Has COVID Accelerated the Course of Vaccine Development? HARRIET

HAS THE COVID-19 PANDEMIC AFFECTED VACCINE DEVELOPMENT NOW AND IN THE FUTURE?

By Harriet

Virology has never been reported on as frequently or as in depth as it had been since the start of the SARS-CoV-2 pandemic. There also seems to have been a greater rate of development of vaccines and technology surrounding vaccination during and due to the pandemic.

The truth is, before the rise of SARS-CoV-2, we already knew quite a lot about coronavirus, how they are structured and how to mitigate them because of the previous SARS and MERS epidemics. This means that as soon as the emerging virus was identified to be a coronavirus, no one was particularly surprised as there had been two epidemics of coronavirus in the past twenty years. Over the course of the pandemic, two novel forms of vaccines have been approved to add to the three previous forms of vaccination. There was also a new parallel development scheme created whereby the vaccine was being produced as testing was being done. The previous forms of vaccination are:

INACTIVATED VACCINE

This is when a killed version of the virus by chemical treatment is used as inactivatedvaccines don’t have ability to interact with cells or produce proteins which therefore does not causethe patient’s body any harm. However, if the immune system of the individual is exposed to enough units of the killed pathogen, an immune response can be induced. This, however, will be weak andwill need ‘booster’ vaccinations to cause a sufficiently protective immune response for when the wild virus enters the individual’s body. Examples of this type of vaccine are the polio vaccination as well as some more topical COVID-19 vaccines such as Covaxin, produced by an Indian company, Bharat Biotech. It has an efficacy of 78% against symptomatic patients and a 64% efficacy against asymptomatic patients. This type of vaccination hadn’t been changed or developed over the course of the pandemic.

LIVE ATTENUATED VACCINE

This is the original form of vaccination. This form was used 300 years ago by Edward Jennerto vaccinate the public against smallpox. The vaccine contains a weakened version of the pathogen which, once injected, produces weakened versions of the pathogenic proteins, training the immune system for when the virus enters the body wild. This causes a longer lasting immune defence than the inactivated vaccines, thus needing few follow up vaccinations. However, live attenuated vaccines can cause mild disease, all be it weakened. Protein is being produced thus immunodeficient patients may need to consult their General Practitioner before receiving the vaccine as it can cause more severe and longer lasting damage. An example is the MMR vaccine which is administered to babies. This type of vaccine has been totally unaffected by the pandemic as there has been no live attenuated COVID-19 vaccinations, thus causing no development or change to the vaccine or how it is produced.

SUBUNIT/RECOMBINANT/PROTEIN SUBUNIT VACCINES

These vaccines can, but don’t always, contain a chemical called an adjuvant. This stimulates the immune system causing a more effective immune response. An example is AS04 in an HPV vaccine called Cervarix. It is made up of monophosphoryl lipid A and Aluminium salt. Subunit vaccines take the genetic information of one appropriate protein, usually the spikeprotein, and produce it using an alternative method using molecular biology techniques. This is then injected into the body. As there are only fragments of the pathogen entering the body, not the whole virus, the fragments are rendered harmless so the immune response is still triggered, thus still developing an immune response against the pathogen. This also makes the vaccine very safe, allowing immunodeficient patients to have a vaccine without any problems. Examples include the vaccine against hepatitis B. There are many COVID-19 vaccines using this technique, the most popular being Nuvaxovid (approved in 36 countries including the United Kingdom. Vaccine structure or development has not been affected by the COVID-19 pandemic.although many types of subunit vaccinations have been made for sars-cov-2, very few have been approved or been effective.

The two types of vaccine that were most recently WHO approved are:

MRNA VACCINE

Research into mRNA vaccines started in 1990 and the first study was published in 1992 showing that encoding mRNA instructions for a therapeutic protein improved patient’s response to the virus. By 2015, the current model of modified-nucleoside mRNA-LNP vaccines had been created. The COVID-19 PfizerBioNTech Comirnaty vaccine was the first ever mRNA vaccine to be approved and the second was the Moderna spikevax vaccine. However, as seen in the brief history of this type of vaccine, the use of this type of vaccine was well underway regardless of the COVID-19 pandemic. The vaccine works by encoding a protein, again usually the spike in the case of SARSCoV-2, in some mRNA.This is a form of RNA that encodes the formula for proteins, thus can harness the host’s cells to produce the protein for which the immune system will develop its response against.The mRNA itself contains modified nucleosides because usually our cells don’t let mRNA from outside the cell into the cell,unless something has gone very wrong and thusthe cell will recognise the foreign mRNA and send off danger signals causing them to become inflamed.The modified nucleosides code instructions to tell the cell how to produce the required protein which will no longer be foreign to the cell. For example, Uridine is one of the conventionalbuilding blocks of mRNA setting off danger signals and s combatted using pseudo-uridine, a modified nucleoside, which is a natural variation of uridine and can be found in cells in excessnaturally. This is safe because it is degraded using normal pathways in our body so it wont causeside effects after being administered in the modified mRNA vaccine. mRNA is also unstable and is quickly degraded by RNA degrading enzymes, RNases. RNA is also large and difficult to get into the cell in order to start protein synthesis. This is done throughplacing the mRNA into protective Lipid nano particles (LNPs). These protect the mRNA from the RNases and allow it to enter the cell safely and efficiently, leaving the mRNA unaffected.

REPLICATING-DEFICIENT VIRAL VECTOR VACCINE

This is a technique that has been around for a long time as it dates back to the 1970s whengamma-retrovirus was able to acquire cellular genes. Adenovirus was first used as a vector in the 1980s showing promise for gene therapy to correct genetic mutations.The viral vector vaccines involves putting the genetic material into the non-replicating vector thus becoming a viral vector. This is then injected into the body where the vial vector infects the body’s cells where the expressed protein’s DNA is translated using the cells RNA polymerase (enzyme) into mRNA and then uses this type of cell to produce the desired protein, triggering animmune response. The first replicating-deficient viral vector vaccine to be approved in the UK was the Oxford/ AstraZenica vaccine, followed by Johnson&Johnson and Sputnik V vaccines.

This has allowed for vaccines to be administered as soon as trials have been completed and passed.This has allowed for efficient and safe delivery of vaccines. It is important to note that just because the process of vaccine development had been accelerated, it doesn’t mean that it is any less thorough or any less valid. Vaccine production had never had to be this drastic before, and thus its limits have never been tested on this scale. The faster development has allowed for further pandemic planning to be more effective. An example of this is that the Defense Advanced ResearchProject Agency (DARPA), an area of the USAs department of defense, is starting an initiative todevelop an improved approach to treat and stop future pandemics in sixty days. This is done through using mRNA technology to encode the antibody proteins needed to protect a person from the emerging pathogen. This won’t be a long term solution, but an initial attempt at slowing the spread of the emerging pathogen. This production plan differs from the normal schedule as vaccines are normally vigorously tested before mass production, thus taking a much longer time to administer the new vaccine to the public. Both of these types of vaccines have been in the making for quite some time and were already in the stages of creating vaccines for other viruses such as Ebola and Zika. This leads me to believe that the pandemic may not have accelerated approval because both forms of vaccine were in the processed to be approved anyway. It is also my belief that without the development of vaccines such as these, the pandemic will have played out differently especially in the latter stages. This is because the technology is modern, quicker and relatively easy to manipulate for other viruses thus developing a vaccine quicker and more accurately than previous methods. Out of the two new techniques, I believe that modified-nucleoside mRNALNP vaccines have the largest scope for further development. This is because of their simple design, quick production and their manipulative qualities,for example, the idea of harnessing new CRISPR technology. This ability to change the DNA of a cell in order to treat genetic defects such as sickle cell anaemiais revolutionary and still a blossoming technology. By using mRNA-LNPs to encode CRISPR proteins to directly alter the genes of patients could be a cheaper and more efficient way of administering them. This has infinite possibilities which is both incredible and scary, but by harnessing both techniques you could have the power to do anything with the genes in our cells. In conclusion, the COVID-19 pandemic has affected vaccine developmentbut not to the extent as thought by the general public. I think that the greatest difference it had made is thrusting virology into the media and allowing the scientists who were never going to be known by the vast majority of the public now to be household names. It has also given virology the attention and the appreciation that it needs and deserves.

REFERENCES

https://covid19.trackvaccines.org/vaccines/25/https://news.sky.com/story/covid-19-johnson-johnsonsingle-dose-vaccine-approved-for-use-in-the-uk-12319122 https://vk.ovg.ox.ac.uk/vk/covid-19-vaccines www.edx.org/course/the-covid-19-pandemic-and-the-use-of-mrna-vaccines?index=product&queryID= 22e418c3af689a33b62d7d77c7118ea9&position=1 NewScientist, 14 August 2021, ‘What we know so far’