Recently, the research group of Professor Dong Mingxin of the School of Pharmacy of Qingdao University, the research team of Zhong Hui of the Military Medical Research Institute and the research team of Professor Wang Wei of the School of Medicine of Ocean University of China have made important progress in the research of new strategies for live attenuated influenza A vaccine. The research results were published online in ACS Synthetic Biology, a professional journal in the field of synthetic biology.
As many as 650,000 people die from seasonal influenza virus infection worldwide every year, and nearly 2.5 million people have died globally since the epidemic, and the prevention and control of pathogenic viruses remains one of the urgent global public health problems.
Vaccination has proven to be the most efficient and powerful way to prevent viral diseases. However, commercially available vaccines against coronavirus and influenza viruses have limited effectiveness in real-world immune protection. Preserving all antigens of the virus to the greatest extent and rapidly constructing a universal method of highly mutated live virus vaccines has always been the goal pursued by vaccine workers.
Currently, most vaccines rely on inactivated or attenuated technologies, but both technologies have their limitations and associated potential problems. Inactivated vaccines are generally harmless and non-contagious, but produce an immune response that lasts for a short time and requires multiple injections to enhance their overall immunogenicity. Live attenuated vaccines retain most of the genetic sequences of live viruses, have the advantages of strong immunity and long action time, but still have potential pathogenic risks.
There are various strategies for the production of live attenuated vaccines, including viruses carrying early stop codons, highly interferon-sensitive viruses, and protein degradation-targeted chimeric viruses. Current attenuation strategies are often accompanied by a loss or loss of safety, effectiveness, or productivity.
In addition, immune evasion due to persistent antigen drift and metastasis in seasonal influenza poses significant challenges to the efficacy of conventional influenza vaccines. Therefore, improving the safety and efficacy of live attenuated vaccines is an important direction of current vaccine research and development.
The research team successfully constructed a small molecule 4-HT-dependent influenza live attenuated vaccine by synthetic biology using peptide-containing self-splicing technology, and confirmed in vitro and in vitro experiments that the small molecule-dependent influenza A virus is less virulent than that of wild type, and can stimulate an innate immune response comparable to that of wild type virus.
In addition, animal experiments have shown that the constructed replication-deficient virus can induce strong and widespread humor, mucosal and cellular immunity to resist the attack of homologous viruses.
This research result has important theoretical significance and application prospects for the development of safe and effective influenza vaccines against influenza pandemics on a global scale, in addition, this is a general technology that may be applicable to many other viral systems, such as novel coronavirus and HIV, which may provide new ideas for the development of new coronavirus and HIV vaccines.
Schematic diagram of the production and induced immune response of H1N1 influenza virus Courtesy of the research group
The research was supported by a grant from the National Key Research and Development Program of China. (Source: China Science News, Liao Yang, Guo Shujun)
Related paper information:https://doi.org/10.1021/acssynbio.3c00020