New Advances in Rabies mRNA Vaccine Development

Limitations of Traditional Rabies Vaccines

The rabies virus (RABV) causes rabies which stands out as a zoonotic disease with nearly certain fatality. Through post-exposure prophylaxis in which rapid antibody-mediated neutralization blocks virus entry into the central nervous system rabies prevention becomes possible. The current rabies prevention methods involve administering rabies immunoglobulin from immunized horses or human donors together with five doses of rabies vaccine. Around 17 million people each year receive vaccines and medical treatment following exposure to rabies. Multiple doses and high treatment costs result in incomplete protection through vaccines despite their potential effectiveness which leads to roughly 60,000 annual rabies-related deaths worldwide.

Traditional rabies vaccines mainly fall into two categories: inactivated vaccines and live-attenuated vaccines. Inactivated vaccines provide safety but present several significant limitations. Patients need to receive several vaccinations between three to five times to build enough immunity which requires them to follow the treatment schedule closely. Resource-poor regions face significant obstacles when trying to ensure people finish their entire vaccination schedule. The high production costs of inactivated vaccines restrict their availability throughout economically underdeveloped regions. While live-attenuated vaccines offer extended immunity they present safety hazards due to possible reversion mutations which can cause illness thereby generating apprehension about their application.

Current advancements in vaccine technology have led to the emergence of nucleic acid vaccines which require optimization strategies to become more effective.

The fast-paced development of biotechnology has introduced nucleic acid vaccines which now present fresh opportunities for the prevention of rabies through mRNA vaccines. These vaccines enable fast development of targeted immune reactions while offering reduced production periods and cost-effective manufacturing. Current mRNA rabies vaccines struggle to produce high antibody levels and show slower kinetics than the three-dose Rabipur (inactivated rabies vaccine). Scientists have implemented major initiatives to improve both the immunogenicity and practicality of the RABV-G mRNA vaccine in the post-COVID-19 pandemic period.

Incorporating IL-7 as an Adjuvant

The effectiveness of nucleic acid vaccines can be enhanced by using appropriate adjuvants together with viral structure optimization. IL-7 serves as an essential cytokine that controls lymphocyte proliferation and differentiation while it supports the maturation of both T cells and B cells.

Research team leader Lingli Wang engineered a composite mRNA vaccine containing IL-7 mRNA and RABV-G mRNA packaged within lipid nanoparticles (LNPs) for mouse model testing. The results were exciting: The antibody response measured as neutralizing titers was higher in the IL-7 mRNA and RABV-G mRNA vaccine compared to the RABV-G mRNA vaccine alone and remained elevated for six months. Research demonstrated IL-7 activated the JAK-STAT pathway leading to enhanced proliferation and differentiation of Tfh cells along with GC B cells and plasma cells that improved the humoral immune response.

Figure 2. IL-7 promotes the proliferation of Tfh cells, GC B cells and PCs in mice. (Source: Wang L, et al., 2024)