In the post-pandemic era, it is particularly important for mRNA technology to be applied scientifically and rationally, and to continue to play a role in drug development in the fields of prevention of infectious diseases and treatment of major diseases. Recently, Emerging Microbes & Infections and NPJ Vaccines, internationally recognized journals in the field of vaccinology and infectious diseases, published the research results of Yang Yong/Lin Ang team in the fields of herpes zoster preventive mRNA vaccine and chronic hepatitis B therapeutic mRNA vaccine respectively.
Herpes zoster is highly prevalent in people aged 50 years and above, and the incidence of herpes zoster has been decreasing in recent years. Currently, GSK's herpes zoster vaccine, Shingrix, occupies the global herpes zoster vaccine market, and although it has superior protective power, it has problems such as high price, high side effects, and insufficient supply. Based on years of experience in basic and applied research on mRNA vaccines, the Yang Yong/Lin Ang team of our university has developed an mRNA vaccine encoding the full-length protein of viral gE, which covers more T cell epitopes and is significantly better than Shingrix in terms of inducing natural immune activation, virus-specific T and B cell responses, antibody response and Fc function, and safety, etc. The team has further developed the mechanism of immune response in vaccine, and has developed a comprehensive research program to study the mechanism of immune response in vaccine. The team further investigated the mechanism of immune response and identified immune markers related to the specific response of mRNA vaccine, suggesting that the transient elevation of special phagocyte population after vaccination may affect the immune efficacy of mRNA vaccine, which will provide a reference for the development of mRNA vaccine delivery vector.
Currently, nearly 240 million chronic hepatitis B patients exist worldwide, and clinical interferon and nucleoside analog-based therapies are unable to induce sustained virologic suppression. Clinically, the prolonged presence of serum HBsAg in chronic hepatitis B patients is one of the key factors in the progression of slow liver to cirrhosis and hepatocellular carcinoma. Although GalNAc-siRNA drugs, which have gained much attention in recent years, can target the virus itself, it is difficult to reverse the impairment of immune function caused by chronic HBV infection. Based on this, the team explored the potential of mRNA technology in chronic liver therapy for the first time in the world. The results showed that after three injections of HBV therapeutic mRNA vaccine, serum HBsAg of HBV mice was completely eliminated and did not rebound within the observation period of 208 days. In addition, the vaccine induced high levels of virus-neutralizing antibodies in HBV mice and successfully achieved seroconversion. In comparison with entecavir, the first-line therapeutic agent in the clinic, three doses of the mRNA vaccine were sufficient to achieve viral DNA clearance with entecavir administered for 15 consecutive days, but entecavir was unable to effectively clear serum HBsAg and did not induce the production of antiviral antibodies. This study provides new ideas for the development of therapeutic vaccines for chronic hepatitis B. The team is advancing the subsequent translation of this therapeutic vaccine.
The above work was supported by the Xingdao Youth Initiation Fund of China Pharmaceutical University, the Original Exploration Project Fund of the Central Universities, and the Youth Fund of Natural Science of Jiangsu Province, as well as collaborative support from Shandong University, Karolinska Institute of Sweden, Jiangnan University, Dalian Medical University, and other institutions.
Original Link:
https://www.tandfonline.com/doi/full/10.1080/22221751.2024.2309985
https://www.nature.com/articles/s41541-024-00813-3
