A class II MHC-targeted vaccine elicits immunity against SARS-CoV-2 and its variants

Novalia Pishesha; Thibault J Harmand; Paul W Rothlauf; Patrique Praest; Ryan K Alexander; Renate van den Doel; Mariel J Liebeskind; Maria A Vakaki; Nicholas McCaul; Charlotte Wijne; Elisha Verhaar; William Pinney; Hailey Heston; Louis-Marie Bloyet; Marjorie Cornejo Pontelli; Ma Xenia G Ilagan; Robert Jan Lebbink; William J Buchser; Emmanuel J H J Wiertz; Sean P J Whelan; Hidde L Ploegh

doi:10.1073/pnas.2116147118

A class II MHC-targeted vaccine elicits immunity against SARS-CoV-2 and its variants

Novalia Pishesha, Thibault J Harmand, Paul W Rothlauf, Patrique Praest, Ryan K Alexander, Renate van den Doel, Mariel J Liebeskind, Maria A Vakaki, Nicholas McCaul, Charlotte Wijne, Elisha Verhaar, William Pinney, Hailey Heston, Louis-Marie Bloyet, Marjorie Cornejo Pontelli, Ma Xenia G Ilagan, Robert Jan Lebbink, William J Buchser, Emmanuel J H J Wiertz, Sean P J WhelanHidde L Ploegh

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

4 Downloads (Pure)

Abstract

The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in over 100 million infections and millions of deaths. Effective vaccines remain the best hope of curtailing SARS-CoV-2 transmission, morbidity, and mortality. The vaccines in current use require cold storage and sophisticated manufacturing capacity, which complicates their distribution, especially in less developed countries. We report the development of a candidate SARS-CoV-2 vaccine that is purely protein based and directly targets antigen-presenting cells. It consists of the SARS-CoV-2 Spike receptor-binding domain (SpikeRBD) fused to an alpaca-derived nanobody that recognizes class II major histocompatibility complex antigens (VHHMHCII). This vaccine elicits robust humoral and cellular immunity against SARS-CoV-2 and its variants. Both young and aged mice immunized with two doses of VHHMHCII-SpikeRBD elicit high-titer binding and neutralizing antibodies. Immunization also induces strong cellular immunity, including a robust CD8 T cell response. VHHMHCII-SpikeRBD is stable for at least 7 d at room temperature and can be lyophilized without loss of efficacy.

Original language	English
Article number	e2116147118
Pages (from-to)	1-10
Journal	Proceedings of the National Academy of Sciences of the United States of America
Volume	118
Issue number	44
DOIs	https://doi.org/10.1073/pnas.2116147118
Publication status	Published - 2 Nov 2021

Keywords

Amino Acid Sequence
Animals
Antibodies, Neutralizing/biosynthesis
Antibodies, Viral/biosynthesis
Antigen-Presenting Cells/immunology
CD8-Positive T-Lymphocytes/immunology
COVID-19 Vaccines/administration & dosage
COVID-19/epidemiology
Camelids, New World/immunology
Female
Histocompatibility Antigens Class II/immunology
Humans
Immunity, Cellular
Immunity, Humoral
Immunization, Secondary
Mice
Mice, Inbred BALB C
Mice, Inbred C57BL
Mice, Transgenic
Pandemics/prevention & control
Recombinant Fusion Proteins/administration & dosage
SARS-CoV-2/genetics
Single-Domain Antibodies/administration & dosage
Spike Glycoprotein, Coronavirus/administration & dosage
COVID-19
Nanobody
Vaccine

Access to Document

10.1073/pnas.2116147118Licence: CC BY

e2116147118.fullFinal published version, 1.12 MBLicence: CC BY

Cite this

Pishesha, N., Harmand, T. J., Rothlauf, P. W., Praest, P., Alexander, R. K., van den Doel, R., Liebeskind, M. J., Vakaki, M. A., McCaul, N., Wijne, C., Verhaar, E., Pinney, W., Heston, H., Bloyet, L.-M., Pontelli, M. C., Ilagan, M. X. G., Jan Lebbink, R., Buchser, W. J., Wiertz, E. J. H. J., ... Ploegh, H. L. (2021). A class II MHC-targeted vaccine elicits immunity against SARS-CoV-2 and its variants. Proceedings of the National Academy of Sciences of the United States of America, 118(44), 1-10. Article e2116147118. https://doi.org/10.1073/pnas.2116147118

@article{a11561f2353e4d09a0839b80fa67e79f,

title = "A class II MHC-targeted vaccine elicits immunity against SARS-CoV-2 and its variants",

abstract = "The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in over 100 million infections and millions of deaths. Effective vaccines remain the best hope of curtailing SARS-CoV-2 transmission, morbidity, and mortality. The vaccines in current use require cold storage and sophisticated manufacturing capacity, which complicates their distribution, especially in less developed countries. We report the development of a candidate SARS-CoV-2 vaccine that is purely protein based and directly targets antigen-presenting cells. It consists of the SARS-CoV-2 Spike receptor-binding domain (SpikeRBD) fused to an alpaca-derived nanobody that recognizes class II major histocompatibility complex antigens (VHHMHCII). This vaccine elicits robust humoral and cellular immunity against SARS-CoV-2 and its variants. Both young and aged mice immunized with two doses of VHHMHCII-SpikeRBD elicit high-titer binding and neutralizing antibodies. Immunization also induces strong cellular immunity, including a robust CD8 T cell response. VHHMHCII-SpikeRBD is stable for at least 7 d at room temperature and can be lyophilized without loss of efficacy.",

keywords = "Amino Acid Sequence, Animals, Antibodies, Neutralizing/biosynthesis, Antibodies, Viral/biosynthesis, Antigen-Presenting Cells/immunology, CD8-Positive T-Lymphocytes/immunology, COVID-19 Vaccines/administration & dosage, COVID-19/epidemiology, Camelids, New World/immunology, Female, Histocompatibility Antigens Class II/immunology, Humans, Immunity, Cellular, Immunity, Humoral, Immunization, Secondary, Mice, Mice, Inbred BALB C, Mice, Inbred C57BL, Mice, Transgenic, Pandemics/prevention & control, Recombinant Fusion Proteins/administration & dosage, SARS-CoV-2/genetics, Single-Domain Antibodies/administration & dosage, Spike Glycoprotein, Coronavirus/administration & dosage, COVID-19, Nanobody, Vaccine",

author = "Novalia Pishesha and Harmand, {Thibault J} and Rothlauf, {Paul W} and Patrique Praest and Alexander, {Ryan K} and {van den Doel}, Renate and Liebeskind, {Mariel J} and Vakaki, {Maria A} and Nicholas McCaul and Charlotte Wijne and Elisha Verhaar and William Pinney and Hailey Heston and Louis-Marie Bloyet and Pontelli, {Marjorie Cornejo} and Ilagan, {Ma Xenia G} and {Jan Lebbink}, Robert and Buchser, {William J} and Wiertz, {Emmanuel J H J} and Whelan, {Sean P J} and Ploegh, {Hidde L}",

note = "Funding Information: ACKNOWLEDGMENTS. This study was supported by a Junior Fellowship from Harvard Society of Fellows (to N.P.), a Postdoc Mobility fellowship from the Swiss National Science Foundation, Grant P400P2_183857 (to T.J.H.), the NIH Director{\textquoteright}s Pioneer Award, Grant 1DP1AI150593-01 (to H.L.P.), and the European Virus Archive goes global project, which has received funding from the European Union{\textquoteright}s Horizon 2020 research and innovation program under Grant Agreement 653316. Publisher Copyright: {\textcopyright} 2021 National Academy of Sciences. All rights reserved.",

year = "2021",

month = nov,

day = "2",

doi = "10.1073/pnas.2116147118",

language = "English",

volume = "118",

pages = "1--10",

journal = "Proceedings of the National Academy of Sciences of the United States of America",

issn = "0027-8424",

publisher = "National Academy of Sciences",

number = "44",

}

Pishesha, N, Harmand, TJ, Rothlauf, PW, Praest, P, Alexander, RK, van den Doel, R, Liebeskind, MJ, Vakaki, MA, McCaul, N, Wijne, C, Verhaar, E, Pinney, W, Heston, H, Bloyet, L-M, Pontelli, MC, Ilagan, MXG, Jan Lebbink, R, Buchser, WJ, Wiertz, EJHJ, Whelan, SPJ & Ploegh, HL 2021, 'A class II MHC-targeted vaccine elicits immunity against SARS-CoV-2 and its variants', Proceedings of the National Academy of Sciences of the United States of America, vol. 118, no. 44, e2116147118, pp. 1-10. https://doi.org/10.1073/pnas.2116147118

TY - JOUR

T1 - A class II MHC-targeted vaccine elicits immunity against SARS-CoV-2 and its variants

AU - Pishesha, Novalia

AU - Harmand, Thibault J

AU - Rothlauf, Paul W

AU - Praest, Patrique

AU - Alexander, Ryan K

AU - van den Doel, Renate

AU - Liebeskind, Mariel J

AU - Vakaki, Maria A

AU - McCaul, Nicholas

AU - Wijne, Charlotte

AU - Verhaar, Elisha

AU - Pinney, William

AU - Heston, Hailey

AU - Bloyet, Louis-Marie

AU - Pontelli, Marjorie Cornejo

AU - Ilagan, Ma Xenia G

AU - Jan Lebbink, Robert

AU - Buchser, William J

AU - Wiertz, Emmanuel J H J

AU - Whelan, Sean P J

AU - Ploegh, Hidde L

N1 - Funding Information: ACKNOWLEDGMENTS. This study was supported by a Junior Fellowship from Harvard Society of Fellows (to N.P.), a Postdoc Mobility fellowship from the Swiss National Science Foundation, Grant P400P2_183857 (to T.J.H.), the NIH Director’s Pioneer Award, Grant 1DP1AI150593-01 (to H.L.P.), and the European Virus Archive goes global project, which has received funding from the European Union’s Horizon 2020 research and innovation program under Grant Agreement 653316. Publisher Copyright: © 2021 National Academy of Sciences. All rights reserved.

PY - 2021/11/2

Y1 - 2021/11/2

N2 - The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in over 100 million infections and millions of deaths. Effective vaccines remain the best hope of curtailing SARS-CoV-2 transmission, morbidity, and mortality. The vaccines in current use require cold storage and sophisticated manufacturing capacity, which complicates their distribution, especially in less developed countries. We report the development of a candidate SARS-CoV-2 vaccine that is purely protein based and directly targets antigen-presenting cells. It consists of the SARS-CoV-2 Spike receptor-binding domain (SpikeRBD) fused to an alpaca-derived nanobody that recognizes class II major histocompatibility complex antigens (VHHMHCII). This vaccine elicits robust humoral and cellular immunity against SARS-CoV-2 and its variants. Both young and aged mice immunized with two doses of VHHMHCII-SpikeRBD elicit high-titer binding and neutralizing antibodies. Immunization also induces strong cellular immunity, including a robust CD8 T cell response. VHHMHCII-SpikeRBD is stable for at least 7 d at room temperature and can be lyophilized without loss of efficacy.

AB - The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in over 100 million infections and millions of deaths. Effective vaccines remain the best hope of curtailing SARS-CoV-2 transmission, morbidity, and mortality. The vaccines in current use require cold storage and sophisticated manufacturing capacity, which complicates their distribution, especially in less developed countries. We report the development of a candidate SARS-CoV-2 vaccine that is purely protein based and directly targets antigen-presenting cells. It consists of the SARS-CoV-2 Spike receptor-binding domain (SpikeRBD) fused to an alpaca-derived nanobody that recognizes class II major histocompatibility complex antigens (VHHMHCII). This vaccine elicits robust humoral and cellular immunity against SARS-CoV-2 and its variants. Both young and aged mice immunized with two doses of VHHMHCII-SpikeRBD elicit high-titer binding and neutralizing antibodies. Immunization also induces strong cellular immunity, including a robust CD8 T cell response. VHHMHCII-SpikeRBD is stable for at least 7 d at room temperature and can be lyophilized without loss of efficacy.

KW - Amino Acid Sequence

KW - Animals

KW - Antibodies, Neutralizing/biosynthesis

KW - Antibodies, Viral/biosynthesis

KW - Antigen-Presenting Cells/immunology

KW - CD8-Positive T-Lymphocytes/immunology

KW - COVID-19 Vaccines/administration & dosage

KW - COVID-19/epidemiology

KW - Camelids, New World/immunology

KW - Female

KW - Histocompatibility Antigens Class II/immunology

KW - Humans

KW - Immunity, Cellular

KW - Immunity, Humoral

KW - Immunization, Secondary

KW - Mice

KW - Mice, Inbred BALB C

KW - Mice, Inbred C57BL

KW - Mice, Transgenic

KW - Pandemics/prevention & control

KW - Recombinant Fusion Proteins/administration & dosage

KW - SARS-CoV-2/genetics

KW - Single-Domain Antibodies/administration & dosage

KW - Spike Glycoprotein, Coronavirus/administration & dosage

KW - COVID-19

KW - Nanobody

KW - Vaccine

UR - http://www.scopus.com/inward/record.url?scp=85118213216&partnerID=8YFLogxK

U2 - 10.1073/pnas.2116147118

DO - 10.1073/pnas.2116147118

M3 - Article

C2 - 34654739

SN - 0027-8424

VL - 118

SP - 1

EP - 10

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

IS - 44

M1 - e2116147118

ER -

A class II MHC-targeted vaccine elicits immunity against SARS-CoV-2 and its variants

Abstract

Keywords

Access to Document

Other files and links

Fingerprint

Cite this