Viral Vector Vaccine

Written by Christina Young and Edited by Alexander Alva

While viruses can cause disease and have their own ill connotations, viruses have become an indispensable tool in furthering our understanding of the human body as a type of novel technology. Viruses, on their own, are not “alive” in the traditional sense. They need to overtake another organism in order to activate and replicate; otherwise they remain inert and unable to do anything [1]. Due to this aspect of their “lifecycle,” different viruses use many different mechanisms to enter a cell, where they will shut down natural processes so that only virus particles become produced.

Vaccines, which are meant to prevent major adverse outcomes from an infection, have unexpectedly been revolutionized by the study of viruses. As drugs that introduce a disease-causing agent, called a pathogen, to an individual’s immune system without causing that disease, vaccines prime one’s immune system to better fight off such infections. Current vaccine categories include disabled pathogens (also known as live attenuated vaccines), killed, subunit, and recombinant vaccines, as well as those based on DNA and RNA, a precursor to proteins [2]. As of more recently, another vaccine mechanism being explored are viral vector vaccines. Viral vector vaccines utilize a modified, inert virus (vector) to deliver genetic information about a current, unmodified disease-causing virus, priming the immune system to recognize pieces of that disease-causing virus [3].

One example of a typically studied viral vector vaccine uses adenoviruses, a larger, non-enveloped virus, that is known to cause a number of childhood infections and diseases[4]. Due to some infections not causing symptoms, the actual prevalence of adenovirus infections remains unknown. Adenoviruses have a small enough size—about 92 nanometers—that can easily enter a cell. There, they would release genetic information that would send one’s body into overdrive to learn and recognize the disease-causing virus to prevent further infections from that particular virus [4]. Such vaccination systems have been used to combat HIV-1 in humans, as well as Ebola in chimpanzees [5] [6].

Some of the major benefits of using a viral vector vaccine, rather than other vaccine mechanisms, includes the targeting of these systems to specific cells in the body that can be targeted but specific infections. Moreover, adenoviruses are not hard to engineer due to their large enough size (for a virus) and their DNA components, the genetic material in all living organisms [7]. Unlike live attenuated and even killed vaccines, who have some chance to revert to an infectious pathogen, viral vectors have no chance of this due to the safety measures put in place during the modification process. Some of the current drawbacks of these, though, include the cost of engineering and possible immune recognition of the adenovirus vector in a person previously infected, which would prevent the vector from delivering its information in the first place [8]. Research is still on-going on how this system can be optimized and assist in the global strive towards preventing disease [9].

References:

1. Koonin, E.V., Starokadomskyy, P. (2016). Are viruses alive? The replicator paradigm sheds decisive light on an old but misguided question. Studies in History and Philosophy of Science Part C, 59:125-134.
2. “Vaccine Types” Vaccines.org, U.S. Department of Health & Human Services. https://www.vaccines.gov/basics/types. Accessed 14 Apr. 2021.
3. Ura, T., Okuda, K., Shimada, M. (2014). Developments in Viral Vector-Based Vaccines. Vaccines, 2:624-641.
4. Gray, G.C., Erdman, D.D. (2018). Adenovirus Vaccines. Plotkin’s Vaccines. e8:121-133. 
5. Barouch, D.H., Nabel, G.J. (2005). Adenovirus Vector-Based Vaccines for Human Immunodeficiency Virus Type 1. Human Gene Therapy, 16:146-156. 
6. Ledgerwood, J.E. DeZure, A.D., Stanley, D.A., Coates, E.E., Novik, L., Enama, M.E., Berkowitz, N.M., Hu, Z., Joshi, G., Ploquin, A., Sitar, S., Gordon, I.J., Plummer, S.A., Holman, L.A., Hendel, C.S., Yamshchikov, G., Roman, F., Nicosia, A, Colloca, S., Cortese, R., Bailer, R.T., Schwartz, R.M., Roederer, M., Mascola, J.R., Koup, R.A., Sullivan, N.J., Graham, B.S. (2017). Chimpanzee Adenovirus Vector Ebola Vaccine. New England Journal of Medicine, 376:928-938.
7. Ledgerwood, J.E. DeZure, A.D., Stanley, D.A., Coates, E.E., Novik, L., Enama, M.E., Berkowitz, N.M., Hu, Z., Joshi, G., Ploquin, A., Sitar, S., Gordon, I.J., Plummer, S.A., Holman, L.A., Hendel, C.S., Yamshchikov, G., Roman, F., Nicosia, A, Colloca, S., Cortese, R., Bailer, R.T., Schwartz, R.M., Roederer, M., Mascola, J.R., Koup, R.A., Sullivan, N.J., Graham, B.S. (2017). Chimpanzee Adenovirus Vector Ebola Vaccine. New England Journal of Medicine, 376:928-938.
8. Sharma, P.K., Dmitriev, I.P., Kashentseva, E.A., Raes, G., Li, L., Kim, S.W., Lu, Z.H., Arbeit, J.M., Fleming, T.P., Kaliberov, S.A, Goedegebuure, P., Curiel, D.T., Gillanders, W.E. (2017). Development of an adenovirus vector vaccine platform for targeting dendritic cells. Cancer Gene Therapy, 25:27-38. 
9. Yang, Z.Y., Wyatt, L.S., Kong, W.P., Moodie, Z., Moss, B., Nabel, G.J. (2003). Overcoming Immunity to a Viral Vaccine by DNA Priming before Vector Boosting. Journal of Virology, 77:799-803.[9] Cimolai, N. (2020). Preliminary concerns with vaccine vectors. Mutagenesis, 35:359-360.