A live attenuated chimeric recombinant parainfluenza virus (PIV) encoding the internal proteins of PIV type 3 and the surface glycoproteins of PIV type 1 induces complete resistance to PIV1 challenge and partial resistance to PIV3 challenge

The recovery of wild type and attenuated human parainfluenza type 3 (PIV3) recombinant viruses has made possible a new strategy to rapidly generate a live-attenuated vaccine virus for PIV1. We previously replaced the coding s equences for the hemagglutinin-neuraminidase (HN) and fusion (F) proteins o f PIV3 with those of PIV1 in the PIV3 antigenomic cDNA. This was used to re cover a fully-viable, recombinant chimeric PTV3-PIV1 virus, termed rPIV3-1, which bears the major protective antigens of PIV1 and is wild type-like wi th regard to growth in cell culture and in hamsters [Tao T, Durbin AP, Whit ehead SS, Davoodi F, Collins FL, Murphy BR. Recovery of a fully viable chim eric human parainfluenza virus (PIV) type 3 in which the hemagglutinin-neur aminidase and fusion glycoprotein have been replaced by those of PIV type I . J Virol 1998;72:2955-2961]. Here we report the recovery of a derivative o f rPIV3-1 carrying the three temperature-sensitive and attenuating amino ac id coding changes found in the L gene of the live-attenuated cp45 PIV3 cand idate vaccine virus. This virus, termed rPIV3-1.cp45L, is temperature-sensi tive with a shut-off temperature of 38 degrees C, which is similar to that of the recombinant rPIV3cp45L, which possesses the same three mutations. rP IV3-1.cp45L is attenuated in the respiratory tract of hamsters to the same extent as rPIV3cp45L. Infection of hamsters with rPIV3-1.cp45L generated a moderate level of hemagglutination-inhibiting antibodies against wild type PIV1 and induced complete resistance to challenge with wild type PIV1. This demonstrates that this novel attenuated chimeric virus is capable of induc ing a highly effective immune response against PIV1. It confirms previous o bservations that the surface glycoproteins of parainfluenza viruses are suf ficient to induce a high level of resistance to homologous virus challenge. Unexpectedly, infection with recombinant chimeric virus rPIV3-1.cp45L or r PIV3-1, each bearing the surface glycoprotein genes of PIV1 and the interna l genes of PIV3, also induced a moderate lever of resistance to replication of wild type PIV3 challenge virus. This indicates that the internal genes of PIV3 can independently induce protective immunity against PIV3 in rodent s, albeit a lower level of resistance than that induced by the surface glyc oproteins. Thus, a reverse genetics system for PIV3 has been used successfu lly to produce a live attenuated PIV1 vaccine candidate that is attenuated and protective in experimental infection in hamsters. Published by Elsevier Science Ltd.