{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T09:46:06Z","timestamp":1784195166219,"version":"3.55.0"},"reference-count":45,"publisher":"American Society for Microbiology","issue":"20","license":[{"start":{"date-parts":[[2015,10,15]],"date-time":"2015-10-15T00:00:00Z","timestamp":1444867200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["J Virol"],"published-print":{"date-parts":[[2015,10,15]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Live attenuated recombinant human parainfluenza virus type 1 (rHPIV1) was investigated as a vector to express the respiratory syncytial virus (RSV) fusion (F) glycoprotein, to provide a bivalent vaccine against RSV and HPIV1. The RSV F gene was engineered to include HPIV1 transcription signals and inserted individually into three gene locations in each of the two attenuated rHPIV1 backbones. Each backbone contained a single previously described attenuating mutation that was stabilized against deattenuation, specifically, a non-temperature-sensitive deletion mutation involving 6 nucleotides in the overlapping P\/C open reading frames (ORFs) (C\n            <jats:sup>\u0394170<\/jats:sup>\n            ) or a temperature-sensitive missense mutation in the L ORF (L\n            <jats:sup>Y942A<\/jats:sup>\n            ). The insertion sites in the genome were pre-N (F1), N-P (F2), or P-M (F3) and were identical for both backbones.\n            <jats:italic>In vitro<\/jats:italic>\n            , the presence of the F insert reduced the rate of virus replication, but the final titers were the same as the final titer of wild-type (wt) HPIV1. High levels of RSV F expression in cultured cells were observed with rHPIV1-C\n            <jats:sup>\u0394170<\/jats:sup>\n            -F1, -F2, and -F3 and rHPIV1-L\n            <jats:sup>Y942A<\/jats:sup>\n            -F1. In hamsters, the rHPIV1-C\n            <jats:sup>\u0394170<\/jats:sup>\n            -F1, -F2, and -F3 vectors were moderately restricted in the nasal turbinates, highly restricted in lungs, and genetically stable\n            <jats:italic>in vivo<\/jats:italic>\n            . Among the C\n            <jats:sup>\u0394170<\/jats:sup>\n            vectors, the F1 virus was the most immunogenic and protective against wt RSV challenge. The rHPIV1-L\n            <jats:sup>Y942A<\/jats:sup>\n            vectors were highly restricted\n            <jats:italic>in vivo<\/jats:italic>\n            and were not detectably immunogenic or protective, indicative of overattenuation. The C\n            <jats:sup>\u0394170<\/jats:sup>\n            -F1 construct appears to be suitably attenuated and immunogenic for further development as a bivalent intranasal pediatric vaccine.\n          <\/jats:p>\n          <jats:p>\n            <jats:bold>IMPORTANCE<\/jats:bold>\n            There are no vaccines for the pediatric respiratory pathogens RSV and HPIV. We are developing live attenuated RSV and HPIV vaccines for use in virus-naive infants. Live attenuated RSV strains in particular are difficult to develop due to their poor growth and physical instability, but these obstacles could be avoided by the use of a vaccine vector. We describe the development and preclinical evaluation of live attenuated rHPIV1 vectors expressing the RSV F protein. Two different attenuated rHPIV1 backbones were each engineered to express RSV F from three different gene positions. The rHPIV1-C\n            <jats:sup>\u0394170<\/jats:sup>\n            -F1 vector, bearing an attenuating deletion mutation (C\n            <jats:sup>\u0394170<\/jats:sup>\n            ) in the P\/C gene and expressing RSV F from the pre-N position, was attenuated, stable, and immunogenic against the RSV F protein and HPIV1 in the hamster model and provided substantial protection against RSV challenge. This study provides a candidate rHPIV1-RSV-F vaccine virus suitable for continued development as a bivalent vaccine against two major childhood pathogens.\n          <\/jats:p>","DOI":"10.1128\/jvi.01380-15","type":"journal-article","created":{"date-parts":[[2015,7,30]],"date-time":"2015-07-30T02:55:30Z","timestamp":1438224930000},"page":"10319-10332","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":17,"title":["Attenuated Human Parainfluenza Virus Type 1 (HPIV1) Expressing the Fusion Glycoprotein of Human Respiratory Syncytial Virus (RSV) as a Bivalent HPIV1\/RSV Vaccine"],"prefix":"10.1128","volume":"89","author":[{"given":"Natalie","family":"Mackow","sequence":"first","affiliation":[{"name":"RNA Viruses Section, Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Em\u00e9rito","family":"Amaro-Carambot","sequence":"additional","affiliation":[{"name":"RNA Viruses Section, Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bo","family":"Liang","sequence":"additional","affiliation":[{"name":"RNA Viruses Section, Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sonja","family":"Surman","sequence":"additional","affiliation":[{"name":"RNA Viruses Section, Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthias","family":"Lingemann","sequence":"additional","affiliation":[{"name":"RNA Viruses Section, Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lijuan","family":"Yang","sequence":"additional","affiliation":[{"name":"RNA Viruses Section, Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter L.","family":"Collins","sequence":"additional","affiliation":[{"name":"RNA Viruses Section, Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shirin","family":"Munir","sequence":"additional","affiliation":[{"name":"RNA Viruses Section, Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(10)60206-1"},{"key":"e_1_3_2_3_2","first-page":"1497","volume-title":"Fields virology","author":"Karron RA","year":"2007","unstructured":"Karron RA, Collins PL. 2007. 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