Construction of a live-attenuated bivalent vaccine virus against human parainfluenza virus (PIV) types 1 and 2 using a recombinant PIV3 backbone.
PIV1 and PIV2 are important agents of pediatric respiratory tract disease. We are developing live-attenuated vaccines against these viruses. We earlier constructed a PIV3/PIV1 antigenic chimeric virus, designated rPIV3-1, in which the hemagglutinin-neuraminidase (HN) and fusion (F) proteins of wild type rPIV3 were replaced by their PIV1 counterparts. In the present study, rPIV3-1 was used as a vector to express the HN protein of PIV2 to generate a single virus capable of inducing immunity to both PIV1 and PIV2. The PIV2 HN open reading frame was expressed from an extra gene cassette, under the control of PIV3 cis-acting transcription signals, inserted between the F and HN genes of rPIV3-1. The recombinant derivative, designated rPIV3-1.2HN, was readily recovered and exhibited a level of temperature sensitivity and in vitro growth similar to that of its parental virus. The rPIV3-1.2HN virus was restricted in replication in both the upper and lower respiratory tracts of hamsters compared with rPIV3-1, identifying an attenuating effect of the PIV2 HN insert in hamsters. rPIV3-1.2HN elicited serum antibodies to both PIV1 and PIV2 and induced resistance against challenge with wild type PIV1 or PIV2. Thus, rPIV3-1.2HN, a virus attenuated solely by the insertion of the PIV2 HN gene, functioned as a live attenuated bivalent vaccine candidate against both PIV1 and PIV2.
Tao
T
T
Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Building 7, Rm 106, 7 Center Drive MSC 0720, Bethesda, MD 20892, USA.
Skiadopoulos
M H
MH
Davoodi
F
F
Surman
S R
SR
Collins
P L
PL
Murphy
B R
BR
D000818:Animals; D002460:Cell Line; D006224:Cricetinae; D006801:Humans; D022241:Parainfluenza Vaccines / Q000096:biosynthesis* / Q000235:genetics / Q000627:therapeutic use; D010222:Parainfluenza Virus 1, Human / Q000235:genetics / Q000276:immunology*; D010223:Parainfluenza Virus 2, Human / Q000235:genetics / Q000276:immunology*; D010253:Respirovirus Infections / Q000517:prevention & control; D014613:Vaccines, Attenuated / Q000096:biosynthesis / Q000235:genetics / Q000627:therapeutic use; D019444:Vaccines, DNA / Q000096:biosynthesis* / Q000235:genetics / Q000627:therapeutic use; D014614:Vaccines, Synthetic / Q000096:biosynthesis / Q000627:therapeutic use
D022241:Parainfluenza Vaccines; D014613:Vaccines, Attenuated; D019444:Vaccines, DNA; D014614:Vaccines, Synthetic