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Pipeline Digs Deeper: The Vexing Vaccine Problem

2020 has been dominated by talks about Covid-19. With over a million dead, economies paralysed and thousands facing all manner of restrictions in their day-to-day lives, it doesn’t seem likely that we’ll ever be rid of COVID and the havoc it has wrought. In these trying times, the vaccine has been touted as a solution to bringing a much-needed sense of normality. The development of a viable vaccine has been promisingly quick so far, but how long will it be until one is widely available?


At the time of writing, there are 213 vaccines and 319 treatments in development for the virus (Milken Institute, 2020). These vaccines are making use of every technology available, from the more traditional live attenuated viral vaccines used against MMR which utilise a weakened version of the virus, to modern nucleic acid-based vaccines that have yet to be used on such a large scale (Callaway, 2020). It is the latter, particular RNA-based vaccines that have dominated headlines so far as the fastest vaccines to be developed, with the US Company Moderna going from DNA sequence to first shot in 63 days (Moderna Inc, 2020). These vaccines involve RNA sequences that code for viral proteins entering cells, causing them to produce the viral proteins and trigger an immune system response (Callaway, 2020). This is the approach being taken by the team at Imperial (Johns, 2020). Other vaccine approaches include using a dead version of the virus, using a viral vector to carry genetic material on the back of a harmless virus, or simply injecting viral proteins themselves (Callaway, 2020).


RNA-based vaccines are promising at present with their potential to provide a safe, cheap, and easy vaccine. Since RNA-based vaccines do not contain any whole virus in the way live-attenuated vaccines do, there’s no risk that a vaccine could inadvertently infect somebody with the virus. Studies have also shown nucleic acid vaccines to be safe and tolerable (Ferraro, et al., 2011). Nucleic acid vaccines can also be produced easily (Ulmer, Mason, Geall, & Mandl, 2012) and don’t require large quantities of the virus to be farmed.


However, comprehensive testing is still required to confirm the efficacy of current RNA vaccine candidates and ensure that the widespread distribution of a vaccine will slow or stop the spread of the virus. At the time of writing, even the most advanced vaccine candidates are still in phase III testing (Milken Institute, 2020). This stage is crucial, and rushing this stage or skipping it completely, as was done with Russia’s ‘Sputnik V’ vaccine, could have significant consequences from health impacts to diminished public confidence in vaccinations (Caddy, 2020). That said, the rapid development of RNA vaccines in response to COVID means that the first candidates should complete phase III testing and the initial batch of vaccines should become available in 2021 (Hogan, et al., 2020).


However, the challenge of getting a vaccine through testing is mirrored by the challenge of distributing a vaccine after testing. It’s estimated that 60-70% of a population will require accination for the population to have herd immunity (E.Randolph & B.Barreiro, 2020). Of course, producing a vaccine on a scale anywhere large enough to meet the demand is going to be difficult whilst we still don’t know which vaccines will pass phase III testing.


Furthermore, in the likely case that one or more RNA vaccines go into production, the new technology has many hurdles in getting the vaccines out to those who need them. RNA itself is inherently unstable and heat sensitive, and current vaccine candidates may need to be stored at temperatures as low as -20°C to -70°C (Zhang, 2020). These temperatures would need to be maintained during both transportation and storage. This may be possible for large hospitals, but for smaller health centres and remote areas it will be difficult, and in some areas of the world impossible. What’s more, for the sake of speed current RNA vaccines are being formulated in large multi-dose batches and without preservatives, something doctors aren’t used to (Zhang, 2020). This, as well as the short shelf life and the fact that (Zhang, 2020) means that doctors will need to efficiently deliver hundreds of vaccinations in a limited time frame. To further complicate things, several vaccine candidates will require multiple doses(Zhang, 2020). This multiplies the logistical nightmare, as health centres will need to ensure that they have vaccines ready for people’s subsequent doses lest the first becomes redundant, and if multiple vaccines come onto the market they will need to track which one people have had, as mixing vaccines may not provide full immunity.


These are serious challenges that still need to be faced, although progress is already being made in tandem with vaccine development. Estimates suggest that even after a vaccine is found, it may take six months to a year until enough people are vaccinated (Gallagher, 2020). We’re hopeful that it may only be a matter of months until the first vaccines come into use, and even an imperfect vaccine may have a significant benefit to public health (Elsland & Johns, 2020). However, logistical considerations and lack of suitable production capacity mean for the foreseeable future it’s likely that the vaccine will be limited to front liners. In this situation, the most crucial thing is to do whatever we can to limit the spread of the virus, minimise the impact as much as we can, and look forward to a time when this pandemic is behind us.

 

Caddy, S. (2020, August 24). Russian SARS-CoV-2vaccine. BMJ, 370. doi:https://doi.org/10.1136/bmj.m3270


Callaway, E. (2020, April 28). The race for coronavirus vaccines: a graphical guide. nature(580), 576-577. doi:https://doi.org/10.1038/d41586-020-01221-y


E.Randolph, H., & B.Barreiro, L. (2020, May 19). Herd Immunity: Understanding COVID-19. Immunity, 52(5), 737-741. doi:https://doi.org/10.1016/j.immuni.2020.04.012


Elsland, D. S., & Johns, S. (2020, September 25). COVID-19 vaccine may not need to be fully effective to benefit public health. Retrieved from Imperial College London: https://www.imperial.ac.uk/news/205153/covid-19-vaccine -need-fully-effective-benefit/


Ferraro, B., Morrow, M. P., Hutnick, N. A., Shin, T. H., Lucke, C. E., & Weiner, D. B. (2011, August 1). Clinical Applications of DNA Vaccines: Current Progress. Clinical Infectious Diseases, 53(3), 296-302. doi:https://doi.org/10.1093/cid/cir334


Gallagher, J. (2020, October 1). Covid: Vaccine will ‘not return life to normal in spring’. Retrieved from BBC News: https://www.bbc.co.uk/news/health-54371559


Hogan, A. B., Winskill, P., Watson, O. J., Walker, P. G., Whittaker, C., Baguelin, M., . . . al., e. (2020). Modelling the allocation and impact of a COVID-19 vaccine. London: Imperial College London. doi:https://doi.org/10.25561/82822


Johns, S. (2020). Robin Shattock tells MEPs of ‘promising’ vaccine progress. London: Imperial College London. Retrieved October 21, 2020, from https://www.imperial.ac.uk/news/204773/robin-shattock-tells-meps-promising-vaccine/


Milken Institute. (2020, October 16). COVID-19 TREATMENT AND VACCINE TRACKER. Retrieved October 18, 2020, from Milken Institute: https://covid-19tracker.milkeninstitute.org/


Moderna Inc. (2020). Moderna’s Work on a COVID-19 Vaccine Candidate. Retrieved October 21, 2020, from Moderna: https://www.modernatx.com/modernas-work-potential-vaccine-against-covid-19


Ulmer, J. B., Mason, P. W., Geall, A., & Mandl, C. W. (2012, June 22). RNA-based vaccines. Vaccine, 30(30), 4414-4418. doi:https://doi.org/10.1016/j.vaccine.2012.04.060


Zhang, S. (2020, September 28). Vaccine Chaos is Looming. Retrieved from The Atlantic: https://www. theatlantic.com/health/archive/2020/09/covid-19-most-complicated-vaccine-campaign-ever/616521/


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