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

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; La Sonji 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

doi:10.1016/j.immuni.2021.03.004

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

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, La Sonji A. HolmanSomia 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

Research output: Contribution to journal › Article › peer-review

31 Scopus citations

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.

Original language	English
Pages (from-to)	769-780.e6
Journal	Immunity
Volume	54
Issue number	4
DOIs	https://doi.org/10.1016/j.immuni.2021.03.004
State	Published - 13 Apr 2021
Externally published	Yes

Keywords

RSV
antibody repertoire
cryo-EM structure
fusion glycoprotein
memory B cells
neutralizing antibodies
prefusion
public clonotypes
respiratory syncytial virus

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10.1016/j.immuni.2021.03.004

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Mukhamedova, M., Wrapp, D., Shen, C. H., Gilman, M. S. A., Ruckwardt, T. J., Schramm, C. A., Ault, L., Chang, L., Derrien-Colemyn, A., Lucas, S. A. M., Ransier, A., Darko, S., Phung, E., Wang, L., Zhang, Y., Rush, S. A., Madan, B., Stewart-Jones, G. B. E., Costner, P. J., ... Mascola, J. R. (2021). Vaccination with prefusion-stabilized respiratory syncytial virus fusion protein induces genetically and antigenically diverse antibody responses. Immunity, 54(4), 769-780.e6. https://doi.org/10.1016/j.immuni.2021.03.004

@article{52d9d1bfdf3a47b9aaf948347fa16632,

title = "Vaccination with prefusion-stabilized respiratory syncytial virus fusion protein induces genetically and antigenically diverse antibody responses",

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.",

keywords = "RSV, antibody repertoire, cryo-EM structure, fusion glycoprotein, memory B cells, neutralizing antibodies, prefusion, public clonotypes, respiratory syncytial virus",

author = "Maryam Mukhamedova and Daniel Wrapp and Shen, {Chen Hsiang} and Gilman, {Morgan S.A.} and Ruckwardt, {Tracy J.} and Schramm, {Chaim A.} and Larissa Ault and Lauren Chang and Alexandrine Derrien-Colemyn and Lucas, {Sarah A.M.} and Amy Ransier and Samuel Darko and Emily Phung and Lingshu Wang and Yi Zhang and Rush, {Scott A.} and Bharat Madan and Stewart-Jones, {Guillaume B.E.} and Costner, {Pamela J.} and Holman, {La Sonji A.} and Hickman, {Somia P.} and Berkowitz, {Nina M.} and Doria-Rose, {Nicole A.} and Morabito, {Kaitlyn M.} and DeKosky, {Brandon J.} and Gaudinski, {Martin R.} and Chen, {Grace L.} and Crank, {Michelle C.} and John Misasi and Sullivan, {Nancy J.} and Douek, {Daniel C.} and Kwong, {Peter D.} and Graham, {Barney S.} and McLellan, {Jason S.} and Mascola, {John R.}",

note = "Publisher Copyright: {\textcopyright} 2021",

year = "2021",

month = apr,

day = "13",

doi = "10.1016/j.immuni.2021.03.004",

language = "English",

volume = "54",

pages = "769--780.e6",

journal = "Immunity",

issn = "1074-7613",

publisher = "Cell Press",

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Mukhamedova, M, Wrapp, D, Shen, CH, Gilman, MSA, Ruckwardt, TJ, Schramm, CA, Ault, L, Chang, L, Derrien-Colemyn, A, Lucas, SAM, Ransier, A, Darko, S, Phung, E, Wang, L, Zhang, Y, Rush, SA, Madan, B, Stewart-Jones, GBE, Costner, PJ, Holman, LSA, Hickman, SP, Berkowitz, NM, Doria-Rose, NA, Morabito, KM, DeKosky, BJ, Gaudinski, MR, Chen, GL, Crank, MC, Misasi, J, Sullivan, NJ, Douek, DC, Kwong, PD, Graham, BS, McLellan, JS & Mascola, JR 2021, 'Vaccination with prefusion-stabilized respiratory syncytial virus fusion protein induces genetically and antigenically diverse antibody responses', Immunity, vol. 54, no. 4, pp. 769-780.e6. https://doi.org/10.1016/j.immuni.2021.03.004

TY - JOUR

T1 - Vaccination with prefusion-stabilized respiratory syncytial virus fusion protein induces genetically and antigenically diverse antibody responses

AU - Mukhamedova, Maryam

AU - Wrapp, Daniel

AU - Shen, Chen Hsiang

AU - Gilman, Morgan S.A.

AU - Ruckwardt, Tracy J.

AU - Schramm, Chaim A.

AU - Ault, Larissa

AU - Chang, Lauren

AU - Derrien-Colemyn, Alexandrine

AU - Lucas, Sarah A.M.

AU - Ransier, Amy

AU - Darko, Samuel

AU - Phung, Emily

AU - Wang, Lingshu

AU - Zhang, Yi

AU - Rush, Scott A.

AU - Madan, Bharat

AU - Stewart-Jones, Guillaume B.E.

AU - Costner, Pamela J.

AU - Holman, La Sonji A.

AU - Hickman, Somia P.

AU - Berkowitz, Nina M.

AU - Doria-Rose, Nicole A.

AU - Morabito, Kaitlyn M.

AU - DeKosky, Brandon J.

AU - Gaudinski, Martin R.

AU - Chen, Grace L.

AU - Crank, Michelle C.

AU - Misasi, John

AU - Sullivan, Nancy J.

AU - Douek, Daniel C.

AU - Kwong, Peter D.

AU - Graham, Barney S.

AU - McLellan, Jason S.

AU - Mascola, John R.

PY - 2021/4/13

Y1 - 2021/4/13

N2 - 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.

AB - 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.

KW - RSV

KW - antibody repertoire

KW - cryo-EM structure

KW - fusion glycoprotein

KW - memory B cells

KW - neutralizing antibodies

KW - prefusion

KW - public clonotypes

KW - respiratory syncytial virus

UR - http://www.scopus.com/inward/record.url?scp=85104369689&partnerID=8YFLogxK

U2 - 10.1016/j.immuni.2021.03.004

DO - 10.1016/j.immuni.2021.03.004

M3 - Article

C2 - 33823129

AN - SCOPUS:85104369689

SN - 1074-7613

VL - 54

SP - 769-780.e6

JO - Immunity

JF - Immunity

IS - 4

ER -

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

Abstract

Keywords

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