In response to the COVID-19 pandemic, Raghavan Varadarajan, a Professor at the Molecular Biophysics Unit (MBU) at the Indian Institute of Science (IISc), and his collaborators have been actively engaged in the development of a heat-tolerant vaccine capable of providing protection against various strains of the SARS-CoV-2 virus, including current and potential future variants.
Their groundbreaking study, published in npj Vaccines, details the creation of a synthetic antigen that holds promise as a viable COVID-19 vaccine candidate. What sets this vaccine apart is its effectiveness against all known current strains of SARS-CoV-2 and its adaptability to address emerging variants, which is particularly crucial considering the virus’s rapid mutation rates.
While existing vaccines have proven effective against many SARS-CoV-2 strains, their efficacy has been impacted by the virus’s ability to mutate quickly. To overcome this challenge, Varadarajan and his team delved into the analysis of various proteins within the virus and honed in on two components of the SARS-CoV-2 spike protein—the S2 subunit and the receptor binding domain (RBD).
The S2 subunit, known for its high conservation and lower mutation rates compared to the S1 subunit targeted by current vaccines, was combined with the RBD, recognized for provoking a robust immune response. The resultant hybrid protein, named RS2, was designed as the core of their vaccine candidate.
The researchers utilized mammalian cell lines to assess the expression levels of the RS2 hybrid protein. Remarkably, the protein exhibited exceptionally high expression, suggesting the potential for large-scale production. This characteristic is crucial for efficient mass production of the vaccine candidate.
Subsequent tests involved studying the effects of the RS2 protein in both mice and hamster models. The results were encouraging, indicating that the hybrid protein not only triggered a potent immune response but also provided enhanced protection compared to vaccines containing the entire spike protein. This represents a significant advancement in vaccine development, offering a more effective and adaptable solution against SARS-CoV-2.
One notable feature of the RS2 antigen is its stability at room temperature for up to a month without requiring cold storage. This stands in contrast to many existing vaccines that necessitate strict cold storage conditions. The ability to store the vaccine at room temperature for extended periods enhances its economic viability by simplifying distribution and storage logistics.
Varadarajan’s team initiated work on the vaccine even before the COVID-19 pandemic gained widespread prevalence in India. Drawing on their expertise gained since 2000, the team has been actively involved in designing various viral vaccines, including those targeting AIDS and influenza. This accumulated knowledge was leveraged to develop the RS2-based COVID-19 vaccine candidate, a collaborative effort with the startup Mynvax, formerly incubated at IISc.
According to the research team, the RS2-based vaccine candidate can be tailored to incorporate the RBD region of any new SARS-CoV-2 variant that may emerge. Its high expression levels and stability at room temperature offer significant cost reduction benefits in terms of production and distribution, making it a promising candidate in the ongoing global efforts to combat COVID-19.
Journal Reference
Nidhi Mittal et al, Enhanced protective efficacy of a thermostable RBD-S2 vaccine formulation against SARS-CoV-2 and its variants, npj Vaccines (2023). DOI: 10.1038/s41541-023-00755-2.
