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XBB.1.16-RBD-based trimeric protein vaccine can effectively inhibit XBB.1.16-included XBB subvariant infection
Dandan Peng1, Cai He1, Zimin Chen1
1Laboratory of Aging Research and Cancer Drug Target, State Key Laboratory of Biotherapy and Cancer Center, National Clinical Research Center for Geriatrics West China Hospital Sichuan University Chengdu Sichuan China.
Abstract:
The newly identified XBB.1.16-containing sublineages, including XBB.1.5, have become the prevailing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant in circulation. Unlike previous Omicron XBB variants (e.g., XBB.1.5 and XBB.1.9) harboring the F486P substitution, XBB.1.16 also carries a T478R substitution in the receptor-binding domain (RBD). Numerous researchers have delved into the high transmissibility and immune evasion of XBB.1.16 subvariant. Therefore, developing a new vaccine targeting XBB.1.16, including variants of concern (VOCs), is paramount. In our study, we engineered a recombinant protein by directly linking the S-RBD sequence of the XBB.1.16 strain of SARS-CoV-2 to the sequences of two heptad repeat sequences (HR1 and HR2) from the SARS-CoV-2 S2 subunit. Named the recombinant RBDXBB.1.16-HR/trimeric protein, this fusion protein autonomously assembles into a trimer. Combined with an MF59-like adjuvant, the RBDXBB.1.16-HR vaccine induces a robust humoral immune response characterized by high titers of neutralizing antibodies against variant pseudovirus and authentic VOCs and cellular immune responses. Additionally, a fourth heterologous RBDXBB.1.16-HR vaccine enhances both humoral and cellular immune response elicited by three-dose mRNA vaccines. These findings demonstrate that the recombinant RBDXBB.1.16-HR protein, featuring the new T478R mutation, effectively induces solid neutralizing antibodies to combat newly emerged XBB variants.
Insights
A new recombinant protein vaccine targeting the SARS-CoV-2 XBB.1.16 variant, featuring the T478R mutation, effectively induces neutralizing antibodies. This vaccine candidate shows promise for combating current and emerging severe acute respiratory syndrome coronavirus 2 variants.
Area of Science:
- Virology
- Immunology
- Vaccine Development
Background:
- The SARS-CoV-2 XBB.1.16 sublineage, characterized by the T478R substitution in the receptor-binding domain (RBD), is a prevalent variant of concern.
- Existing Omicron XBB variants like XBB.1.5 and XBB.1.9 possess the F486P substitution, differing from XBB.1.16.
- High transmissibility and immune evasion properties of XBB.1.16 necessitate the development of targeted vaccines.
Purpose of the Study:
- To engineer and evaluate a novel recombinant protein vaccine targeting the SARS-CoV-2 XBB.1.16 variant.
- To assess the immunogenicity of the recombinant RBDXBB.1.16-HR protein vaccine in inducing humoral and cellular immune responses.
Main Methods:
- Engineered a fusion protein linking the S-RBD of SARS-CoV-2 XBB.1.16 to heptad repeat sequences (HR1 and HR2) from the S2 subunit, forming a trimeric structure.
- Formulated the recombinant protein with an MF59-like adjuvant to create the RBDXBB.1.16-HR vaccine.
- Assessed vaccine efficacy by measuring neutralizing antibody titers against pseudoviruses and authentic variants of concern, and evaluating cellular immune responses. Investigated the effect of a heterologous fourth dose.
Main Results:
- The RBDXBB.1.16-HR vaccine, formulated with an MF59-like adjuvant, induced robust humoral immune responses with high neutralizing antibody titers against SARS-CoV-2 variants.
- Significant cellular immune responses were observed following vaccination.
- A fourth heterologous dose of the RBDXBB.1.16-HR vaccine boosted both humoral and cellular immunity in individuals previously vaccinated with mRNA vaccines.
Conclusions:
- The recombinant RBDXBB.1.16-HR protein vaccine effectively elicits strong neutralizing antibodies against emerging SARS-CoV-2 XBB variants, including those with the T478R mutation.
- This vaccine candidate holds potential for combating current and future severe acute respiratory syndrome coronavirus 2 variants.
- Heterologous boosting with the RBDXBB.1.16-HR vaccine can enhance immune responses generated by existing mRNA vaccine platforms.
