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TitleVaccination with prefusion-stabilized respiratory syncytial virus fusion protein induces genetically and antigenically diverse antibody responses.
Journal, issue, pagesImmunity, Vol. 54, Issue 4, Page 769-780.e6, Year 2021
Publish dateApr 13, 2021
AuthorsMaryam Mukhamedova / Daniel Wrapp / Chen-Hsiang Shen / Morgan S A Gilman / Tracy J Ruckwardt / Chaim A Schramm / Larissa Ault / Lauren Chang / Alexandrine Derrien-Colemyn / Sarah A M Lucas / Amy Ransier / Samuel Darko / Emily Phung / Lingshu Wang / Yi Zhang / Scott A Rush / Bharat Madan / Guillaume B E Stewart-Jones / Pamela J Costner / LaSonji A Holman / Somia P Hickman / Nina M Berkowitz / Nicole A Doria-Rose / Kaitlyn M Morabito / Brandon J DeKosky / Martin R Gaudinski / Grace L Chen / Michelle C Crank / John Misasi / Nancy J Sullivan / Daniel C Douek / Peter D Kwong / Barney S Graham / Jason S McLellan / John R Mascola /
PubMed AbstractAn 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) ...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.
External linksImmunity / PubMed:33823129 / PubMed Central
MethodsEM (single particle) / X-ray diffraction
Resolution2.9 - 3.21 Å
Structure data

23520

7luc

EMDB-23520, PDB-7luc:
Cryo-EM structure of RSV preF bound by Fabs 32.4K and 01.4B
Method: EM (single particle) / Resolution: 3.21 Å

23521

7lue

EMDB-23521, PDB-7lue:
Prefusion RSV F glycoprotein bound by neutralizing site V-directed antibody ADI-14442
Method: EM (single particle) / Resolution: 2.9 Å

PDB-7lud:
Crystal structure of Fab ADI-14442
Method: X-RAY DIFFRACTION / Resolution: 2.9 Å

Chemicals

ChemComp-SO4:
SULFATE ION / Sulfate

Source
  • respiratory syncytial virus
  • homo sapiens (human)
  • respiratory syncytial virus a2
KeywordsIMMUNE SYSTEM/VIRAL PROTEIN / RSV / viral fusogen / fusion protein / antibody / IMMUNE SYSTEM / IMMUNE SYSTEM-VIRAL PROTEIN complex / RSV F / Fab / Viral fusion protein / VIRAL PROTEIN/IMMUNE SYSTEM / fusion / immunoglobulin / public clonotype / convergent recognition / VIRAL PROTEIN / VIRAL PROTEIN-IMMUNE SYSTEM complex

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