title: A live attenuated recombinant chimeric parainfluenza virus (PIV) candidate vaccine 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.
abstract: Using a reverse genetics system for PIV3, we previously recovered recombinant 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 and, surprisingly, also induced a moderate amount of restriction of the replication of PIV3 challenge virus. This suggested that some immunity is conferred by the internal PIV3 proteins shared by the two viruses. In the present study, we found that the immunity to PIV3 conferred by infection with rPIV3-1.cp45L is short-lived and completely disappeared four months after immunization, whereas resistance to replication of PIV3 induced by prior infection with PIV3 remains high even after an interval of four months. Since a live attenuated PIV1 vaccine such as the chimeric rPIV3-1.cp45L virus will likely be given to infants after a live attenuated PIV3 vaccine in a sequential immunization schedule, we examined the immunogenicity and efficacy of rPIV3-1.cp45L against PIV1 challenge in animals with and without prior immunity to PIV3. rPIV3-1.cp45L efficiently infected hamsters previously infected with wt or attenuated PIV3, but there was approximately a five-fold reduction 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 accompanied by a significant decrease in efficacy against PIV1 challenge. However, rPIV3-1.cp45L immunization of PIV3-immune animals induced a vigorous serum antibody response to PIV1 and reduced replication of PIV1 challenge virus 1000-fold in the lower respiratory tract and 25 to 200-fold in the upper respiratory tract. This study demonstrated that the recombinant chimeric rPIV3-1.cp45L candidate vaccine can induce immunity to PIV1 even in animals immune to PIV3. This establishes the feasibility of employing a sequential immunization schedule in which a recombinant chimeric rPIV3-1.cp45L vaccine is given following a live attenuated PIV3 vaccine.
authors.affiliation: Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 7 Center Drive MSC 0720, Bethesda, MD 20892, USA. ttao@niaid.nih.gov
authors.forename: T
authors.initials: T
authors.lastname: Tao
authors.forename: F
authors.initials: F
authors.lastname: Davoodi
authors.forename: C J
authors.initials: CJ
authors.lastname: Cho
authors.forename: M H
authors.initials: MH
authors.lastname: Skiadopoulos
authors.forename: A P
authors.initials: AP
authors.lastname: Durbin
authors.forename: P L
authors.initials: PL
authors.lastname: Collins
authors.forename: B R
authors.initials: BR
authors.lastname: Murphy
mesh_terms: D000818:Animals; D006224:Cricetinae; D005069:Evaluation Studies as Topic; D006388:Hemagglutinins / Q000276:immunology; D007114:Immunization; D008647:Mesocricetus; D009439:Neuraminidase / Q000276:immunology; D010222:Parainfluenza Virus 1, Human / Q000276:immunology*; D010223:Parainfluenza Virus 2, Human / Q000276:immunology; D010224:Parainfluenza Virus 3, Human / Q000276:immunology*; D011993:Recombinant Fusion Proteins / Q000276:immunology; D010253:Respirovirus Infections / Q000517:prevention & control*; D014613:Vaccines, Attenuated / Q000276:immunology; D014614:Vaccines, Synthetic / Q000276:immunology; D014760:Viral Fusion Proteins / Q000276:immunology; D014765:Viral Vaccines / Q000276:immunology / Q000627:therapeutic use*
chemical_list: D006388:Hemagglutinins; D011993:Recombinant Fusion Proteins; D014613:Vaccines, Attenuated; D014614:Vaccines, Synthetic; D014760:Viral Fusion Proteins; D014765:Viral Vaccines; D009439:Neuraminidase