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Intranasal pediatric parainfluenza virus-vectored SARS-CoV-2 vaccine candidate is protective in macaques.
Nouën, Cyril Le; Nelson, Christine E; Liu, Xueqiao; Park, Hong-Su; Matsuoka, Yumiko; Luongo, Cindy; Santos, Celia; Yang, Lijuan; Herbert, Richard; Castens, Ashley; Moore, Ian N; Wilder-Kofie, Temeri; Moore, Rashida; Walker, April; Zhang, Peng; Lusso, Paolo; Johnson, Reed F; Garza, Nicole L; Via, Laura E; Munir, Shirin; Barber, Daniel; Buchholz, Ursula J.
Affiliation
  • Nouën CL; RNA Viruses Section, Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health; Bethesda, MD 20892, USA.
  • Nelson CE; These authors contributed equally to this work.
  • Liu X; T Lymphocyte Biology Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health; Bethesda, MD 20892, USA.
  • Park HS; These authors contributed equally to this work.
  • Matsuoka Y; RNA Viruses Section, Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health; Bethesda, MD 20892, USA.
  • Luongo C; RNA Viruses Section, Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health; Bethesda, MD 20892, USA.
  • Santos C; RNA Viruses Section, Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health; Bethesda, MD 20892, USA.
  • Yang L; RNA Viruses Section, Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health; Bethesda, MD 20892, USA.
  • Herbert R; RNA Viruses Section, Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health; Bethesda, MD 20892, USA.
  • Castens A; RNA Viruses Section, Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health; Bethesda, MD 20892, USA.
  • Moore IN; Experimental Primate Virology Section, Comparative Medicine Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health; Poolesville, MD 20837, USA.
  • Wilder-Kofie T; Experimental Primate Virology Section, Comparative Medicine Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health; Poolesville, MD 20837, USA.
  • Moore R; Comparative Medicine Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health; Bethesda, MD 20892, USA.
  • Walker A; Current address: Division of Pathology, Yerkes National Primate Research Center, Emory University; Atlanta, GA, 30329, USA.
  • Zhang P; Comparative Medicine Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health; Bethesda, MD 20892, USA.
  • Lusso P; Current Address: Division of Assurances, Office of Laboratory Animal Welfare, National Institutes of Health, MD 20892, USA.
  • Johnson RF; Comparative Medicine Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health; Bethesda, MD 20892, USA.
  • Garza NL; Current address: Yerkes National Primate Research Center, Environmental Health and Safety Office, Emory University; Atlanta, GA, 30322, USA.
  • Via LE; Tuberculosis Imaging Program, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health; Bethesda, MD 20892, USA.
  • Munir S; Viral Pathogenesis Section, Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health; Bethesda, MD 20892, USA.
  • Barber D; Viral Pathogenesis Section, Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health; Bethesda, MD 20892, USA.
  • Buchholz UJ; SARS-CoV-2 Virology Core, Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health; Bethesda, MD 20892, USA.
bioRxiv ; 2022 May 23.
Article in En | MEDLINE | ID: mdl-35665011
ABSTRACT
Pediatric SARS-CoV-2 vaccines are needed that elicit immunity directly in the airways, as well as systemically. Building on pediatric parainfluenza virus vaccines in clinical development, we generated a live-attenuated parainfluenza virus-vectored vaccine candidate expressing SARS-CoV-2 prefusion-stabilized spike (S) protein (B/HPIV3/S-6P) and evaluated its immunogenicity and protective efficacy in rhesus macaques. A single intranasal/intratracheal dose of B/HPIV3/S-6P induced strong S-specific airway mucosal IgA and IgG responses. High levels of S-specific antibodies were also induced in serum, which efficiently neutralized SARS-CoV-2 variants of concern. Furthermore, B/HPIV3/S-6P induced robust systemic and pulmonary S-specific CD4+ and CD8+ T-cell responses, including tissue-resident memory cells in lungs. Following challenge, SARS-CoV-2 replication was undetectable in airways and lung tissues of immunized macaques. B/HPIV3/S-6P will be evaluated clinically as pediatric intranasal SARS-CoV-2/parainfluenza virus type 3 vaccine.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Language: En Journal: BioRxiv Year: 2022 Type: Article Affiliation country: United States
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PubMed Links
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Full text: 1 Collection: 01-internacional Database: MEDLINE Language: En Journal: BioRxiv Year: 2022 Type: Article Affiliation country: United States