Vaccination with prefusion-stabilized respiratory syncytial virus fusion protein induces genetically and antigenically diverse antibody responses.

Apr 8, 2021

Contributor: 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

Vaccination with prefusion-stabilized respiratory syncytial virus fusion protein induces genetically and antigenically diverse antibody responses.

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.
Published by Elsevier Inc.

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About The Expert

Maryam Mukhamedova

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.

Daniel Wrapp

Department of Molecular Biosciences, The University of Texas at Austin, Austin, TX 78712, USA.

Chen-Hsiang Shen

Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.

Morgan S A Gilman

Department of Molecular Biosciences, The University of Texas at Austin, Austin, TX 78712, USA.

Tracy J Ruckwardt

Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.

Chaim A Schramm

Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.

Larissa Ault

Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.

Lauren Chang

Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.

Alexandrine Derrien-Colemyn

Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.

Sarah A M Lucas

Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.

Amy Ransier

Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.

Samuel Darko

Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.

Emily Phung

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.

Lingshu Wang

Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.

Yi Zhang

Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.

Scott A Rush

Department of Molecular Biosciences, The University of Texas at Austin, Austin, TX 78712, USA.

Bharat Madan

Department of Pharmaceutical Chemistry, The University of Kansas, Lawrence, KS 66045, USA.

Guillaume B E Stewart-Jones

Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.

Pamela J Costner

Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.

LaSonji A Holman

Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.

Somia P Hickman

Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.

Nina M Berkowitz

Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.

Nicole A Doria-Rose

Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.

Kaitlyn M Morabito

Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.

Brandon J DeKosky

Department of Pharmaceutical Chemistry, The University of Kansas, Lawrence, KS 66045, USA; Department of Chemical Engineering, The University of Kansas, Lawrence, KS 66045, USA.

Martin R Gaudinski

Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.

Grace L Chen

Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.

Michelle C Crank

Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.

John Misasi

Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.

Nancy J Sullivan

Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.

Daniel C Douek

Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.

Peter D Kwong

Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.

Barney S Graham

Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.

Jason S McLellan

Department of Molecular Biosciences, The University of Texas at Austin, Austin, TX 78712, USA.

John R Mascola

Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA. Electronic address: jmascola@nih.gov.

References

PubMed