tetano
Editor, Senior Moderator
Front Cell Infect Microbiol
. 2026 Jan 30:15:1690554.
doi: 10.3389/fcimb.2025.1690554. eCollection 2025.
A broad-spectrum SARS-CoV-2 RBD vaccine with selected high-impact mutations and novel adjuvant induces durable T cell response and broad protection in mice
Xianying Chen[SUP] #[/SUP][SUP] 1 [/SUP], Yuzhen Zhang[SUP] #[/SUP][SUP] 1 [/SUP], Shimin Yang[SUP] #[/SUP][SUP] 1 [/SUP], Yan Chen[SUP] 2 [/SUP], Shengnan Qian[SUP] 1 [/SUP], Zhen Zhang[SUP] 1 [/SUP], Qianyun Liu[SUP] 1 [/SUP], Chengbao Ma[SUP] 1 [/SUP], Weiyi Yu[SUP] 1 [/SUP], Jiangpeng Feng[SUP] 1 [/SUP], Jiejie Liu[SUP] 1 [/SUP], Ming Guo[SUP] 1 [/SUP], Zhixiang Huang[SUP] 1 [/SUP], Xin Wang[SUP] 1 [/SUP], Jie Chen[SUP] 1 [/SUP], Haiyan Zhao[SUP] 1 [/SUP], Huan Yan[SUP] 1 [/SUP], Ke Lan[SUP] 1 [/SUP], Yu Chen[SUP] 1 [/SUP], Li Zhou[SUP] 1 [/SUP]
Affiliations
Introduction: The emergence of new SARS-CoV-2 variants with immune evasion capabilities underscores the importance of developing a broad-spectrum and effective vaccine. The receptor binding domain (RBD) of the Spike protein has been widely utilized in vaccine due to its high immunogenicity. However, the Spike protein, particularly the RBD region, exhibits significant variability in the evolution of SARS-CoV-2, leading to viral immune evasion and reduced vaccine effectiveness.
Methods: A broad-spectrum antigen (M5-RBD) was developed via mutation patching, incorporating key high-impact mutation sites (K417T, L452R, T478K, E484K, N501Y). Additionally, extra mutations (N440K or G446S) were introduced into M5-RBD to evaluate their impact on immune response. M5-RBD was further combined with a novel CpG adjuvant HP007 for immunization.
Results: M5-RBD elicited high titers of broad-spectrum neutralizing antibodies against SARS-CoV-2 wild-type and various variants (Delta, Omicron BA.1, BA.2, BA.2.75, BA.5, BF.7, BQ.1.1, XBB, EG.5, JN.1, KP.3 strains). Introduction of N440K or G446S significantly diminished the immune response to viral strains. When combined with HP007 adjuvant, M5-RBD induced efficient and durable T cell responses, providing protection to K18-hACE2 KI mice against lethal infections with both wild-type and Omicron BA.2 strains.
Discussion: Rationally designed with key high-impact mutation sites, M5-RBD effectively overcomes SARS-CoV-2 variant immune evasion and elicits broad-spectrum neutralizing antibodies. The combination with HP007 adjuvant enhances immune protection, providing a promising strategy for the development of next-generation COVID-19 vaccines.
Keywords: CpG adjuvant; SARS-CoV-2; high-impact mutations; subunit vaccine; variants of concern.
. 2026 Jan 30:15:1690554.
doi: 10.3389/fcimb.2025.1690554. eCollection 2025.
A broad-spectrum SARS-CoV-2 RBD vaccine with selected high-impact mutations and novel adjuvant induces durable T cell response and broad protection in mice
Xianying Chen[SUP] #[/SUP][SUP] 1 [/SUP], Yuzhen Zhang[SUP] #[/SUP][SUP] 1 [/SUP], Shimin Yang[SUP] #[/SUP][SUP] 1 [/SUP], Yan Chen[SUP] 2 [/SUP], Shengnan Qian[SUP] 1 [/SUP], Zhen Zhang[SUP] 1 [/SUP], Qianyun Liu[SUP] 1 [/SUP], Chengbao Ma[SUP] 1 [/SUP], Weiyi Yu[SUP] 1 [/SUP], Jiangpeng Feng[SUP] 1 [/SUP], Jiejie Liu[SUP] 1 [/SUP], Ming Guo[SUP] 1 [/SUP], Zhixiang Huang[SUP] 1 [/SUP], Xin Wang[SUP] 1 [/SUP], Jie Chen[SUP] 1 [/SUP], Haiyan Zhao[SUP] 1 [/SUP], Huan Yan[SUP] 1 [/SUP], Ke Lan[SUP] 1 [/SUP], Yu Chen[SUP] 1 [/SUP], Li Zhou[SUP] 1 [/SUP]
Affiliations
- PMID: 41693861
- PMCID: PMC12901505
- DOI: 10.3389/fcimb.2025.1690554
Introduction: The emergence of new SARS-CoV-2 variants with immune evasion capabilities underscores the importance of developing a broad-spectrum and effective vaccine. The receptor binding domain (RBD) of the Spike protein has been widely utilized in vaccine due to its high immunogenicity. However, the Spike protein, particularly the RBD region, exhibits significant variability in the evolution of SARS-CoV-2, leading to viral immune evasion and reduced vaccine effectiveness.
Methods: A broad-spectrum antigen (M5-RBD) was developed via mutation patching, incorporating key high-impact mutation sites (K417T, L452R, T478K, E484K, N501Y). Additionally, extra mutations (N440K or G446S) were introduced into M5-RBD to evaluate their impact on immune response. M5-RBD was further combined with a novel CpG adjuvant HP007 for immunization.
Results: M5-RBD elicited high titers of broad-spectrum neutralizing antibodies against SARS-CoV-2 wild-type and various variants (Delta, Omicron BA.1, BA.2, BA.2.75, BA.5, BF.7, BQ.1.1, XBB, EG.5, JN.1, KP.3 strains). Introduction of N440K or G446S significantly diminished the immune response to viral strains. When combined with HP007 adjuvant, M5-RBD induced efficient and durable T cell responses, providing protection to K18-hACE2 KI mice against lethal infections with both wild-type and Omicron BA.2 strains.
Discussion: Rationally designed with key high-impact mutation sites, M5-RBD effectively overcomes SARS-CoV-2 variant immune evasion and elicits broad-spectrum neutralizing antibodies. The combination with HP007 adjuvant enhances immune protection, providing a promising strategy for the development of next-generation COVID-19 vaccines.
Keywords: CpG adjuvant; SARS-CoV-2; high-impact mutations; subunit vaccine; variants of concern.