New vaccine strategy targets SARS-CoV-2’s stable S2 subunit, offering broad protection against evolving variants
In a groundbreaking study, scientists have developed a new vaccine strategy that specifically targets the stable S2 subunit of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This innovative approach provides broad protection against evolving variants of the virus. The vaccine has shown promising results in animal tests, generating strong antibody responses against difficult-to-resolve variants. However, further research is needed to confirm its efficacy in humans and its long-term effectiveness against new SARS-CoV-2 variants.
The study, titled A broadly generalizable stabilization strategy for sarbecovirus fusion machinery vaccines, focused on stabilizing the prefusion state of the S2 subunit. By maintaining the subunit’s structure and antigenicity, the researchers aimed to enhance the immune response and improve the vaccine’s effectiveness against various sarbecovirus strains.
To achieve this, the scientists utilized various cell lines, including Human Embryonic Kidney 293 cells with SV40 T-antigen (HEK293T), Expi293F, and VeroE6-TMPRSS2. These cells were carefully cultivated and used to produce recombinant S2 antigen proteins. The proteins were then purified using specialized techniques, ensuring their quality and effectiveness for further experiments.
The team designed and produced several constructs, incorporating specific mutations and utilizing deep-mutational scanning data. These constructs exhibited favorable characteristics, such as monodispersity and high yields of purified protein. Through meticulous electron microscopy and cryo-electron microscopy analyses, the researchers confirmed the successful stabilization of the prefusion state of the S2 subunit trimer.
The stability and antigenicity of the vaccine candidates were also evaluated under different storage conditions. The results showed that the prefusion-stabilized vaccine retained its structural integrity and remained effective, even after freezing and thawing.
In animal tests on BALB/c mice, the E-69 vaccine candidate demonstrated robust immunogenicity, generating comparable antibody binding titers against SARS-CoV-2 variants and higher titers against SARS-CoV-1. Furthermore, the vaccine elicited the highest neutralizing antibody titers against the XBB.1.5 variant, highlighting its potential to induce broadly reactive antibody responses.
Although the vaccines did not prevent infection when the mice were challenged with the XBB.1.5 variant, the vaccinated mice were protected against weight loss and exhibited comparable viral titers. This suggests that the S2 subunit vaccine may offer protection against immune evasive SARS-CoV-2 variants.
The results of this study offer promising prospects for the development of an effective vaccine strategy that can target the stable S2 subunit of SARS-CoV-2, providing broad protection against evolving variants. However, it is important to note that the findings are preliminary and require further research and clinical trials to validate the vaccine’s efficacy in humans. With the evolving nature of the virus, continuous efforts are needed to combat emerging variants and ensure effective protection for global populations.
*Important notice: The study cited in this article was posted on the bioRxiv pre-print server and has not undergone peer review. Therefore, it should not be regarded as conclusive or treated as established information.
Journal reference: Preliminary scientific report. Jimin Lee, Cameron Stewart, Alexandra Schaefer, et al. A broadly generalizable stabilization strategy for sarbecovirus fusion machinery vaccines, bioRxiv, 2023, doi: https://doi.org/10.1101/2023.12.12.571160 https://www.biorxiv.org/content/10.1101/2023.12.12.571160v1
