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Enhancing Anti-SARS-CoV-2 Neutralizing Immunity by Genetic Delivery of Enveloped Virus-like Particles Displaying SARS-CoV-2 Spikes
New vaccine delivery technologies, such as mRNA, have played a critical role in the rapid and efficient control of SARS-CoV-2, helping to end the COVID-19 pandemic. Enveloped virus-like particles (eVLPs) are often more immunogenic than protein subunit immunogens and could be an effective vaccine pla...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10537688/ https://www.ncbi.nlm.nih.gov/pubmed/37766115 http://dx.doi.org/10.3390/vaccines11091438 |
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author | Yang, Yongping Kong, Wing-Pui Liu, Cuiping Ruckwardt, Tracy J. Tsybovsky, Yaroslav Wang, Lingshu Wang, Shuishu Biner, Daniel W. Chen, Man Liu, Tracy Merriam, Jonah Olia, Adam S. Ou, Li Qiu, Qi Shi, Wei Stephens, Tyler Yang, Eun Sung Zhang, Baoshan Zhang, Yi Zhou, Qiong Rawi, Reda Koup, Richard A. Mascola, John R. Kwong, Peter D. |
author_facet | Yang, Yongping Kong, Wing-Pui Liu, Cuiping Ruckwardt, Tracy J. Tsybovsky, Yaroslav Wang, Lingshu Wang, Shuishu Biner, Daniel W. Chen, Man Liu, Tracy Merriam, Jonah Olia, Adam S. Ou, Li Qiu, Qi Shi, Wei Stephens, Tyler Yang, Eun Sung Zhang, Baoshan Zhang, Yi Zhou, Qiong Rawi, Reda Koup, Richard A. Mascola, John R. Kwong, Peter D. |
author_sort | Yang, Yongping |
collection | PubMed |
description | New vaccine delivery technologies, such as mRNA, have played a critical role in the rapid and efficient control of SARS-CoV-2, helping to end the COVID-19 pandemic. Enveloped virus-like particles (eVLPs) are often more immunogenic than protein subunit immunogens and could be an effective vaccine platform. Here, we investigated whether the genetic delivery of eVLPs could achieve strong immune responses in mice as previously reported with the immunization of in vitro purified eVLPs. We utilized Newcastle disease virus-like particles (NDVLPs) to display SARS-CoV-2 prefusion-stabilized spikes from the WA-1 or Beta variant (S-2P or S-2Pᵦ, respectively) and evaluated neutralizing murine immune responses achieved by a single-gene-transcript DNA construct for the WA-1 or Beta variant (which we named S-2P-NDVLP-1T and S-2Pᵦ-NDVLP-1T, respectively), by multiple-gene-transcript DNA constructs for the Beta variant (S-2Pᵦ-NDVLP-3T), and by a protein subunit–DNA construct for the WA-1 or Beta variant (S-2P-TM or S-2Pᵦ-TM, respectively). The genetic delivery of S-2P-NDVLP-1T or S-2Pᵦ-NDVLP-1T yielded modest neutralizing responses after a single immunization and high neutralizing responses after a second immunization, comparable to previously reported results in mice immunized with in vitro purified S-2P-NDVLPs. Notably, genetic delivery of S-2Pᵦ-NDVLP-3T yielded significantly higher neutralizing responses in mice after a second immunization than S-2Pᵦ-NDVLP-1T or S-2Pᵦ-TM. Genetic delivery also elicited high spike-specific T-cell responses. Collectively, these results indicate that genetic delivery can provide an effective means to immunize eVLPs and that a multiple-gene transcript eVLP platform may be especially efficacious and inform the design of improved vaccines. |
format | Online Article Text |
id | pubmed-10537688 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-105376882023-09-29 Enhancing Anti-SARS-CoV-2 Neutralizing Immunity by Genetic Delivery of Enveloped Virus-like Particles Displaying SARS-CoV-2 Spikes Yang, Yongping Kong, Wing-Pui Liu, Cuiping Ruckwardt, Tracy J. Tsybovsky, Yaroslav Wang, Lingshu Wang, Shuishu Biner, Daniel W. Chen, Man Liu, Tracy Merriam, Jonah Olia, Adam S. Ou, Li Qiu, Qi Shi, Wei Stephens, Tyler Yang, Eun Sung Zhang, Baoshan Zhang, Yi Zhou, Qiong Rawi, Reda Koup, Richard A. Mascola, John R. Kwong, Peter D. Vaccines (Basel) Article New vaccine delivery technologies, such as mRNA, have played a critical role in the rapid and efficient control of SARS-CoV-2, helping to end the COVID-19 pandemic. Enveloped virus-like particles (eVLPs) are often more immunogenic than protein subunit immunogens and could be an effective vaccine platform. Here, we investigated whether the genetic delivery of eVLPs could achieve strong immune responses in mice as previously reported with the immunization of in vitro purified eVLPs. We utilized Newcastle disease virus-like particles (NDVLPs) to display SARS-CoV-2 prefusion-stabilized spikes from the WA-1 or Beta variant (S-2P or S-2Pᵦ, respectively) and evaluated neutralizing murine immune responses achieved by a single-gene-transcript DNA construct for the WA-1 or Beta variant (which we named S-2P-NDVLP-1T and S-2Pᵦ-NDVLP-1T, respectively), by multiple-gene-transcript DNA constructs for the Beta variant (S-2Pᵦ-NDVLP-3T), and by a protein subunit–DNA construct for the WA-1 or Beta variant (S-2P-TM or S-2Pᵦ-TM, respectively). The genetic delivery of S-2P-NDVLP-1T or S-2Pᵦ-NDVLP-1T yielded modest neutralizing responses after a single immunization and high neutralizing responses after a second immunization, comparable to previously reported results in mice immunized with in vitro purified S-2P-NDVLPs. Notably, genetic delivery of S-2Pᵦ-NDVLP-3T yielded significantly higher neutralizing responses in mice after a second immunization than S-2Pᵦ-NDVLP-1T or S-2Pᵦ-TM. Genetic delivery also elicited high spike-specific T-cell responses. Collectively, these results indicate that genetic delivery can provide an effective means to immunize eVLPs and that a multiple-gene transcript eVLP platform may be especially efficacious and inform the design of improved vaccines. MDPI 2023-08-31 /pmc/articles/PMC10537688/ /pubmed/37766115 http://dx.doi.org/10.3390/vaccines11091438 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Yang, Yongping Kong, Wing-Pui Liu, Cuiping Ruckwardt, Tracy J. Tsybovsky, Yaroslav Wang, Lingshu Wang, Shuishu Biner, Daniel W. Chen, Man Liu, Tracy Merriam, Jonah Olia, Adam S. Ou, Li Qiu, Qi Shi, Wei Stephens, Tyler Yang, Eun Sung Zhang, Baoshan Zhang, Yi Zhou, Qiong Rawi, Reda Koup, Richard A. Mascola, John R. Kwong, Peter D. Enhancing Anti-SARS-CoV-2 Neutralizing Immunity by Genetic Delivery of Enveloped Virus-like Particles Displaying SARS-CoV-2 Spikes |
title | Enhancing Anti-SARS-CoV-2 Neutralizing Immunity by Genetic Delivery of Enveloped Virus-like Particles Displaying SARS-CoV-2 Spikes |
title_full | Enhancing Anti-SARS-CoV-2 Neutralizing Immunity by Genetic Delivery of Enveloped Virus-like Particles Displaying SARS-CoV-2 Spikes |
title_fullStr | Enhancing Anti-SARS-CoV-2 Neutralizing Immunity by Genetic Delivery of Enveloped Virus-like Particles Displaying SARS-CoV-2 Spikes |
title_full_unstemmed | Enhancing Anti-SARS-CoV-2 Neutralizing Immunity by Genetic Delivery of Enveloped Virus-like Particles Displaying SARS-CoV-2 Spikes |
title_short | Enhancing Anti-SARS-CoV-2 Neutralizing Immunity by Genetic Delivery of Enveloped Virus-like Particles Displaying SARS-CoV-2 Spikes |
title_sort | enhancing anti-sars-cov-2 neutralizing immunity by genetic delivery of enveloped virus-like particles displaying sars-cov-2 spikes |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10537688/ https://www.ncbi.nlm.nih.gov/pubmed/37766115 http://dx.doi.org/10.3390/vaccines11091438 |
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