A live attenuated recombinant chimeric parainfluenza virus (PIV) candidatevaccine containing the hemagglutinin-neuraminidase and fusion glycoproteins of PIV1 and the remaining proteins from PIV3 induces resistance to PIV1 even in animals immune to PIV3

Using a reverse genetics system for PIV3, we previously recovered recombina nt chimeric PIV3-PIV1 virus bearing the major protective antigens of PIV1, the hemaglutinin-neuraminidase and fusion proteins, on a background of PIV3 genes bearing temperature sensitive (ts) and attenuating mutations in the L gene. Immunization of hamsters with this virus, designated rPIV3-1.cp45L, induced a high level of resistance to replication of wild type (wt) PIV1 a nd, surprisingly, also induced a moderate amount of restriction of the repl ication of PIV3 challenge virus. This suggested that some immunity is confe rred by the internal PIV3 proteins shared by the two viruses. In the presen t study, we found that the immunity to PIV3 conferred by infection with rPI V3-1.cp45L is short-lived and completely disappeared four months after immu nization, whereas resistance to replication of PIV3 induced by prior infect ion with PIV3 remains high even after an interval of four months. Since a l ive attenuated PIV1 vaccine such as the chimeric rPIV3-1.cp45L virus will l ikely be given to infants after a live attenuated PIV3 vaccine in a sequent ial immunization schedule, we examined the immunogenicity and efficacy of r PIV3-1.cp45L against PIV1 challenge in animals with and without prior immun ity to PIV3. rPIV3-1.cp45L efficiently infected hamsters previously infecte d with wt or attenuated PIV3, but there was approximately a five-fold reduc tion in replication of rPIV3-1.cp45L virus in the PIV3-immune animals. This reduction in replication of rPIV3-1.cp45L in PIV3-immune animals was accom panied by a significant decrease in efficacy against PIV1 challenge. Howeve r, rPIV3-1.cp45L immunization of PIV3-immune animals induced a vigorous ser um antibody response to PIV1 and reduced replication of PIV1 challenge viru s 1000-fold in the lower respiratory tract and 25 to 200-fold in the upper respiratory tract. This study demonstrated that the recombinant chimeric rP IV3-1.cp45L candidate vaccine can induce immunity to PIV1 even in animals i mmune to PIV3. This establishes the feasibility of employing a sequential i mmunization schedule in which a recombinant chimeric rPIV3-1.cp45L vaccine is given following a live attenuated PIV3 vaccine. Published by Elsevier Sc ience Ltd.