Ad26.COV2.S protects Syrian hamsters against G614 spike variant SARS-CoV-2 and does not enhance respiratory disease

Abstract Previously we have shown that a single dose of recombinant adenovirus serotype 26 (Ad26) vaccine expressing a prefusion stabilized SARS-CoV-2 spike antigen (Ad26.COV2.S) is immunogenic and provides protection in Syrian hamster and non-human primate SARS-CoV-2 infection models. Here, we inve...

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Autores principales:	Joan E. M. van der Lubbe, Sietske K. Rosendahl Huber, Aneesh Vijayan, Liesbeth Dekking, Ella van Huizen, Jessica Vreugdenhil, Ying Choi, Miranda R. M. Baert, Karin Feddes-de Boer, Ana Izquierdo Gil, Marjolein van Heerden, Tim J. Dalebout, Sebenzile K. Myeni, Marjolein Kikkert, Eric J. Snijder, Leon de Waal, Koert J. Stittelaar, Jeroen T. B. M. Tolboom, Jan Serroyen, Leacky Muchene, Leslie van der Fits, Lucy Rutten, Johannes P. M. Langedijk, Dan H. Barouch, Hanneke Schuitemaker, Roland C. Zahn, Frank Wegmann
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Immunologic diseases. Allergy RC581-607 Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/fc2cb2bea71d44b4a49590c0dc2b55f2
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spelling	oai:doaj.org-article:fc2cb2bea71d44b4a49590c0dc2b55f22021-12-02T16:30:46ZAd26.COV2.S protects Syrian hamsters against G614 spike variant SARS-CoV-2 and does not enhance respiratory disease10.1038/s41541-021-00301-y2059-0105https://doaj.org/article/fc2cb2bea71d44b4a49590c0dc2b55f22021-03-01T00:00:00Zhttps://doi.org/10.1038/s41541-021-00301-yhttps://doaj.org/toc/2059-0105Abstract Previously we have shown that a single dose of recombinant adenovirus serotype 26 (Ad26) vaccine expressing a prefusion stabilized SARS-CoV-2 spike antigen (Ad26.COV2.S) is immunogenic and provides protection in Syrian hamster and non-human primate SARS-CoV-2 infection models. Here, we investigated the immunogenicity, protective efficacy, and potential for vaccine-associated enhanced respiratory disease (VAERD) mediated by Ad26.COV2.S in a moderate disease Syrian hamster challenge model, using the currently most prevalent G614 spike SARS-CoV-2 variant. Vaccine doses of 1 × 109 and 1 × 1010 VP elicited substantial neutralizing antibodies titers and completely protected over 80% of SARS-CoV-2 inoculated Syrian hamsters from lung infection and pneumonia but not upper respiratory tract infection. A second vaccine dose further increased neutralizing antibody titers that was associated with decreased infectious viral load in the upper respiratory tract after SARS-CoV-2 challenge. Suboptimal non-protective immune responses elicited by low-dose A26.COV2.S vaccination did not exacerbate respiratory disease in SARS-CoV-2-inoculated Syrian hamsters with breakthrough infection. In addition, dosing down the vaccine allowed to establish that binding and neutralizing antibody titers correlate with lower respiratory tract protection probability. Overall, these preclinical data confirm efficacy of a one-dose vaccine regimen with Ad26.COV2.S in this G614 spike SARS-CoV-2 virus variant Syrian hamster model, show the added benefit of a second vaccine dose, and demonstrate that there are no signs of VAERD under conditions of suboptimal immunity.Joan E. M. van der LubbeSietske K. Rosendahl HuberAneesh VijayanLiesbeth DekkingElla van HuizenJessica VreugdenhilYing ChoiMiranda R. M. BaertKarin Feddes-de BoerAna Izquierdo GilMarjolein van HeerdenTim J. DaleboutSebenzile K. MyeniMarjolein KikkertEric J. SnijderLeon de WaalKoert J. StittelaarJeroen T. B. M. TolboomJan SerroyenLeacky MucheneLeslie van der FitsLucy RuttenJohannes P. M. LangedijkDan H. BarouchHanneke SchuitemakerRoland C. ZahnFrank WegmannNature PortfolioarticleImmunologic diseases. AllergyRC581-607Neoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENnpj Vaccines, Vol 6, Iss 1, Pp 1-12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Immunologic diseases. Allergy RC581-607 Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	Immunologic diseases. Allergy RC581-607 Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Joan E. M. van der Lubbe Sietske K. Rosendahl Huber Aneesh Vijayan Liesbeth Dekking Ella van Huizen Jessica Vreugdenhil Ying Choi Miranda R. M. Baert Karin Feddes-de Boer Ana Izquierdo Gil Marjolein van Heerden Tim J. Dalebout Sebenzile K. Myeni Marjolein Kikkert Eric J. Snijder Leon de Waal Koert J. Stittelaar Jeroen T. B. M. Tolboom Jan Serroyen Leacky Muchene Leslie van der Fits Lucy Rutten Johannes P. M. Langedijk Dan H. Barouch Hanneke Schuitemaker Roland C. Zahn Frank Wegmann Ad26.COV2.S protects Syrian hamsters against G614 spike variant SARS-CoV-2 and does not enhance respiratory disease
description	Abstract Previously we have shown that a single dose of recombinant adenovirus serotype 26 (Ad26) vaccine expressing a prefusion stabilized SARS-CoV-2 spike antigen (Ad26.COV2.S) is immunogenic and provides protection in Syrian hamster and non-human primate SARS-CoV-2 infection models. Here, we investigated the immunogenicity, protective efficacy, and potential for vaccine-associated enhanced respiratory disease (VAERD) mediated by Ad26.COV2.S in a moderate disease Syrian hamster challenge model, using the currently most prevalent G614 spike SARS-CoV-2 variant. Vaccine doses of 1 × 109 and 1 × 1010 VP elicited substantial neutralizing antibodies titers and completely protected over 80% of SARS-CoV-2 inoculated Syrian hamsters from lung infection and pneumonia but not upper respiratory tract infection. A second vaccine dose further increased neutralizing antibody titers that was associated with decreased infectious viral load in the upper respiratory tract after SARS-CoV-2 challenge. Suboptimal non-protective immune responses elicited by low-dose A26.COV2.S vaccination did not exacerbate respiratory disease in SARS-CoV-2-inoculated Syrian hamsters with breakthrough infection. In addition, dosing down the vaccine allowed to establish that binding and neutralizing antibody titers correlate with lower respiratory tract protection probability. Overall, these preclinical data confirm efficacy of a one-dose vaccine regimen with Ad26.COV2.S in this G614 spike SARS-CoV-2 virus variant Syrian hamster model, show the added benefit of a second vaccine dose, and demonstrate that there are no signs of VAERD under conditions of suboptimal immunity.
format	article
author	Joan E. M. van der Lubbe Sietske K. Rosendahl Huber Aneesh Vijayan Liesbeth Dekking Ella van Huizen Jessica Vreugdenhil Ying Choi Miranda R. M. Baert Karin Feddes-de Boer Ana Izquierdo Gil Marjolein van Heerden Tim J. Dalebout Sebenzile K. Myeni Marjolein Kikkert Eric J. Snijder Leon de Waal Koert J. Stittelaar Jeroen T. B. M. Tolboom Jan Serroyen Leacky Muchene Leslie van der Fits Lucy Rutten Johannes P. M. Langedijk Dan H. Barouch Hanneke Schuitemaker Roland C. Zahn Frank Wegmann
author_facet	Joan E. M. van der Lubbe Sietske K. Rosendahl Huber Aneesh Vijayan Liesbeth Dekking Ella van Huizen Jessica Vreugdenhil Ying Choi Miranda R. M. Baert Karin Feddes-de Boer Ana Izquierdo Gil Marjolein van Heerden Tim J. Dalebout Sebenzile K. Myeni Marjolein Kikkert Eric J. Snijder Leon de Waal Koert J. Stittelaar Jeroen T. B. M. Tolboom Jan Serroyen Leacky Muchene Leslie van der Fits Lucy Rutten Johannes P. M. Langedijk Dan H. Barouch Hanneke Schuitemaker Roland C. Zahn Frank Wegmann
author_sort	Joan E. M. van der Lubbe
title	Ad26.COV2.S protects Syrian hamsters against G614 spike variant SARS-CoV-2 and does not enhance respiratory disease
title_short	Ad26.COV2.S protects Syrian hamsters against G614 spike variant SARS-CoV-2 and does not enhance respiratory disease
title_full	Ad26.COV2.S protects Syrian hamsters against G614 spike variant SARS-CoV-2 and does not enhance respiratory disease
title_fullStr	Ad26.COV2.S protects Syrian hamsters against G614 spike variant SARS-CoV-2 and does not enhance respiratory disease
title_full_unstemmed	Ad26.COV2.S protects Syrian hamsters against G614 spike variant SARS-CoV-2 and does not enhance respiratory disease
title_sort	ad26.cov2.s protects syrian hamsters against g614 spike variant sars-cov-2 and does not enhance respiratory disease
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/fc2cb2bea71d44b4a49590c0dc2b55f2
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Ad26.COV2.S protects Syrian hamsters against G614 spike variant SARS-CoV-2 and does not enhance respiratory disease

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