Vaccine Development
Messenger RNA (mRNA) based vaccines are an emerging modality for vaccination, offering alternatives to live and subunit vaccines. mRNA vaccines encode one or more antigens, expressed by transfected cells. Because the antigen is expressed intracellularly, it elicits different MHC class responses than a subunit vaccine, and the mRNA itself acts as an adjuvant, boosting immunity. Researchers are currently developing mRNA vaccines for infectious diseases, and in contrast to traditional vaccines, mRNA vaccines can be mass produced at relatively low cost and turn-around times. Plasmid manufacturing processes have been developed that are optimized for therapeutic mRNA production, further increasing the viability of this method. For this reason, there is significant interest in these types of vaccines to counter pandemics or bioterrorism events.
Recently, there has been significant interest in use of mRNA vaccines for cancer, as they can be tailored to common cancer antigens, or personalized for individual cancer patients. In the individualized approach, a patient’s tumor is sequenced to identify neoantigens found in the tumor but not in somatic tissues. Then, a specialized vaccine expressing several patient specific neoantigens is produced.
mRNAs can also be used to prime dendritic cells to present antigens. Dendritic cells can be transfected ex vivo or in vivo, later recruiting immune cells to target the aforementioned antigens.
In addition, there is an emerging interest in vaccines based on self-replicating RNAs adapted from alpha viruses. The structural genes of the alpha virus are replaced with a payload to be expressed. Once transfected into cells, the self-replicating RNA expresses the viral polymerase and initiates several rounds of RNA replication. However, because the self-replicating RNA lacks capsid proteins, it cannot produce an infectious virus. As the self-replicating RNA replicates through a double stranded intermediate, it activates pattern recognition receptors that recognize double stranded RNA, inducing an adjuvant effect. Moreover, because it replicates, very low immunization doses are required.