ジャーナル: Immunity / 年: 2021 タイトル: Vaccination with prefusion-stabilized respiratory syncytial virus fusion protein induces genetically and antigenically diverse antibody responses. 著者: Maryam 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 / ...著者: Maryam 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 / 要旨: 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) ...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.
A: Fusion glycoprotein F0 B: Fusion glycoprotein F0 C: Fusion glycoprotein F0 D: 01.4B Fab Heavy chain E: 01.4B Fab Light chain F: 01.4B Fab Heavy chain G: 01.4B Fab Light chain H: 01.4B Fab Heavy chain I: 01.4B Fab Light chain J: 32.4K Fab Heavy chain K: 32.4K Fab Light chain L: 32.4K Fab Heavy chain M: 32.4K Fab Light chain N: 32.4K Fab Heavy chain O: 32.4K Fab Light chain