Sendai virus recombinant vaccine expressing hPIV-3 HN or F elicits protective immunity and combines with a second recombinant to prevent hPIV-1, hPIV-3 and RSV infections

Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, TN 38105, United States.
Vaccine (Impact Factor: 3.62). 07/2008; 26(27-28):3480-8. DOI: 10.1016/j.vaccine.2008.04.022
Source: PubMed


The human parainfluenza viruses (hPIVs) and respiratory syncytial virus (RSV) are the leading causes of serious respiratory illness in the human pediatric population. Despite decades of research, there are currently no licensed vaccines for either the hPIV or RSV pathogens. Here we describe the testing of hPIV-3 and RSV candidate vaccines using Sendai virus (SeV, murine PIV-1) as a vector. SeV was selected as the vaccine backbone, because it has been shown to elicit robust and durable immune activities in animal studies, and has already advanced to human safety trials as a xenogenic vaccine for hPIV-1. Two new SeV-based hPIV-3 vaccine candidates were first generated by inserting either the fusion (F) gene or hemagglutinin-neuraminidase (HN) gene from hPIV-3 into SeV. The resultant rSeV-hPIV3-F and rSeV-hPIV3-HN vaccines expressed their inserted hPIV-3 genes upon infection. The inoculation of either vaccine into cotton rats elicited binding and neutralizing antibody activities, as well as interferon-gamma-producing T cells. Vaccination of cotton rats resulted in protection against subsequent challenges with either homologous or heterologous hPIV-3. Furthermore, vaccination of cotton rats with a mixture of rSeV-hPIV3-HN and a previously described recombinant SeV expressing the F protein of RSV resulted in protection against three different challenge viruses: hPIV-3, hPIV-1 and RSV. Results encourage the continued development of the candidate recombinant SeV vaccines to combat serious respiratory infections of children.

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    • "The full genome cDNA of rSeV (pSeV(E), strain Enders) [39] was mutated at the non-coding regions between M and F, F and HN, and HN and L to include unique restriction sites for FseI, NotI, and AscI, respectively. The SeV HN and F genes in pSeV(E) were replaced with those of hPIV1 HN and F cDNAs produced by PCR using primers containing appropriate restriction sites. "
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    • "Since Sendai virus is a murine parainfluenza virus (PIV) with certain homologies to human PIV, it was tested as xenotropic vaccine in African Green monkeys and humans without any significant adverse reactions [34] [35]. Recombinant SeV vector carrying human PIV was also tested in rats [36] [37]. Further, recombinant SeV vaccine for human immunodeficiency virus (HIV) infection is going to be tested in humans ( "
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    • "The full genome cDNA of rSeVLeGFP (pSeVLeGFP) was constructed as follows. The cDNA containing the L protein C-terminus was subcloned from pSeV(E) [57] to plasmid pTF1 [58] and an FseI site was created at the end of the L coding region using the QuikChange Mutagenesis Kit (Stratagene). The eGFP gene was amplified by PCR from plasmid pEGFP-N1 (Clontech) using primers containing FseI sites flanking the gene, and was inserted into the L gene fragment in pTF1 at the FseI site. "
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