Efficacy of parainfluenza virus 5 mutants expressing hemagglutinin from H5N1 influenza A virus in mice

Parainfluenza virus 5 (PIV5) is a promising viral vector for vaccine development. PIV5 is safe, stable, efficacious, cost-effective to produce and, most interestingly, it overcomes preexisting antivector immunity. We have recently reported that PIV5 expressing the hemagglutinin (HA) from highly pathogenic avian influenza (HPAI) virus H5N1 (PIV5-H5) provides sterilizing immunity against lethal doses of HPAI H5N1 infection in mice. It is thought that induction of apoptosis can lead to enhanced antigen pre-sentation. Previously, we have shown that deleting the SH gene and the conserved C terminus of the V gene in PIV5 results in mutant viruses (PIV5SH and PIV5VC) that enhance induction of apoptosis. In this study, we inserted the HA gene of H5N1 into PIV5SH (PIV5SH-H5) or PIV5VC (PIV5VC-H5) and compared their efficacies as vaccine candidates to PIV5-H5.We have found that PIV5SH-H5 induced the highest levels of anti-HA antibodies, the strongest T cell responses, and the best pro-tection against an H5N1 lethal challenge in mice. These results suggest that PIV5SH is a better vaccine vector than wild-type PIV5. Parainfluenza virus 5 (PIV5), a nonsegmented negative-sensesingle-stranded RNA virus, is a member of the genus Rubula-virus of the family Paramyxoviridae (1). Several characteristics of PIV5 make it an attractive vaccine candidate vector. First, PIV5 is thought to be a contributing factor for kennel cough (2–6), and kennel cough vaccines containing live PIV5 have been used i