mRNA vaccines against arthropod-borne orthofaviviruses

Arthropod-borne orthoflaviviruses, a group of single-stranded, positive-sense RNA viruses, are primarily transmitted to humans through the bites of mosquitoes or ticks. These viruses are significant human and veterinary pathogens, capable of causing severe and widespread diseases, including encephalitis, microcephaly, hepatitis, and arthritis. Orthoflaviviruses predominantly affect tropical and subtropical regions, putting over 3 billion individuals at risk of outbreaks. Historically, conventional vaccines, such as live attenuated and inactivated vaccines, have provided durable protection against various orthoflaviviruses, including yellow fever virus, tick-borne encephalitis virus, Japanese encephalitis virus, and dengue virus. These vaccines are critical tools for preventing millions of illnesses and saving numerous lives annually. However, the safety profiles and immunogenicities of these existing vaccines require ongoing enhancement and refinement. The advent of mRNA vaccines represents a promising alternative to conventional vaccines. mRNA vaccines utilize messenger RNA (mRNA) to instruct the body to produce virus-specific proteins. These proteins can mimic those of the virus, triggering the immune system to produce viral specific B cell and T cell responses capable of combating the real virus upon exposure. Over the past decade, major technological innovations and research investments have enabled mRNA vaccines to emerge as powerful immune efficacy compared to conventional vaccines. Importantly, they can offer several advantages over conventional vaccines, including high potency, proven safety and efficacy, rapid clinical development, and cost-effective manufacturing potential. These benefits make mRNA vaccines a significant tool in accelerating the development of safe and potent vaccines against emerging and re-emerging infectious diseases. Notably, during the SARSCoV-2 pandemic, the mRNA-1273 vaccine developed by Moderna and the BNT162b mRNA vaccines developed by Pfizer/ BioNTech received approval from the US Food and Drug Administration. Additionally, many mRNA vaccines targeting multiple infectious diseases have entered clinical trials. Consequently, mRNA vaccines will undoubtedly play a pivotal role in the rapid development of safe and effective orthofavivirus vaccines. Their ability to be rapidly designed and manufactured allows for a swift response to outbreaks and the emergence of new orthofavivirus strains. In this review, we initially summarize the molecular basis and mechanism of action of mRNA vaccines, including their structure, function, in vivo replication, and translation processes. Subsequently, we briefly introduce the biological characteristics of several important orthofaviviruses, including their genome, structures, life cycle, disease symptoms and epidemic trends. Furthermore, we focus on the current status of mRNA vaccines against these viruses, covering the selected antigens, mRNA technologies, immunization methods, subject populations, and the efficacies of various mRNA vaccines. Finally, we emphasize the roles of synthetic biology, nucleotide modification technologies and novel delivery systems in the development of mRNA vaccines. In conclusion, this review offers innovative research perspectives and technical insights to accelerate the development of efficient, safe and widely accessible mRNA vaccines for orthofaviruses in the future.