A recombinant protein vaccine induces protective immunity against SARS-CoV-2 JN.1 and XBB-lineage subvariants

Signal Transduction and Targeted Therapy, Journal Year: 2025, Volume and Issue: 10(1)

Published: Feb. 25, 2025

Abstract The emergence of XBB- and JN.1-lineages with remarkable immune evasion characteristics have led to rises in breakthrough infections within populations. In addition, the unfavorable impacts imprinting, stemming from continuous exposure antigens circulated viruses, been observed incline response against earlier lineages, thereby declining neutralization newly emerged Omicron subvariants. this, advancement next-generation vaccines COVID-19 targeting components new subvariants such as XBB-lineage is imperative. current study, a self-assembled trimeric recombinant protein (RBD XBB.1.5 -HR) was generated by concatenating sequences receptor binding domain (RBD) derived heptad-repeat 1 (HR1) HR2 spike S2 subunit. Adjuvanted-RBD -HR induced robust humoral cellular responses, characterized elevated JN.1-inculuded substantial population antigen-specific T memory cells. Protective immunity conferred RBD vaccine preserved post-immunization, evidenced germinal center B (GC B) follicular helper (Tfh) sustained potency, an increase cells (MBCs) long-lived plasma (LLPCs). showed favorable boosting effect when administered heterologously after three doses inactivated virus (IV) mRNA vaccines. Significantly, it provided protection live EG.5.1 viruses vivo. monovalent safety immunogenicity, neutralizing antibodies JN.1- individuals prior vaccinations. These findings highlight its clinical potential safeguarding circulating

Language: Английский

A chimeric adenovirus‐vectored vaccine based on Beta spike and Delta RBD confers a broad‐spectrum neutralization against Omicron‐included SARS‐CoV‐2 variants

MedComm, Journal Year: 2024, Volume and Issue: 5(5)

Published: April 27, 2024

Abstract Urgent research into innovative severe acute respiratory coronavirus‐2 (SARS‐CoV‐2) vaccines that may successfully prevent various emerging emerged variants, particularly the Omicron variant and its subvariants, is necessary. Here, we designed a chimeric adenovirus‐vectored vaccine named Ad5‐Beta/Delta. This was created by incorporating receptor‐binding domain from Delta variant, which has L452R T478K mutations, complete spike protein of Beta variant. Both intramuscular (IM) intranasal (IN) vaccination with Ad5‐Beta/Deta induced robust broad‐spectrum neutralization against BA.5‐included variants. IN immunization Ad5‐Beta/Delta exhibited superior mucosal immunity, manifested higher secretory IgA antibodies more tissue‐resident memory T cells (T RM ) in tract. The combination IM delivery capable synergically eliciting stronger systemic immune responses. Furthermore, demonstrated effective boosting implications after two dosages mRNA or subunit recombinant vaccine, indicating capacity for utilization as booster shot heterologous vaccination. These outcomes quantified favorable can provide protective immunity versus SARS‐CoV‐2 pre‐Omicron variants concern subvariants.

Language: Английский

Trivalent recombinant protein vaccine induces cross-neutralization against XBB lineage and JN.1 subvariants: preclinical and phase 1 clinical trials

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: Dec. 30, 2024

The immune escape capacities of XBB variants necessitate the authorization vaccines with these antigens. In this study, we produce three recombinant trimeric proteins from RBD sequences Delta, BA.5, and XBB.1.5, formulating a trivalent vaccine (Tri-Vac) an MF59-like adjuvant at 1:1:4 ratio. Tri-Vac demonstrates immunogenicity in female NIH mice, inducing cross-neutralization against various SARS-CoV-2 variants, including pre-Omicron Omicron BA.2.75, lineages. It elicits measurable antigen-specific T cell responses, germinal center B follicular helper effectively protecting live XBB.1.16 challenges. Protective immunity is maintained long-term, sustained neutralizing antibodies as well memory cells long-lived plasma observed by day 210 post-immunization. also serves candidate booster for enhancing after doses inactivated virus or mRNA vaccines. A phase 1 investigator-initiated trial was initiated to assess safety humans, focusing on primary endpoint adverse reactions within 7 days key secondary endpoints geometric mean titers (GMTs) serum 30 6 months post-vaccination, events serious post-vaccination. Preliminary data indicate has good immunogenicity, improving neutralization multiple JN.1, previously vaccinated individuals, highlighting its clinical potential variants. registration number ChiCTR2200067245.

Language: Английский