A Snapshot of Progress in mRNA and DNA vaccines
An ounce of prevention is worth a pound of cure- Benjamin Franklin.
What are vaccines?
Vaccines are prophylactics designed to safely introduce epitopes of bacteria or viruses to your immune system to stimulate a response unique to the antigen.¹ The specific immunity generated by this process encourages a robust response in the event you encounter the bacteria or virus in everyday life, keeping your from getting sick.² There are a variety of types of vaccines:inactivated, attenuated (live) vaccines, subunit/conjugate, or recombinant vaccines each with its own set of advantages and disadvantages.³
Inactivated and attenuated vaccines contain bacteria or viruses that have been rendered completely inactive or have been weakened to such a state they pose little threat of infection.² The former generally induces a weaker response and often these vaccines require multiple doses over time to produce or maintain sufficient immune response, while the latter often poseselevated risk to those who are immunocompromised and often requires intensely monitored storage conditions.³
To increase immune response and to exposure to a greater number of epitopes in a single injection, subunit vaccines began being developed. These types of vaccines isolate specific parts of the bacteria, virus, or produced toxins to present to your immune system to make them competentto the antigen.³
Several of these units can be combined together to expose multiple antigens at the same time or units can be conjugated together as weak and/or strong antigens (often as polysaccharide and protein pairs) to improve immune response.⁴ Recombinant proteins can be produced from manipulating the original genetic code to enhance vaccine efficacy or increase the number of exposed antigens in a single dose, and to aid production via an alternative host cell that is more amenable to cultivation.⁵⁻⁷
Newly developed vaccine types are under development and utilize the bodies cellular machinery to improve immune response and reduce the chances of side effects.⁸ DNA vaccines encourage your own cells to produce the protein from the injected sequence, thereby exposing your immune system without any risk of infection. These plasmids are easier to produce, require less stringent storage measures, and tend to last a lot longer than the aforementioned vaccines.⁹
There is some risk of accidental DNA integration in the host as well as inadvertent development of immune responses to DNA.8 To date no such vaccine has been approved for human use, however, there is much optimism around this modality.⁹
mRNA vaccines also utilize your cells native machinery to produce the protein of interest but do so in a fashion that is theoretically less risky than DNA vaccines. mRNA is translated into proteins in the cytosol, there is no need to nuclear colocalization, and therefore no risk of host genomic integration.¹⁰ mRNA vaccines can be engineered to be less non-specifically immunostimulatory through a variety of means.¹¹
mRNA vaccines can also be modified to increase the intensity of the antigen production.¹⁰ Still, there is some risk of unintended immune response.¹² However, there are many companies pursuing this technology that has the potential to revolutionize the application of vaccines to cancers or genetic diseases.¹²
Purilogics is proud to support the production of all of these vaccine types with our novel purification technologies. Our Purexa™ NAEX Plus and Purexa™ MQ membrane chromatography products can be adapted for the purification of virus vectors, vaccines, DNA, and proteins.
We currently have affinity membranes in development for viruses, recombinant proteins, and mRNA. Our membrane technologies are designed to significantly increase purification productivity and accelerate the dissemination of vaccine technologies to the world.
References:
1. Greenwood, B. The Contribution of Vaccination to Global Health: Past, Present and Future. Philos. Trans. R. Soc. London. Ser. B, Biol. Sci.2014, 369 (1645), 20130433. https://doi.org/10.1098/rstb.2013.0433.
2. The College of Physicians of Philadelphia. Types of Vaccines https://www.historyofvaccines.org/content/types-vaccines.
3. U.S. Department of Health and Human Services (HHS). Vaccine Type https://www.vaccines.gov/basics/types.
4. Plotkin, S. History of Vaccination. PNAS2014, 111 (34), 12283–12287. https://doi.org/10.1073/pnas.1400472111.
5. Centers for Disease Control and Prevention. Quadrivalent Influenza Vaccine https://www.cdc.gov/flu/prevent/quadrivalent.html.
6. SpringerNature. Recombinant vaccine https://www.nature.com/subjects/recombinant-vaccine.
7. Rosano, G. L.; Ceccarelli, E. A. Recombinant Protein Expression in Escherichia Coli: Advances and Challenges. Front. Microbiol.2014, 5, 172. https://doi.org/10.3389/fmicb.2014.00172.
8. Ferraro, B.; Morrow, M. P.; Hutnick, N. A.; Shin, T. H.; Lucke, C. E.; Weiner, D. B. Clinical Applications of DNA Vaccines : Current Progress. Vaccines2011, 53, 296–302. https://doi.org/10.1093/cid/cir334.
9. Hobernik, D.; Bros, M. DNA Vaccines-How Far From Clinical Use? Int. J. Mol. Sci.2018, 19 (11). https://doi.org/10.3390/ijms19113605.
10. Pardi, N.; Hogan, M. J.; Porter, F. W.; Weissman, D. MRNA Vaccines — a New Era in Vaccinology. Nat. Rev. Drug Discov.2018, 17 (4), 261–279. https://doi.org/10.1038/nrd.2017.243.
11 Schlake, T.; Thess, A.; Fotin-mleczek, M.; Kallen, K. Developing MRNA-Vaccine Technologies. RNA Biol.2012, 9 (11), 1319–1330.
12. phg foundation. RNA vaccines: an introduction https://www.phgfoundation.org/briefing/rna-vaccines.