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 fof PIV1. We previously replaced the coding sequences for the hemagglutinin-neuraminidase (HN) and fusion (F) proteins of PIV3 with those of PIV1 in the PIV3 antigenomic cDNA. This was used to recover a fully-viable, recombinant chimeric PIV3-PIV1 virus, termed rPIV3-1, which bears the major protective antigens of PIV1 and is wild type-like with regard to growth in cell culture and in hamsters [Tao T, Durbin AP, Whitehead SS, Davoodi F, Collins PL, Murphy BR. Recovery of a fully viable chimeric human parainfluenza virus (PIV) type 3 in which the hemagglutinin-neuraminidase and fusion glycoprotein have been replaced by those of PIV type 1. J Virol 1998;72:2955-2961]. Here we report the recovery of a derivative of rPIV3-1 carrying the three temperature-sensitive and attenuating amino acid coding changes found in the L gene of the live-attenuated cp45 PIV3 candidate vaccine virus. This virus, termed rPIV3-1.cp45L, is temperature-sensitive with a shut-off temperature of 38 degrees C, which is similar to that of the recombinant rPIV3cp45L, which possesses the same three mutations. rPIV3-1.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 inducing a highly effective immune response against PIV1. It confirms previous observations that the surface glycoproteins of parainfluenza viruses are sufficient to induce a high level of resistance to homologous virus challenge. Unexpectedly, infection with recombinant chimeric virus rPIV3-1.cp45L or rPIV3-1, each bearing the surface glycoprotein genes of PIV1 and the internal genes of PIV3, also induced a moderate level 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 rodents, albeit a lower level of resistance than that induced by the surface glycoproteins. Thus, a reverse genetics system for PIV3 has been used successfully to produce a live attenuated PIV1 vaccine candidate that is attenuated and protective in experimental infection in hamsters.
Tao
T
T
Laboratory of Infectious Disease, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892-0720, USA. ttao@atlas.niaid.nih.gov
Skiadopoulos
M H
MH
Durbin
A P
AP
Davoodi
F
F
Collins
P L
PL
Murphy
B R
BR
D000818:Animals; D002460:Cell Line; D006224:Cricetinae; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000276:immunology; D006801:Humans; D007114:Immunization; D008647:Mesocricetus; D010222:Parainfluenza Virus 1, Human / Q000276:immunology* / Q000502:physiology; D010224:Parainfluenza Virus 3, Human / Q000276:immunology*; D011991:Receptors, Virus / Q000235:genetics / Q000276:immunology; D012137:Respiratory System / Q000821:virology; D013499:Surface Properties; D013696:Temperature; D014613:Vaccines, Attenuated / Q000276:immunology*; D014760:Viral Fusion Proteins / Q000276:immunology*; D014779:Virus Replication
C075739:F protein, parainfluenza virus 1; C039111:HN protein receptor; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D011991:Receptors, Virus; D014613:Vaccines, Attenuated; D014760:Viral Fusion Proteins; C072983:F protein, parainfluenza virus 3