Immune response induced by the TAT-conjugated influenza M2e in mice

Matrix 2 protein ectodomain (M2e) of influenza virus appears to be a promising vaccine candidate because its sequence is highly conserved among virus strains. However, M2e is too meager to induce a strong immune response by itself. Several approaches are being used to increase the antigenicity of M2e. In an effort to enhance the M2e-specific immune response, we generated a TAT-conjugated M2e recombinant protein. Seven-week-old BALB/c mice were divided into three groups and transcutaneously immunized with 100 μg TAT-8×M2e (TAT conjugated with eight copies of M2e) and 8×M2e (eight copies of M2e) proteins on days 1, 15 and 29. The control mice were injected with PBS on the same days. Antibody titers specific for M2e were measured using indirect ELISA. Mice immunized with the TAT-8×M2e and 8×M2e proteins developed almost the same levels of M2e-specific total IgG and IgG1 antibodies. However, a higher level of M2e-specific IgG2a was observed in mice immunized with TAT-8×M2e than in those immunized with 8×M2e. These results suggest that TAT has an adjuvant effect that induces a Th1-type immune response. Therefore, the TAT-M2e vaccine can be applied to animals as a new influenza vaccine for enhancement of Th1-type immune responses.