New approaches for vaccination to prevent influenza virus
infection are needed. Emerging viruses, such as the H5N1 highly pathogenic
avian influenza (HPAI) virus, pose not only pandemic threats but also challenges in
vaccine development and production. Parainfluenza virus 5 (PIV5) is an appealing vector for
vaccine development, and we have previously shown that intranasal immunization with PIV5 expressing the
hemagglutinin from influenza virus was protective against influenza virus challenge (S. M. Tompkins, Y. Lin, G. P. Leser, K. A. Kramer, D. L. Haas, E. W. Howerth, J. Xu, M. J. Kennett, J. E. Durbin, R. A. Tripp, R. A. Lamb, and B. He, Virology 362:139-150, 2007). While intranasal immunization is an appealing approach, PIV5 may have the potential to be utilized in other formats, prompting us to test the efficacy of rPIV5-H5, which encodes the HA from H5N1 HPAI virus, in different vaccination schemes. In the BALB/c mouse model, a single intramuscular or intranasal immunization with a live rPIV5-H5 (ZL46) rapidly induced robust neutralizing serum antibody responses and protected against HPAI challenge, although mucosal
IgA responses primed by intranasal immunization more effectively controlled virus replication in the lung. The rPIV5-H5
vaccine incorporated the H5 HA into the virion, so we tested the efficacy of an inactivated form of the
vaccine. Inactivated rPIV5-H5 primed neutralizing serum antibody responses and controlled H5N1 virus replication; however, similar to other H5
antigen vaccines, it required a booster immunization to prime protective immune responses. Taken together, these results suggest that rPIV5-HA
vaccines and H5-specific
vaccines in particular can be utilized in multiple formats and by multiple routes of administration. This could avoid potential
contraindications based on
intranasal administration alone and provide opportunities for broader applications with the use of a single
vaccine vector.