Self-Amplifying mRNA Vaccines

Self-amplifying mRNA vaccines have many advantages over conventional mRNA vaccines, although the production process is more challenging and requires improvement. Self-amplifying mRNA vaccines elicit more potent immune responses than the conventional mRNA vaccines thanks to the higher levels of antigen expression for a longer period of time as well as a strong intrinsic adjuvant effect. Therefore, it shows low effective dosage that may facilitate scale-up and manufacturing large numbers of vaccine doses. Moreover, self-amplifying mRNA vaccines have the ability to encode multiple antigens in the same replicon. Creative Biogene has established a self-amplifying mRNA vaccine platform that can produce single- or multi-antigen vaccines at a sufficient quantity and quality to meet regulatory requirements.

Fig.1 Schematic Representation of mRNA Vaccines and Mechanism of Antigen Expression. (Kowalski, P. S., et al, 2019)

Advantages of self-amplifying mRNA vaccines

Non-replicating mRNA and self-amplifying mRNA both have in common a 5' cap structure, untranslated regions (5' and 3' UTRs), an open-reading frame (ORF), and a 3' poly(A) tail. Different from non-replicating mRNAs, self-amplifying mRNA has the inclusion of genetic replication machinery derived from positive-stranded mRNA viruses, such as alphaviruses and flaviviruses. Based on the engineered RNA genome of positive-stranded RNA viruses, the RNA can encode both the antigen and the viral replication machinery that are able to direct intracellular mRNA amplification. Self-amplifying mRNA vaccines have multiple superiorities, including

• Higher immune potency: The self-amplifying mRNA vaccines express much higher levels of the protein for a longer period of time than the conventional mRNA vaccine. Besides, the existence of dsRNA amplification not only activates innate immunity, but also confers an adjuvant effect.
• More safety: The vaccines are unlikely to produce infectious virions or virus-like vesicles since their replicons lack endogenous viral structural genes. They are safer than attenuated virus vaccines.
• Low effective immunization dosage: Intracellular self-amplification and strong intrinsic adjuvant effect reduce the need for immunization dosage.
• Allowing the development of single- or multi-antigen vaccines: Having the ability to encode multiple antigens in the same replicon.

Our self-amplifying mRNA vaccine platform

We have established a self-amplifying mRNA vaccine platform based on self-replicating RNAs adapted from alphaviruses. The RNA genome of alphavirus is typically around 10–11 kb and encodes four non-structural proteins that form the RNA-dependent RNA polymerase (RDRP) complex. The RNA genomes of alphavirus have a dual function. They act as an mRNA template for the instant translation of RDRP, as well as a genomic template for replication by the respective RDRP. Self-amplifying mRNA replicons are created by replacing viral structural genes with the antigen gene of interest. Once transfected into cells, the self-replicating RNA expresses the viral polymerase and initiates RNA amplification to express high levels of the antigen of interest. We can offer self-amplifying mRNA design, manufacturing, and quality and potency evaluation using our technology platform.

Creative Biogene is passionate about strong customer orientation and high-quality service. With professional scientists and extensive experience in the field of mRNA-based drug R&D, we can produce self-amplifying mRNA vaccines in a rapid and scalable manner. Are you interested in our services? Please don't hesitate to contact us for more details.