Understanding the Nucleic Acid Vaccines

Credit: MIT News


Faced with the challenges posed by infectious diseases and cancer, nucleic acid vaccines present excellent prospects in clinical applications. Compared with traditional vaccines, nucleic acid vaccines have the characteristics of high efficiency and low cost. Therefore, nucleic acid vaccines have potential advantages in disease prevention and treatment. However, the low immunogenicity and instability of nucleic acid vaccines have limited their development. Therefore, a large number of studies have been conducted to improve their immunogenicity and stability by improving delivery methods, thereby supporting progress and development for clinical applications.

What is Nucleic Acid Vaccines?

Instead of injecting a weakened form of a virus or bacteria into the body, Nucleic acid vaccines use genetic material from a disease-causing virus or bacterium (a pathogen) to stimulate an immune response against it. That immune response, which produces antibodies, is what protects us from getting infected if the real virus enters our bodies. Nucleic acid vaccines have the potential to be safe, effective, and cost-effective. Moreover, the immune responses induced by nucleic acid vaccines only target the selected antigen in the pathogen.

Types of Nucleic Acid Vaccine

Nucleic acid-based vaccines, including DNA (as plasmids) and RNA [as messenger RNA (mRNA)] vaccines, exhibit promising potential in targeting various indications and diseases.

What is DNA Vaccine?

DNA vaccines are generated by inserting a gene encoding antigens into a bacteria-derived plasmid, which needs to be controlled by a powerful promoter. DNA plasmids are replicated in bacteria, which can be selected based on antibiotic resistance mediated by genes carrying resistance markers, using the prokaryotic origin of replication. Additionally, DNA vaccines can affect not only humoral immunity but also cellular immunity. Although the precise mechanisms underlying the induction of an immune response to antigens expressed by host cells following DNA immunization have not yet been determined, we have a considerable understanding of the roles of immune cells in the processing, presentation, and recognition of antigens.

What is RNA Vaccine?

Currently, there are two widely acknowledged forms of mRNA vaccines, namely, non-amplifying mRNA and self-amplifying mRNA, which are classified due to the difference in mechanisms. In terms of structure, non-amplifying mRNA vaccines mainly contain five critical elements for the life cycle and expression: the “cap” [m7Gp3N(N: any nucleotide)], which is a 7-methyl-guanosine residue (m7G) bound to the 5′-end of the RNA transcript via a 5′–5′ triphosphate bond with any nucleotide; a 5′ untranslated region (5′UTR) that sits immediately upstream of the translation initiation codon; an open reading frame (ORF) encoding the gene of interest (GOI); a 3′ untranslated region (3′UTR); and a tail of 100–250 adenosine residues [poly(A) tail].

Advantages of Nucleic Acid Vaccine

Safe and non-infectious as they are not made with pathogen particles or inactivated pathogens.
Can generate a stronger type of immunity and are well tolerated as compared to traditional vaccines.
Can be produced more rapidly as they do not require a host for growth, e.g., eggs or bacteria.