Enhancing vaccine half-life as a novel strategy for improving immune response durability of subunit vaccines.

Vaccines are widely regarded as one of the most effective strategies for combating infectious diseases. However, significant challenges remain, such as insufficient antibody levels, limited protection against rapidly evolving variants, and poor immune durability, particularly in subunit vaccines, li...

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Main Authors: Zhaoling Shen, Cheng Li, Wenping Song, Litong Liu, Yu Kong, Ailing Huang, Qingui Bao, Tianlei Ying, Yanling Wu
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2025-01-01
Series:PLoS Pathogens
Online Access:https://doi.org/10.1371/journal.ppat.1012845
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author Zhaoling Shen
Cheng Li
Wenping Song
Litong Liu
Yu Kong
Ailing Huang
Qingui Bao
Tianlei Ying
Yanling Wu
author_facet Zhaoling Shen
Cheng Li
Wenping Song
Litong Liu
Yu Kong
Ailing Huang
Qingui Bao
Tianlei Ying
Yanling Wu
author_sort Zhaoling Shen
collection DOAJ
description Vaccines are widely regarded as one of the most effective strategies for combating infectious diseases. However, significant challenges remain, such as insufficient antibody levels, limited protection against rapidly evolving variants, and poor immune durability, particularly in subunit vaccines, likely due to their short in vivo exposure. Recent advances in extending the half-life of protein therapeutics have shown promise in improving drug efficacy, yet whether increasing in vivo persistence can enhance the efficacy of subunit vaccines remains underexplored. In this study, we developed two trimeric SARS-CoV-2 subunit vaccines with distinct pharmacokinetic profiles to evaluate the impact of vaccine persistence on immune efficacy. A self-assembling trimeric subunit vaccine (RBD-HR/trimer) was designed, followed by an extended-persistence variant (RBD-sFc-HR/trimer) incorporating a soluble monomeric IgG1 fragment crystallizable. We demonstrated that RBD-sFc-HR/trimer elicited more robust and higher levels of neutralizing antibodies, with potent and broad neutralization activity against multiple SARS-CoV-2 variants. Notably, RBD-sFc-HR/trimer induced a durable immune response, significantly increasing the number of memory B cells and T cells. This study provides critical insights for designing vaccines that achieve potent and long-lasting immune responses against infectious diseases.
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institution OA Journals
issn 1553-7366
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publishDate 2025-01-01
publisher Public Library of Science (PLoS)
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spelling doaj-art-6c5057ae79cd4b40bf296f23dcb1ebb62025-08-20T02:20:33ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742025-01-01211e101284510.1371/journal.ppat.1012845Enhancing vaccine half-life as a novel strategy for improving immune response durability of subunit vaccines.Zhaoling ShenCheng LiWenping SongLitong LiuYu KongAiling HuangQingui BaoTianlei YingYanling WuVaccines are widely regarded as one of the most effective strategies for combating infectious diseases. However, significant challenges remain, such as insufficient antibody levels, limited protection against rapidly evolving variants, and poor immune durability, particularly in subunit vaccines, likely due to their short in vivo exposure. Recent advances in extending the half-life of protein therapeutics have shown promise in improving drug efficacy, yet whether increasing in vivo persistence can enhance the efficacy of subunit vaccines remains underexplored. In this study, we developed two trimeric SARS-CoV-2 subunit vaccines with distinct pharmacokinetic profiles to evaluate the impact of vaccine persistence on immune efficacy. A self-assembling trimeric subunit vaccine (RBD-HR/trimer) was designed, followed by an extended-persistence variant (RBD-sFc-HR/trimer) incorporating a soluble monomeric IgG1 fragment crystallizable. We demonstrated that RBD-sFc-HR/trimer elicited more robust and higher levels of neutralizing antibodies, with potent and broad neutralization activity against multiple SARS-CoV-2 variants. Notably, RBD-sFc-HR/trimer induced a durable immune response, significantly increasing the number of memory B cells and T cells. This study provides critical insights for designing vaccines that achieve potent and long-lasting immune responses against infectious diseases.https://doi.org/10.1371/journal.ppat.1012845
spellingShingle Zhaoling Shen
Cheng Li
Wenping Song
Litong Liu
Yu Kong
Ailing Huang
Qingui Bao
Tianlei Ying
Yanling Wu
Enhancing vaccine half-life as a novel strategy for improving immune response durability of subunit vaccines.
PLoS Pathogens
title Enhancing vaccine half-life as a novel strategy for improving immune response durability of subunit vaccines.
title_full Enhancing vaccine half-life as a novel strategy for improving immune response durability of subunit vaccines.
title_fullStr Enhancing vaccine half-life as a novel strategy for improving immune response durability of subunit vaccines.
title_full_unstemmed Enhancing vaccine half-life as a novel strategy for improving immune response durability of subunit vaccines.
title_short Enhancing vaccine half-life as a novel strategy for improving immune response durability of subunit vaccines.
title_sort enhancing vaccine half life as a novel strategy for improving immune response durability of subunit vaccines
url https://doi.org/10.1371/journal.ppat.1012845
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