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Vaccination with prefusion-stabilized respiratory syncytial virus fusion protein induces genetically and antigenically diverse antibody responses.
Mukhamedova, Maryam; Wrapp, Daniel; Shen, Chen-Hsiang; Gilman, Morgan S A; Ruckwardt, Tracy J; Schramm, Chaim A; Ault, Larissa; Chang, Lauren; Derrien-Colemyn, Alexandrine; Lucas, Sarah A M; Ransier, Amy; Darko, Samuel; Phung, Emily; Wang, Lingshu; Zhang, Yi; Rush, Scott A; Madan, Bharat; Stewart-Jones, Guillaume B E; Costner, Pamela J; Holman, LaSonji A; Hickman, Somia P; Berkowitz, Nina M; Doria-Rose, Nicole A; Morabito, Kaitlyn M; DeKosky, Brandon J; Gaudinski, Martin R; Chen, Grace L; Crank, Michelle C; Misasi, John; Sullivan, Nancy J; Douek, Daniel C; Kwong, Peter D; Graham, Barney S; McLellan, Jason S; Mascola, John R.
Afiliación
  • Mukhamedova M; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA; Department of Biology, Johns Hopkins University, Baltimore, MD 21218, USA.
  • Wrapp D; Department of Molecular Biosciences, The University of Texas at Austin, Austin, TX 78712, USA.
  • Shen CH; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
  • Gilman MSA; Department of Molecular Biosciences, The University of Texas at Austin, Austin, TX 78712, USA.
  • Ruckwardt TJ; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
  • Schramm CA; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
  • Ault L; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
  • Chang L; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
  • Derrien-Colemyn A; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
  • Lucas SAM; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
  • Ransier A; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
  • Darko S; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
  • Phung E; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA; Institute for Biomedical Sciences, George Washington University, Washington, DC 20052, USA.
  • Wang L; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
  • Zhang Y; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
  • Rush SA; Department of Molecular Biosciences, The University of Texas at Austin, Austin, TX 78712, USA.
  • Madan B; Department of Pharmaceutical Chemistry, The University of Kansas, Lawrence, KS 66045, USA.
  • Stewart-Jones GBE; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
  • Costner PJ; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
  • Holman LA; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
  • Hickman SP; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
  • Berkowitz NM; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
  • Doria-Rose NA; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
  • Morabito KM; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
  • DeKosky BJ; Department of Pharmaceutical Chemistry, The University of Kansas, Lawrence, KS 66045, USA; Department of Chemical Engineering, The University of Kansas, Lawrence, KS 66045, USA.
  • Gaudinski MR; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
  • Chen GL; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
  • Crank MC; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
  • Misasi J; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
  • Sullivan NJ; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
  • Douek DC; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
  • Kwong PD; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
  • Graham BS; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
  • McLellan JS; Department of Molecular Biosciences, The University of Texas at Austin, Austin, TX 78712, USA.
  • Mascola JR; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA. Electronic address: jmascola@nih.gov.
Immunity ; 54(4): 769-780.e6, 2021 04 13.
Article en En | MEDLINE | ID: mdl-33823129
ABSTRACT
An effective vaccine for respiratory syncytial virus (RSV) is an unrealized public health goal. A single dose of the prefusion-stabilized fusion (F) glycoprotein subunit vaccine (DS-Cav1) substantially increases serum-neutralizing activity in healthy adults. We sought to determine whether DS-Cav1 vaccination induces a repertoire mirroring the pre-existing diversity from natural infection or whether antibody lineages targeting specific epitopes predominate. We evaluated RSV F-specific B cell responses before and after vaccination in six participants using complementary B cell sequencing methodologies and identified 555 clonal lineages. DS-Cav1-induced lineages recognized the prefusion conformation of F (pre-F) and were genetically diverse. Expressed antibodies recognized all six antigenic sites on the pre-F trimer. We identified 34 public clonotypes, and structural analysis of two antibodies from a predominant clonotype revealed a common mode of recognition. Thus, vaccination with DS-Cav1 generates a diverse polyclonal response targeting the antigenic sites on pre-F, supporting the development and advanced testing of pre-F-based vaccines against RSV.
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Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Virus Sincitial Respiratorio Humano / Infecciones por Virus Sincitial Respiratorio / Vacunas contra Virus Sincitial Respiratorio / Anticuerpos Antivirales / Formación de Anticuerpos Tipo de estudio: Clinical_trials / Etiology_studies / Incidence_studies / Observational_studies / Prognostic_studies / Risk_factors_studies Límite: Adolescent / Adult / Aged / Aged80 / Child / Child, preschool / Female / Humans / Infant / Male Idioma: En Año: 2021 Tipo del documento: Article

Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Virus Sincitial Respiratorio Humano / Infecciones por Virus Sincitial Respiratorio / Vacunas contra Virus Sincitial Respiratorio / Anticuerpos Antivirales / Formación de Anticuerpos Tipo de estudio: Clinical_trials / Etiology_studies / Incidence_studies / Observational_studies / Prognostic_studies / Risk_factors_studies Límite: Adolescent / Adult / Aged / Aged80 / Child / Child, preschool / Female / Humans / Infant / Male Idioma: En Año: 2021 Tipo del documento: Article