Live-attenuated vaccine sCPD9 elicits superior mucosal and systemic immunity to SARS-CoV-2 variants in hamsters

Geraldine Nouailles; Julia M. Adler; Peter Pennitz; Stefan Peidli; Luiz Gustavo Teixeira Alves; Morris Baumgardt; Judith Bushe; Anne Voss; Alina Langenhagen; Christine Langner; Ricardo Martin Vidal; Fabian Pott; Julia Kazmierski; Aileen Ebenig; Mona V. Lange; Michael D. Mühlebach; Cengiz Goekeri; Szandor Simmons; Na Xing; Azza Abdelgawad; Susanne Herwig; Günter Cichon; Daniela Niemeyer; Christian Drosten; Christine Goffinet; Markus Landthaler; Nils Blüthgen; Haibo Wu; Martin Witzenrath; Achim D. Gruber; Samantha D. Praktiknjo; Nikolaus Osterrieder; Emanuel Wyler; Dusan Kunec; Jakob Trimpert

doi:10.1038/s41564-023-01352-8

Live-attenuated vaccine sCPD9 elicits superior mucosal and systemic immunity to SARS-CoV-2 variants in hamsters

Geraldine Nouailles (Co-first Author), Julia M. Adler (Co-first Author), Peter Pennitz, Stefan Peidli, Luiz Gustavo Teixeira Alves, Morris Baumgardt, Judith Bushe, Anne Voss, Alina Langenhagen, Christine Langner, Ricardo Martin Vidal, Fabian Pott, Julia Kazmierski, Aileen Ebenig, Mona V. Lange, Michael D. Mühlebach, Cengiz Goekeri, Szandor Simmons, Na Xing, Azza AbdelgawadSusanne Herwig, Günter Cichon, Daniela Niemeyer, Christian Drosten, Christine Goffinet, Markus Landthaler, Nils Blüthgen, Haibo Wu, Martin Witzenrath, Achim D. Gruber, Samantha D. Praktiknjo, Nikolaus Osterrieder, Emanuel Wyler, Dusan Kunec, Jakob Trimpert^*

^*Corresponding author for this work

Research output: Journal Publications and Reviews › RGC 21 - Publication in refereed journal › peer-review

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Abstract

Vaccines play a critical role in combating the COVID-19 pandemic. Future control of the pandemic requires improved vaccines with high efficacy against newly emerging SARS-CoV-2 variants and the ability to reduce virus transmission. Here we compare immune responses and preclinical efficacy of the mRNA vaccine BNT162b2, the adenovirus-vectored spike vaccine Ad2-spike and the live-attenuated virus vaccine candidate sCPD9 in Syrian hamsters, using both homogeneous and heterologous vaccination regimens. Comparative vaccine efficacy was assessed by employing readouts from virus titrations to single-cell RNA sequencing. Our results show that sCPD9 vaccination elicited the most robust immunity, including rapid viral clearance, reduced tissue damage, fast differentiation of pre-plasmablasts, strong systemic and mucosal humoral responses, and rapid recall of memory T cells from lung tissue after challenge with heterologous SARS-CoV-2. Overall, our results demonstrate that live-attenuated vaccines offer advantages over currently available COVID-19 vaccines. © 2023, The Author(s).

Original language	English
Pages (from-to)	860-874
Journal	Nature Microbiology
Volume	8
Online published	3 Apr 2023
DOIs	https://doi.org/10.1038/s41564-023-01352-8
Publication status	Published - May 2023

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This full text is made available under CC-BY 4.0. https://creativecommons.org/licenses/by/4.0/

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Nouailles, G., Adler, J. M., Pennitz, P., Peidli, S., Teixeira Alves, L. G., Baumgardt, M., Bushe, J., Voss, A., Langenhagen, A., Langner, C., Martin Vidal, R., Pott, F., Kazmierski, J., Ebenig, A., Lange, M. V., Mühlebach, M. D., Goekeri, C., Simmons, S., Xing, N., ... Trimpert, J. (2023). Live-attenuated vaccine sCPD9 elicits superior mucosal and systemic immunity to SARS-CoV-2 variants in hamsters. Nature Microbiology, 8, 860-874. https://doi.org/10.1038/s41564-023-01352-8

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title = "Live-attenuated vaccine sCPD9 elicits superior mucosal and systemic immunity to SARS-CoV-2 variants in hamsters",

abstract = "Vaccines play a critical role in combating the COVID-19 pandemic. Future control of the pandemic requires improved vaccines with high efficacy against newly emerging SARS-CoV-2 variants and the ability to reduce virus transmission. Here we compare immune responses and preclinical efficacy of the mRNA vaccine BNT162b2, the adenovirus-vectored spike vaccine Ad2-spike and the live-attenuated virus vaccine candidate sCPD9 in Syrian hamsters, using both homogeneous and heterologous vaccination regimens. Comparative vaccine efficacy was assessed by employing readouts from virus titrations to single-cell RNA sequencing. Our results show that sCPD9 vaccination elicited the most robust immunity, including rapid viral clearance, reduced tissue damage, fast differentiation of pre-plasmablasts, strong systemic and mucosal humoral responses, and rapid recall of memory T cells from lung tissue after challenge with heterologous SARS-CoV-2. Overall, our results demonstrate that live-attenuated vaccines offer advantages over currently available COVID-19 vaccines. {\textcopyright} 2023, The Author(s).",

author = "Geraldine Nouailles and Adler, {Julia M.} and Peter Pennitz and Stefan Peidli and {Teixeira Alves}, {Luiz Gustavo} and Morris Baumgardt and Judith Bushe and Anne Voss and Alina Langenhagen and Christine Langner and {Martin Vidal}, Ricardo and Fabian Pott and Julia Kazmierski and Aileen Ebenig and Lange, {Mona V.} and M{\"u}hlebach, {Michael D.} and Cengiz Goekeri and Szandor Simmons and Na Xing and Azza Abdelgawad and Susanne Herwig and G{\"u}nter Cichon and Daniela Niemeyer and Christian Drosten and Christine Goffinet and Markus Landthaler and Nils Bl{\"u}thgen and Haibo Wu and Martin Witzenrath and Gruber, {Achim D.} and Praktiknjo, {Samantha D.} and Nikolaus Osterrieder and Emanuel Wyler and Dusan Kunec and Jakob Trimpert",

year = "2023",

month = may,

doi = "10.1038/s41564-023-01352-8",

language = "English",

volume = "8",

pages = "860--874",

journal = "Nature Microbiology",

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Nouailles, G, Adler, JM, Pennitz, P, Peidli, S, Teixeira Alves, LG, Baumgardt, M, Bushe, J, Voss, A, Langenhagen, A, Langner, C, Martin Vidal, R, Pott, F, Kazmierski, J, Ebenig, A, Lange, MV, Mühlebach, MD, Goekeri, C, Simmons, S, Xing, N, Abdelgawad, A, Herwig, S, Cichon, G, Niemeyer, D, Drosten, C, Goffinet, C, Landthaler, M, Blüthgen, N, Wu, H, Witzenrath, M, Gruber, AD, Praktiknjo, SD, Osterrieder, N, Wyler, E, Kunec, D & Trimpert, J 2023, 'Live-attenuated vaccine sCPD9 elicits superior mucosal and systemic immunity to SARS-CoV-2 variants in hamsters', Nature Microbiology, vol. 8, pp. 860-874. https://doi.org/10.1038/s41564-023-01352-8

Live-attenuated vaccine sCPD9 elicits superior mucosal and systemic immunity to SARS-CoV-2 variants in hamsters. / Nouailles, Geraldine (Co-first Author); Adler, Julia M. (Co-first Author); Pennitz, Peter et al.
In: Nature Microbiology, Vol. 8, 05.2023, p. 860-874.

Research output: Journal Publications and Reviews › RGC 21 - Publication in refereed journal › peer-review

TY - JOUR

T1 - Live-attenuated vaccine sCPD9 elicits superior mucosal and systemic immunity to SARS-CoV-2 variants in hamsters

AU - Nouailles, Geraldine

AU - Adler, Julia M.

AU - Pennitz, Peter

AU - Peidli, Stefan

AU - Teixeira Alves, Luiz Gustavo

AU - Baumgardt, Morris

AU - Bushe, Judith

AU - Voss, Anne

AU - Langenhagen, Alina

AU - Langner, Christine

AU - Martin Vidal, Ricardo

AU - Pott, Fabian

AU - Kazmierski, Julia

AU - Ebenig, Aileen

AU - Lange, Mona V.

AU - Mühlebach, Michael D.

AU - Goekeri, Cengiz

AU - Simmons, Szandor

AU - Xing, Na

AU - Abdelgawad, Azza

AU - Herwig, Susanne

AU - Cichon, Günter

AU - Niemeyer, Daniela

AU - Drosten, Christian

AU - Goffinet, Christine

AU - Landthaler, Markus

AU - Blüthgen, Nils

AU - Wu, Haibo

AU - Witzenrath, Martin

AU - Gruber, Achim D.

AU - Praktiknjo, Samantha D.

AU - Osterrieder, Nikolaus

AU - Wyler, Emanuel

AU - Kunec, Dusan

AU - Trimpert, Jakob

PY - 2023/5

Y1 - 2023/5

N2 - Vaccines play a critical role in combating the COVID-19 pandemic. Future control of the pandemic requires improved vaccines with high efficacy against newly emerging SARS-CoV-2 variants and the ability to reduce virus transmission. Here we compare immune responses and preclinical efficacy of the mRNA vaccine BNT162b2, the adenovirus-vectored spike vaccine Ad2-spike and the live-attenuated virus vaccine candidate sCPD9 in Syrian hamsters, using both homogeneous and heterologous vaccination regimens. Comparative vaccine efficacy was assessed by employing readouts from virus titrations to single-cell RNA sequencing. Our results show that sCPD9 vaccination elicited the most robust immunity, including rapid viral clearance, reduced tissue damage, fast differentiation of pre-plasmablasts, strong systemic and mucosal humoral responses, and rapid recall of memory T cells from lung tissue after challenge with heterologous SARS-CoV-2. Overall, our results demonstrate that live-attenuated vaccines offer advantages over currently available COVID-19 vaccines. © 2023, The Author(s).

AB - Vaccines play a critical role in combating the COVID-19 pandemic. Future control of the pandemic requires improved vaccines with high efficacy against newly emerging SARS-CoV-2 variants and the ability to reduce virus transmission. Here we compare immune responses and preclinical efficacy of the mRNA vaccine BNT162b2, the adenovirus-vectored spike vaccine Ad2-spike and the live-attenuated virus vaccine candidate sCPD9 in Syrian hamsters, using both homogeneous and heterologous vaccination regimens. Comparative vaccine efficacy was assessed by employing readouts from virus titrations to single-cell RNA sequencing. Our results show that sCPD9 vaccination elicited the most robust immunity, including rapid viral clearance, reduced tissue damage, fast differentiation of pre-plasmablasts, strong systemic and mucosal humoral responses, and rapid recall of memory T cells from lung tissue after challenge with heterologous SARS-CoV-2. Overall, our results demonstrate that live-attenuated vaccines offer advantages over currently available COVID-19 vaccines. © 2023, The Author(s).

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UR - https://www.scopus.com/record/pubmetrics.uri?eid=2-s2.0-85151465836&origin=recordpage

U2 - 10.1038/s41564-023-01352-8

DO - 10.1038/s41564-023-01352-8

M3 - RGC 21 - Publication in refereed journal

C2 - 37012419

SN - 2058-5276

VL - 8

SP - 860

EP - 874

JO - Nature Microbiology

JF - Nature Microbiology

ER -

Live-attenuated vaccine sCPD9 elicits superior mucosal and systemic immunity to SARS-CoV-2 variants in hamsters

Abstract

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