Vaccines of the Past Make a Comeback

Updated: Jan 24


For generations scientists have been striving to cure cancer and eradicate infectious viruses, and new vaccine technology could help us make it a reality. With the growing use of the newfound COVID-19 mRNA vaccines from Moderna and Pfizer, DNA vaccines appeared to fade in history. Unlike the race for mRNA vaccine development, the DNA vaccine movement ended before it could start, having never made it past clinical trial stages. First synthesized in the 1990s with the promise of preventing HIV, HPV, and melanoma, the DNA vaccine only yielded incomplete immunity across a number of clinical trials [1]. Unsurprisingly, they were quickly outpaced by other kinds of vaccines that are still viable today. However, the recent strides made in India against COVID-19 show promise in DNA vaccine technology [2].


The drastic rise in COVID cases in India has impacted innovations in the worldwide pharmaceutical-producing capital. The development of the COVID DNA vaccine ZyCoV-D, designed by an Indian pharmaceutical company Zydus Cadila, is revolutionary on two fronts: it is derived from DNA and is needle-free. Johnson and Johnson's COVID vaccine, elicited from a virus incapable of replicating, has a 66.3% effectiveness. On the other hand, ZyCoV-D has a 67% effectiveness and is much easier to synthesize [3]. What has changed over the past three decades to show such drastic improvements? Recent research showcases that the main problem with DNA vaccines was the delivery method of the DNA for cellular uptake, which the needle-free system surpasses [1,4].


DNA vaccines are composed of plasmids, or rings of DNA, with the information needed to encode the spike protein that elicits an immune response. Compared to other forms of vaccines such as live-attenuated or inactivated vaccines, DNA vaccines are easier to transport, bear no risk of the virus replicating, and lack the need for booster shots [5]. A key aspect of DNA vaccines is their "plug and play" nature, meaning that new vaccines can be designed for any viruses or variants that arise by simply changing the modular components of the plasmid. Plasmids are found in bacteria, so they can be synthesized via bacterial cultures, specifically DH5-Alpha E. coli, through simple bacterial transformation protocols that facilitate vaccine production [4].


There may be even more pushback against DNA vaccines than mRNA vaccines over fear that the vaccines may alter human genetic code, but DNA vaccines are safe, with the vaccine plasmids degrading in weeks or months while immunity remains [2]. While it is true that the long term effects of adenovirus and mRNA COVID vaccines cannot be predicted as of yet, the chances of human DNA alterations are low, and the advantages of these vaccines significantly outweigh the potential negligible risks [6]. In fact, DNA vaccines could drastically change the lives of those living with severe health issues, and such an advantage should not be overlooked.


The clinical trials of the past are making a comeback. With the revitalization of DNA vaccine technology, clinical trials on preventing HIV infection and colorectal cancer progression, to name a few examples, are being developed [1]. Preventing these two illnesses specifically could have massive implications on Healthcare and quality of life for minorities, who are the predominant patients for both diseases in the U.S [7,8].


Upon observing the current healthcare landscape, it is evident that there is an inherent relationship between race and income that affects diet and related health outcomes in minorities. For example, low-income individuals may find it difficult to access healthy food options due to high costs. More affordable food options are typically high in saturated fat and sodium, which have negative long-term impacts on health. Minorities usually have lower income compared to their White counterparts, but it’s important to note that not all minorities have the same experience when low-income [9]. Although vaccines cannot fix the social determinants of health, they can help to mitigate the health outcomes disproportionately experienced by minority groups by providing immunity.


DNA vaccines have the potential to reduce strain in the Healthcare industry and diminish racial disparities. The moral implications of eliminating racial disparities in Healthcare, the potential to reduce annual Healthcare expenditure by nearly a quarter of a trillion dollars, and the increase in coverage that might improve the quality of life of millions are all persuasive reasons to advance research in DNA vaccination [10]. The overall mental health of minorities would also improve, as the added preventative measures in place via the DNA vaccines would help reduce cognitive load caused by high stress levels associated with poor health outcomes that disproportionately target this group [11]. Reducing cognitive load could improve socioeconomic status, as one becomes more inclined to save their money for future gain and increases productivity as demonstrated by higher memory capacity in a social experiment conducted by researchers [12].


The race has officially begun, and the ZyCoV-D vaccine is simply the first runner in the relay of technological and medical improvements. Developing biological vaccine delivery methods, such as outer membrane vesicles, and newly utilized mechanical vaccine delivery methods, such as needle-free injection technology, could both improve the systems developed for COVID-19 and future vaccines. The expansion in clinical trials of DNA vaccines is promising, as new clinical trials in preventing and treating COVID, late-stage melanoma, HIV, and colorectal cancer will be conducted globally. Treating these illnesses, which have evaded science for decades, would turn the tide on treating future diseases and improving current treatments.


References:

  1. Ferraro, B., Morrow, M. P., Hutnick, N. A., Shin, T. H., Lucke, C. E., & Weiner, D. B. (2011). Clinical applications of DNA vaccines: Current progress. Clinical Infectious Diseases : An Official Publication of the Infectious Diseases Society of America, 53(3), 296–302. PubMed. https://doi.org/10.1093/cid/cir334

  2. Mallapaty, S. (2021). India’s DNA COVID vaccine is a world first – more are coming. Nature, 597(7875), 161–162. https://doi.org/10.1038/d41586-021-02385-x

  3. Sharun, K., & Dhama, K. (2021). India’s role in COVID-19 vaccine diplomacy. Journal of Travel Medicine, 28(7). https://doi.org/10.1093/jtm/taab064

  4. Momin, T., Kansagra, K., Patel, H., Sharma, S., Sharma, B., Patel, J., Mittal, R., Sanmukhani, J., Maithal, K., Dey, A., Chandra, H., Rajanathan, C. T., Pericherla, H. P., Kumar, P., Narkhede, A., & Parmar, D. (2021). Safety and immunogenicity of a DNA SARS-CoV-2 vaccine (ZyCoV-D): Results of an open-label, non-randomized phase I part of phase I/II clinical study by intradermal route in healthy subjects in India. EClinicalMedicine, 38, 101020. https://doi.org/10.1016/j.eclinm.2021.101020

  5. Office of Infectious Disease and HIV/AIDS Policy (OIDP). (2021, May 4). Vaccine types. HHS.gov. Retrieved November 14, 2021, from https://www.hhs.gov/immunization/basics/types/index.html.

  6. Doerfler, W. (2021). Adenoviral vector DNA- and SARS-CoV-2 mRNA-based Covid-19 vaccines: Possible integration into the human genome—Are adenoviral genes expressed in vector-based vaccines? Virus Research, 302, 198466–198466. PubMed. https://doi.org/10.1016/j.virusres.2021.198466

  7. U.S. statistics. HIV.gov. (2021, June 2). Retrieved November 13, 2021, from https://www.hiv.gov/hiv-basics/overview/data-and-trends/statistics.

  8. Centers for Disease Control and Prevention. (2020, March 3). Colorectal cancer, United States-2007–2016. Centers for Disease Control and Prevention. Retrieved November 13, 2021, from https://www.cdc.gov/cancer/uscs/about/data-briefs/no16-colorectal-cancer-2007-2016.htm.

  9. Satia, J. A. (2009). Diet-related disparities: Understanding the problem and accelerating solutions. Journal of the American Dietetic Association, 109(4), 610–615. PubMed. https://doi.org/10.1016/j.jada.2008.12.019

  10. LaVeist, T. A., Gaskin, D., & Richard, P. (2011). Estimating the economic burden of racial health inequalities in the United States. International Journal of Health Services, 41(2), 231–238. https://doi.org/10.2190/HS.41.2.c

  11. Zeki Al Hazzouri, A., Elfassy, T., Sidney, S., Jacobs, D., Pérez Stable, E. J., & Yaffe, K. (2017). Sustained economic hardship and cognitive function: The coronary artery risk development in young adults study. American Journal of Preventive Medicine, 52(1), 1–9. PubMed. https://doi.org/10.1016/j.amepre.2016.08.009

  12. Deck, C., & Jahedi, S. (2015). The Effect of Cognitive Load on Economic Decision Making: A Survey and New Experiments. European Economic Review, 78, 97–119. https://doi.org/10.1016/j.euroecorev.2015.05.004


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