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SARS‐CoV‐2 Spike Stem Protein Nanoparticles Elicited Broad ADCC and Robust Neutralization against Variants in Mice

Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) has caused the global pandemic. The virus is rapidly evolving, characterized by the emergence of several major variants. Stable prefusion spike protein (Pre) is the immunogen in current vaccines but is limited in protecting against differe...

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Autores principales: Ma, Yao, Wang, Ye, Dong, Chunhong, Gonzalez, Gilbert X., Zhu, Wandi, Kim, Joo, Wei, Lai, Kang, Sang‐Moo, Wang, Bao‐Zhong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9233155/
https://www.ncbi.nlm.nih.gov/pubmed/35607768
http://dx.doi.org/10.1002/smll.202200836
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author Ma, Yao
Wang, Ye
Dong, Chunhong
Gonzalez, Gilbert X.
Zhu, Wandi
Kim, Joo
Wei, Lai
Kang, Sang‐Moo
Wang, Bao‐Zhong
author_facet Ma, Yao
Wang, Ye
Dong, Chunhong
Gonzalez, Gilbert X.
Zhu, Wandi
Kim, Joo
Wei, Lai
Kang, Sang‐Moo
Wang, Bao‐Zhong
author_sort Ma, Yao
collection PubMed
description Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) has caused the global pandemic. The virus is rapidly evolving, characterized by the emergence of several major variants. Stable prefusion spike protein (Pre) is the immunogen in current vaccines but is limited in protecting against different variants. Here, the immune responses induced by the relatively conserved stem subunit (S2) of spike protein versus Pre are investigated. Pre generates the most robust neutralization responses against SARS‐CoV‐2 variants in vesicular stomatitis virus pseudovirus‐based assessment but elicits less antibody‐dependent cellular cytotoxicity (ADCC) activity than S2. By contrast, S2 induces the most balanced immunoglobulin G (IgG) antibodies with potent and broad ADCC activity although produces weaker neutralization. The immunogenicity of S2 and Pre improves by incorporating the two proteins into double‐layered protein nanoparticles. The resulting protein nanoparticles Pre/S2 elicit higher neutralizing antibodies than Pre alone, and stronger ADCC than S2 alone. Moreover, nanoparticles produce more potent and balanced serum IgG antibodies than the corresponding soluble protein mixture, and the immune responses are sustained for at least four months after the immunization. Thus, the double‐layered protein nanoparticles have the potential to be developed into broader SARS‐CoV‐2 vaccines with excellent safety profiles.
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spelling pubmed-92331552022-08-04 SARS‐CoV‐2 Spike Stem Protein Nanoparticles Elicited Broad ADCC and Robust Neutralization against Variants in Mice Ma, Yao Wang, Ye Dong, Chunhong Gonzalez, Gilbert X. Zhu, Wandi Kim, Joo Wei, Lai Kang, Sang‐Moo Wang, Bao‐Zhong Small Research Articles Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) has caused the global pandemic. The virus is rapidly evolving, characterized by the emergence of several major variants. Stable prefusion spike protein (Pre) is the immunogen in current vaccines but is limited in protecting against different variants. Here, the immune responses induced by the relatively conserved stem subunit (S2) of spike protein versus Pre are investigated. Pre generates the most robust neutralization responses against SARS‐CoV‐2 variants in vesicular stomatitis virus pseudovirus‐based assessment but elicits less antibody‐dependent cellular cytotoxicity (ADCC) activity than S2. By contrast, S2 induces the most balanced immunoglobulin G (IgG) antibodies with potent and broad ADCC activity although produces weaker neutralization. The immunogenicity of S2 and Pre improves by incorporating the two proteins into double‐layered protein nanoparticles. The resulting protein nanoparticles Pre/S2 elicit higher neutralizing antibodies than Pre alone, and stronger ADCC than S2 alone. Moreover, nanoparticles produce more potent and balanced serum IgG antibodies than the corresponding soluble protein mixture, and the immune responses are sustained for at least four months after the immunization. Thus, the double‐layered protein nanoparticles have the potential to be developed into broader SARS‐CoV‐2 vaccines with excellent safety profiles. John Wiley and Sons Inc. 2022-05-23 2022-06-23 /pmc/articles/PMC9233155/ /pubmed/35607768 http://dx.doi.org/10.1002/smll.202200836 Text en © 2022 Wiley‐VCH GmbH This article is being made freely available through PubMed Central as part of the COVID-19 public health emergency response. It can be used for unrestricted research re-use and analysis in any form or by any means with acknowledgement of the original source, for the duration of the public health emergency.
spellingShingle Research Articles
Ma, Yao
Wang, Ye
Dong, Chunhong
Gonzalez, Gilbert X.
Zhu, Wandi
Kim, Joo
Wei, Lai
Kang, Sang‐Moo
Wang, Bao‐Zhong
SARS‐CoV‐2 Spike Stem Protein Nanoparticles Elicited Broad ADCC and Robust Neutralization against Variants in Mice
title SARS‐CoV‐2 Spike Stem Protein Nanoparticles Elicited Broad ADCC and Robust Neutralization against Variants in Mice
title_full SARS‐CoV‐2 Spike Stem Protein Nanoparticles Elicited Broad ADCC and Robust Neutralization against Variants in Mice
title_fullStr SARS‐CoV‐2 Spike Stem Protein Nanoparticles Elicited Broad ADCC and Robust Neutralization against Variants in Mice
title_full_unstemmed SARS‐CoV‐2 Spike Stem Protein Nanoparticles Elicited Broad ADCC and Robust Neutralization against Variants in Mice
title_short SARS‐CoV‐2 Spike Stem Protein Nanoparticles Elicited Broad ADCC and Robust Neutralization against Variants in Mice
title_sort sars‐cov‐2 spike stem protein nanoparticles elicited broad adcc and robust neutralization against variants in mice
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9233155/
https://www.ncbi.nlm.nih.gov/pubmed/35607768
http://dx.doi.org/10.1002/smll.202200836
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