
Fig 2
Vaccination with m-cNA-M2e VLP induces IgG antibodies specific for M2e, NA, multi subtype viruses, and broad NA inhibition activity.
(A) Schematic overview of vaccination of mice, prior to influenza virus challenge. BALB/c mice (n = 10 per group) were intramuscularly immunized twice with each VLP vaccine as indicated. Boost sera (W5) were used for measuring IgG, NAI, and ADCC assay, followed by intranasal (IN) influenza virus challenge at W7 and tissue samples were collected at day 5 or 6 post infection for lung viral titers. cN1: monomeric consensus cN1 NA VLP (3 μg), cN2: monomeric cN2 NA VLP (3 μg), 5xM2e: monomeric 5xM2e VLP (3 μg), m-cNA-M2e VLP: multi-subtype consensus NA (cN1-cN2-B cNA) plus 5xM2e VLP (10 μg). B cNA: monomeric consensus B NA VLP (3 μg). Naïve mice (PBS) were used as a mock control. (B-F) IgG antibodies in concentrations as determined by ELISA. IgG antibodies specific for M2e (B), N1 NA (A/Cal/2009 H1N1) (C), N2 NA (A/Brisbane/2007 H3N2) (D), inactivated influenza viruses (E and F) in boost immune sera. (G and H) Neuraminidase (NA) inhibition activities in 40-fold diluted boost immune sera by ELLA. rgA/PR8-Swz (rgAH1N2): reassortant containing N2 of A/Switzerland/2013 (H3N2) and A/PR8 (H1N1) backbone. All viruses and vaccine groups are as described in Materials and Methods. Data represented as mean ± SEM; statistical significances were performed by (B-D) one-way ANOVA and (E-H) Turkey’s comparison and two-way ANOVA with Bonferroni posttest and indicated as **, P < 0.01; ***, P < 0.001.