{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,18]],"date-time":"2026-05-18T14:30:13Z","timestamp":1779114613237,"version":"3.51.4"},"reference-count":54,"publisher":"American Society for Microbiology","issue":"21","license":[{"start":{"date-parts":[[2016,11,1]],"date-time":"2016-11-01T00:00:00Z","timestamp":1477958400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/100000060","name":"HHS | NIH | National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["Intramural Program"],"award-info":[{"award-number":["Intramural Program"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["J Virol"],"published-print":{"date-parts":[[2016,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Human respiratory syncytial virus (RSV) and human parainfluenza virus type 3 (HPIV3) are major pediatric respiratory pathogens that lack vaccines. A chimeric bovine\/human PIV3 (rB\/HPIV3) virus expressing the unmodified, wild-type (wt) RSV fusion (F) protein from an added gene was previously evaluated in seronegative children as a bivalent intranasal RSV\/HPIV3 vaccine, and it was well tolerated but insufficiently immunogenic for RSV F. We recently showed that rB\/HPIV3 expressing a partially stabilized prefusion form (pre-F) of RSV F efficiently induced \u201chigh-quality\u201d RSV-neutralizing antibodies, defined as antibodies that neutralize RSV\n            <jats:italic>in vitro<\/jats:italic>\n            without added complement (B. Liang et al., J Virol 89:9499\u20139510, 2015, doi:10.1128\/JVI.01373-15). In the present study, we modified RSV F by replacing its cytoplasmic tail (CT) domain or its CT and transmembrane (TM) domains (TMCT) with counterparts from BPIV3 F, with or without pre-F stabilization. This resulted in RSV F being packaged in the rB\/HPIV3 particle with an efficiency similar to that of RSV particles. Enhanced packaging was substantially attenuating in hamsters (10- to 100-fold) and rhesus monkeys (100- to 1,000-fold). Nonetheless, TMCT-directed packaging substantially increased the titers of high-quality RSV-neutralizing serum antibodies in hamsters. In rhesus monkeys, a strongly additive immunogenic effect of packaging and pre-F stabilization was observed, as demonstrated by 8- and 30-fold increases of RSV-neutralizing serum antibody titers in the presence and absence of added complement, respectively, compared to pre-F stabilization alone. Analysis of vaccine-induced F-specific antibodies by binding assays indicated that packaging conferred substantial stabilization of RSV F in the pre-F conformation. This provides an improved version of this well-tolerated RSV\/HPIV3 vaccine candidate, with potently improved immunogenicity, which can be returned to clinical trials.\n          <\/jats:p>\n          <jats:p>\n            <jats:bold>IMPORTANCE<\/jats:bold>\n            Human respiratory syncytial virus (RSV) and human parainfluenza virus type 3 (HPIV3) are major viral agents of acute pediatric bronchiolitis and pneumonia worldwide that lack vaccines. A bivalent intranasal RSV\/HPIV3 vaccine candidate consisting of a chimeric bovine\/human PIV3 (rB\/HPIV3) strain expressing the RSV fusion (F) protein was previously shown to be well tolerated by seronegative children but was insufficiently immunogenic for RSV F. In the present study, the RSV F protein was engineered to be packaged efficiently into vaccine virus particles. This resulted in a significantly enhanced quantity and quality of RSV-neutralizing antibodies in hamsters and nonhuman primates. In nonhuman primates, this effect was strongly additive to the previously described stabilization of the prefusion conformation of the F protein. The improved immunogenicity of RSV F by packaging appeared to involve prefusion stabilization. These findings provide a potently more immunogenic version of this well-tolerated vaccine candidate and should be applicable to other vectored vaccines.\n          <\/jats:p>","DOI":"10.1128\/jvi.01196-16","type":"journal-article","created":{"date-parts":[[2016,9,1]],"date-time":"2016-09-01T00:21:41Z","timestamp":1472689301000},"page":"10022-10038","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":37,"title":["Packaging and Prefusion Stabilization Separately and Additively Increase the Quantity and Quality of Respiratory Syncytial Virus (RSV)-Neutralizing Antibodies Induced by an RSV Fusion Protein Expressed by a Parainfluenza Virus Vector"],"prefix":"10.1128","volume":"90","author":[{"given":"Bo","family":"Liang","sequence":"first","affiliation":[{"name":"RNA Viruses Section, Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, 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W.","family":"Dorward","sequence":"additional","affiliation":[{"name":"Rocky Mountain Laboratory, Microscopy Unit, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Emerito","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":[{"role":"author","vocabulary":"crossref"}]},{"given":"Natalie","family":"Mackow","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":[{"role":"author","vocabulary":"crossref"}]},{"given":"Barbora","family":"Kabatova","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":[{"role":"author","vocabulary":"crossref"}]},{"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":[{"role":"author","vocabulary":"crossref"}]},{"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":[{"role":"author","vocabulary":"crossref"}]},{"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":[{"role":"author","vocabulary":"crossref"}]},{"given":"Man","family":"Chen","sequence":"additional","affiliation":[{"name":"Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Syed M.","family":"Moin","sequence":"additional","affiliation":[{"name":"Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Azad","family":"Kumar","sequence":"additional","affiliation":[{"name":"Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jason 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