A COVID-19 vaccine candidate using SpyCatcher multimerization of the SARS-CoV-2 spike protein receptor-binding domain induces potent neutralising antibody responses

Tiong Kit Tan; Pramila Rijal; Rolle Rahikainen; Anthony H. Keeble; Lisa Schimanski; Saira Hussain; Ruth Harvey; Jack W.P. Hayes; Jane C. Edwards; Rebecca K. McLean; Veronica Martini; Miriam Pedrera; Nazia Thakur; Carina Conceicao; Isabelle Dietrich; Holly Shelton; Anna Ludi; Ginette Wilsden; Clare Browning; Adrian K. Zagrajek; Dagmara Bialy; Sushant Bhat; Phoebe Stevenson-Leggett; Philippa Hollinghurst; Matthew Tully; Katy Moffat; Chris Chiu; Ryan Waters; Ashley Gray; Mehreen Azhar; Valerie Mioulet; Joseph Newman; Amin S. Asfor; Alison Burman; Sylvia Crossley; John A. Hammond; Elma Tchilian; Bryan Charleston; Dalan Bailey; Tobias J. Tuthill; Simon P. Graham; Helen M.E. Duyvesteyn; Tomas Malinauskas; Jiandong Huo; Julia A. Tree; Karen R. Buttigieg; Raymond J. Owens; Miles W. Carroll; Rodney S. Daniels; John W. McCauley; David I. Stuart; Kuan Ying A. Huang; Mark Howarth; Alain R. Townsend

doi:10.1038/s41467-020-20654-7

A COVID-19 vaccine candidate using SpyCatcher multimerization of the SARS-CoV-2 spike protein receptor-binding domain induces potent neutralising antibody responses

Tiong Kit Tan^*, Pramila Rijal, Rolle Rahikainen, Anthony H. Keeble, Lisa Schimanski, Saira Hussain, Ruth Harvey, Jack W.P. Hayes, Jane C. Edwards, Rebecca K. McLean, Veronica Martini, Miriam Pedrera, Nazia Thakur, Carina Conceicao, Isabelle Dietrich, Holly Shelton, Anna Ludi, Ginette Wilsden, Clare Browning, Adrian K. ZagrajekDagmara Bialy, Sushant Bhat, Phoebe Stevenson-Leggett, Philippa Hollinghurst, Matthew Tully, Katy Moffat, Chris Chiu, Ryan Waters, Ashley Gray, Mehreen Azhar, Valerie Mioulet, Joseph Newman, Amin S. Asfor, Alison Burman, Sylvia Crossley, John A. Hammond, Elma Tchilian, Bryan Charleston, Dalan Bailey, Tobias J. Tuthill, Simon P. Graham, Helen M.E. Duyvesteyn, Tomas Malinauskas, Jiandong Huo, Julia A. Tree, Karen R. Buttigieg, Raymond J. Owens, Miles W. Carroll, Rodney S. Daniels, John W. McCauley, David I. Stuart, Kuan Ying A. Huang, Mark Howarth^*, Alain R. Townsend^*

^*此作品的通信作者

醫學系

研究成果: 期刊稿件 › 文章 › 同行評審

218 引文斯高帕斯（Scopus）

摘要

There is need for effective and affordable vaccines against SARS-CoV-2 to tackle the ongoing pandemic. In this study, we describe a protein nanoparticle vaccine against SARS-CoV-2. The vaccine is based on the display of coronavirus spike glycoprotein receptor-binding domain (RBD) on a synthetic virus-like particle (VLP) platform, SpyCatcher003-mi3, using SpyTag/SpyCatcher technology. Low doses of RBD-SpyVLP in a prime-boost regimen induce a strong neutralising antibody response in mice and pigs that is superior to convalescent human sera. We evaluate antibody quality using ACE2 blocking and neutralisation of cell infection by pseudovirus or wild-type SARS-CoV-2. Using competition assays with a monoclonal antibody panel, we show that RBD-SpyVLP induces a polyclonal antibody response that recognises key epitopes on the RBD, reducing the likelihood of selecting neutralisation-escape mutants. Moreover, RBD-SpyVLP is thermostable and can be lyophilised without losing immunogenicity, to facilitate global distribution and reduce cold-chain dependence. The data suggests that RBD-SpyVLP provides strong potential to address clinical and logistic challenges of the COVID-19 pandemic.

原文	英語
文章編號	542
期刊	Nature Communications
卷	12
發行號	1
DOIs	https://doi.org/10.1038/s41467-020-20654-7
出版狀態	已出版 - 12 2021

文獻附註

Publisher Copyright:
© 2021, The Author(s).

UN SDG

此研究成果有助於以下永續發展目標

存取文件

10.1038/s41467-020-20654-7

其它文件與鏈接

Link to publication in Scopus

引用此

Tan, T. K., Rijal, P., Rahikainen, R., Keeble, A. H., Schimanski, L., Hussain, S., Harvey, R., Hayes, J. W. P., Edwards, J. C., McLean, R. K., Martini, V., Pedrera, M., Thakur, N., Conceicao, C., Dietrich, I., Shelton, H., Ludi, A., Wilsden, G., Browning, C., ... Townsend, A. R. (2021). A COVID-19 vaccine candidate using SpyCatcher multimerization of the SARS-CoV-2 spike protein receptor-binding domain induces potent neutralising antibody responses. Nature Communications, 12(1), 文章 542. https://doi.org/10.1038/s41467-020-20654-7

@article{8aab9387f76f4c449a80ed758152e36a,

title = "A COVID-19 vaccine candidate using SpyCatcher multimerization of the SARS-CoV-2 spike protein receptor-binding domain induces potent neutralising antibody responses",

abstract = "There is need for effective and affordable vaccines against SARS-CoV-2 to tackle the ongoing pandemic. In this study, we describe a protein nanoparticle vaccine against SARS-CoV-2. The vaccine is based on the display of coronavirus spike glycoprotein receptor-binding domain (RBD) on a synthetic virus-like particle (VLP) platform, SpyCatcher003-mi3, using SpyTag/SpyCatcher technology. Low doses of RBD-SpyVLP in a prime-boost regimen induce a strong neutralising antibody response in mice and pigs that is superior to convalescent human sera. We evaluate antibody quality using ACE2 blocking and neutralisation of cell infection by pseudovirus or wild-type SARS-CoV-2. Using competition assays with a monoclonal antibody panel, we show that RBD-SpyVLP induces a polyclonal antibody response that recognises key epitopes on the RBD, reducing the likelihood of selecting neutralisation-escape mutants. Moreover, RBD-SpyVLP is thermostable and can be lyophilised without losing immunogenicity, to facilitate global distribution and reduce cold-chain dependence. The data suggests that RBD-SpyVLP provides strong potential to address clinical and logistic challenges of the COVID-19 pandemic.",

author = "Tan, \{Tiong Kit\} and Pramila Rijal and Rolle Rahikainen and Keeble, \{Anthony H.\} and Lisa Schimanski and Saira Hussain and Ruth Harvey and Hayes, \{Jack W.P.\} and Edwards, \{Jane C.\} and McLean, \{Rebecca K.\} and Veronica Martini and Miriam Pedrera and Nazia Thakur and Carina Conceicao and Isabelle Dietrich and Holly Shelton and Anna Ludi and Ginette Wilsden and Clare Browning and Zagrajek, \{Adrian K.\} and Dagmara Bialy and Sushant Bhat and Phoebe Stevenson-Leggett and Philippa Hollinghurst and Matthew Tully and Katy Moffat and Chris Chiu and Ryan Waters and Ashley Gray and Mehreen Azhar and Valerie Mioulet and Joseph Newman and Asfor, \{Amin S.\} and Alison Burman and Sylvia Crossley and Hammond, \{John A.\} and Elma Tchilian and Bryan Charleston and Dalan Bailey and Tuthill, \{Tobias J.\} and Graham, \{Simon P.\} and Duyvesteyn, \{Helen M.E.\} and Tomas Malinauskas and Jiandong Huo and Tree, \{Julia A.\} and Buttigieg, \{Karen R.\} and Owens, \{Raymond J.\} and Carroll, \{Miles W.\} and Daniels, \{Rodney S.\} and McCauley, \{John W.\} and Stuart, \{David I.\} and Huang, \{Kuan Ying A.\} and Mark Howarth and Townsend, \{Alain R.\}",

note = "Publisher Copyright: {\textcopyright} 2021, The Author(s).",

year = "2021",

month = dec,

doi = "10.1038/s41467-020-20654-7",

language = "英语",

volume = "12",

journal = "Nature Communications",

issn = "2041-1723",

publisher = "Nature Research",

number = "1",

}

Tan, TK, Rijal, P, Rahikainen, R, Keeble, AH, Schimanski, L, Hussain, S, Harvey, R, Hayes, JWP, Edwards, JC, McLean, RK, Martini, V, Pedrera, M, Thakur, N, Conceicao, C, Dietrich, I, Shelton, H, Ludi, A, Wilsden, G, Browning, C, Zagrajek, AK, Bialy, D, Bhat, S, Stevenson-Leggett, P, Hollinghurst, P, Tully, M, Moffat, K, Chiu, C, Waters, R, Gray, A, Azhar, M, Mioulet, V, Newman, J, Asfor, AS, Burman, A, Crossley, S, Hammond, JA, Tchilian, E, Charleston, B, Bailey, D, Tuthill, TJ, Graham, SP, Duyvesteyn, HME, Malinauskas, T, Huo, J, Tree, JA, Buttigieg, KR, Owens, RJ, Carroll, MW, Daniels, RS, McCauley, JW, Stuart, DI, Huang, KYA, Howarth, M & Townsend, AR 2021, 'A COVID-19 vaccine candidate using SpyCatcher multimerization of the SARS-CoV-2 spike protein receptor-binding domain induces potent neutralising antibody responses', Nature Communications, 卷 12, 編號 1, 542. https://doi.org/10.1038/s41467-020-20654-7

TY - JOUR

T1 - A COVID-19 vaccine candidate using SpyCatcher multimerization of the SARS-CoV-2 spike protein receptor-binding domain induces potent neutralising antibody responses

AU - Tan, Tiong Kit

AU - Rijal, Pramila

AU - Rahikainen, Rolle

AU - Keeble, Anthony H.

AU - Schimanski, Lisa

AU - Hussain, Saira

AU - Harvey, Ruth

AU - Hayes, Jack W.P.

AU - Edwards, Jane C.

AU - McLean, Rebecca K.

AU - Martini, Veronica

AU - Pedrera, Miriam

AU - Thakur, Nazia

AU - Conceicao, Carina

AU - Dietrich, Isabelle

AU - Shelton, Holly

AU - Ludi, Anna

AU - Wilsden, Ginette

AU - Browning, Clare

AU - Zagrajek, Adrian K.

AU - Bialy, Dagmara

AU - Bhat, Sushant

AU - Stevenson-Leggett, Phoebe

AU - Hollinghurst, Philippa

AU - Tully, Matthew

AU - Moffat, Katy

AU - Chiu, Chris

AU - Waters, Ryan

AU - Gray, Ashley

AU - Azhar, Mehreen

AU - Mioulet, Valerie

AU - Newman, Joseph

AU - Asfor, Amin S.

AU - Burman, Alison

AU - Crossley, Sylvia

AU - Hammond, John A.

AU - Tchilian, Elma

AU - Charleston, Bryan

AU - Bailey, Dalan

AU - Tuthill, Tobias J.

AU - Graham, Simon P.

AU - Duyvesteyn, Helen M.E.

AU - Malinauskas, Tomas

AU - Huo, Jiandong

AU - Tree, Julia A.

AU - Buttigieg, Karen R.

AU - Owens, Raymond J.

AU - Carroll, Miles W.

AU - Daniels, Rodney S.

AU - McCauley, John W.

AU - Stuart, David I.

AU - Huang, Kuan Ying A.

AU - Howarth, Mark

AU - Townsend, Alain R.

PY - 2021/12

Y1 - 2021/12

N2 - There is need for effective and affordable vaccines against SARS-CoV-2 to tackle the ongoing pandemic. In this study, we describe a protein nanoparticle vaccine against SARS-CoV-2. The vaccine is based on the display of coronavirus spike glycoprotein receptor-binding domain (RBD) on a synthetic virus-like particle (VLP) platform, SpyCatcher003-mi3, using SpyTag/SpyCatcher technology. Low doses of RBD-SpyVLP in a prime-boost regimen induce a strong neutralising antibody response in mice and pigs that is superior to convalescent human sera. We evaluate antibody quality using ACE2 blocking and neutralisation of cell infection by pseudovirus or wild-type SARS-CoV-2. Using competition assays with a monoclonal antibody panel, we show that RBD-SpyVLP induces a polyclonal antibody response that recognises key epitopes on the RBD, reducing the likelihood of selecting neutralisation-escape mutants. Moreover, RBD-SpyVLP is thermostable and can be lyophilised without losing immunogenicity, to facilitate global distribution and reduce cold-chain dependence. The data suggests that RBD-SpyVLP provides strong potential to address clinical and logistic challenges of the COVID-19 pandemic.

AB - There is need for effective and affordable vaccines against SARS-CoV-2 to tackle the ongoing pandemic. In this study, we describe a protein nanoparticle vaccine against SARS-CoV-2. The vaccine is based on the display of coronavirus spike glycoprotein receptor-binding domain (RBD) on a synthetic virus-like particle (VLP) platform, SpyCatcher003-mi3, using SpyTag/SpyCatcher technology. Low doses of RBD-SpyVLP in a prime-boost regimen induce a strong neutralising antibody response in mice and pigs that is superior to convalescent human sera. We evaluate antibody quality using ACE2 blocking and neutralisation of cell infection by pseudovirus or wild-type SARS-CoV-2. Using competition assays with a monoclonal antibody panel, we show that RBD-SpyVLP induces a polyclonal antibody response that recognises key epitopes on the RBD, reducing the likelihood of selecting neutralisation-escape mutants. Moreover, RBD-SpyVLP is thermostable and can be lyophilised without losing immunogenicity, to facilitate global distribution and reduce cold-chain dependence. The data suggests that RBD-SpyVLP provides strong potential to address clinical and logistic challenges of the COVID-19 pandemic.

UR - https://www.scopus.com/pages/publications/85099910641

U2 - 10.1038/s41467-020-20654-7

DO - 10.1038/s41467-020-20654-7

M3 - 文章

C2 - 33483491

AN - SCOPUS:85099910641

SN - 2041-1723

VL - 12

JO - Nature Communications

JF - Nature Communications

IS - 1

M1 - 542

ER -

A COVID-19 vaccine candidate using SpyCatcher multimerization of the SARS-CoV-2 spike protein receptor-binding domain induces potent neutralising antibody responses

摘要

文獻附註

UN SDG

存取文件

其它文件與鏈接

指紋

引用此