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Covid-19: the complicated process to make an effective vaccine

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“It's a race against the virus disappearing, and against time”

This was what Professor Adrian Hill, director of the university’s Jenner Institute, said to the Telegraph during an exclusive interview on the 23th of May. Professor Hill is leading the development of the potential vaccine ChAdOx1 nCoV-19, now known as AZD1222, together with Oxford Vaccine Group at the University of Oxford. This vaccine was developed by genetically modifying a virus that causes infections in chimpanzees, in order to weaken it so it doesn’t replicate in humans. Then, other genetic modifications have been made to make it produce a protein typical of the COVID-19 virus called the Spike protein, a surface protein that allows the virus to enter human cells. The AZD1222 vaccine should make the body recognise the Spike protein and start an immune response that stops the virus from entering human cells and therefore prevent infection.


In April the Oxford research group announced an 80% probability of success of the candidate vaccine, with the expectation to distribute about a million doses by September 2020 once they obtained the results of vaccine tests. This is months shorter than the official 12- to 18-month timeline quoted by experts around the world. However, nowadays, with the daily falling number of infected people in UK, there is actually a concern that the virus might disappear . Oxford researchers need thousands of people infected by Covid-19 to compare the number of infections in the control group with the number of infections in the vaccinated group to check if the vaccine is effective.


AZD1222 has already passed Phase 1 clinical trials that involved around 1,100 people (18-55 year old volunteers in good health) in a blinded study to test vaccine safety profile (to check it doesn’t induce adverse reactions) and its immune response induction. In this study volunteers were randomly assigned to two groups: one got AZD1222 vaccine, whilst the other was assigned a licensed vaccine against meningococcus, used as a “control” for comparison of side effects and immune response. To compare a vaccine’s positive and negative effects, you can’t just give the “control” group nothing - that wouldn’t present even minor vaccine side effects such as sore arm. This would let participants know who took the vaccine and who didn’t, which might influence their behaviour in the trial. That’s why the study is called a ‘blinded study’, it means none of the participants know what group they are in so they don’t affect the results by their preconceptions. Results on AZD1222 safety profile were positive: in fact, volunteers treated with AZD1222 had no critical side effects after vaccination, apart for temporary higher temperature, headache or sore arm. However, before starting human tests, the vaccine was tested on animals where it gave no satisfactory efficacy in inducing immune response – i.e. the vaccine didn’t protect them from infection. Also, some monkeys were all exposed to SARS-CoV-2 and then divided in two groups: the first was vaccinated with a single dose of AZD1222, while the other was not vaccinated. The study showed that the vaccination in the first group of monkeys prevented infections in their lungs – but in their noses there was as much virus as in unvaccinated monkeys. This means the vaccine can protect from pneumonia (the worst complication induced by the virus) but not prevent animals being infected and spread the virus, maybe because the administered dose of vaccine was not enough for the high dose of virus to which animals had been exposed. In this case, a second injection could increase the immunological response appreciably. Tests on animals are essential because they can give important predictions on humans tests results.



Once monkeys showed no safety concerns, Oxford Vaccine Group started recruiting for Phase II/III Clinical trials with 10 times the number of people to check effects both on children and adults and to assess how well the vaccine works to prevent people from becoming infected and unwell with COVID-19. If the vaccine proves to be successful, then the team will apply for "emergency use approval" to roll out the inoculation programme immediately. For this to be achieved its necessary that the rate of infection doesn’t fall too fast.

“How quickly we reach the numbers required will depend on the levels of virus transmission in the community. If transmission remains high, we may get enough data in a couple of months to see if the vaccine works, but if transmission levels drop, this could take up to 6 months” Professor Hill declared.


Who is supporting AZD1222’s development? After having received £20 million from the UK Government, the Jenner Institute and Oxford Vaccine Group announced at the end of April an agreement with the bio-pharmaceutical company AstraZeneca, headquartered in Cambridge, which is now responsible for development and worldwide manufacturing and distribution of the vaccine. In fact, at the same time as preparing for and conducting the first clinical trial, production of the vaccine is being scaled up ready for larger trials, and potentially, future deployment. The initial manufacturing method was designed by Dr. Alexander Douglas at Oxford, but the production needs to be massively scaled-up. AstraZeneca has secured total manufacturing capacity for one billion doses so far and will begin first deliveries in September 2020, firstly to UK citizens and then worldwide. Several parallel supply chains have been developed in the meantime, so to make vaccine available as soon as possible and to assure safe manufacturing processes. On the 21th of May AstraZeneca received more than 1 billion $ from the US Biomedical Advanced Research and Development Authority (BARDA) to develop, produce and distribute the vaccine. BARDA is a manufacturing specialised research centre itself, and represents a parallel production chain of thousands of AstraZeneca/Oxford vaccine, in order to control a safe manufacturing process. What is more, it is financing and supervising many other development projects worldwide in the fight against Covid-19 (such as Moderna and Janssen’s vaccines, both with positive Phase I clinical trials results). Another supply chain working in parallel with AstraZeneca on Oxford vaccine is set in IRBM company located in Pomezia, which has produced hundreds of vaccine doses already used in university tests.


It’s evident that huge international efforts are made to ensure scientific progress in public health. International discussion is also focused on the global welfare aspect:. AstraZeneca is progressing together with international organisations such as the Coalition for Epidemic Preparedness Innovations (CEPI), Gavi the Vaccine Alliance and the World Health Organisation (WHO), for the fair allocation and distribution of the potential vaccine around the world and is establishing discussions with governments around all the planet to increase access and launch production and distribution with Asian partners as the Serum Institute of India and others. Private investors are essential for the success of the project. Co-founders of CEPI are Bill & Melinda Gates, the couple who started the “Decade of Vaccine” together with WHO to finance and lead the discovery of new vaccines against future pandemics.


WHO has an incredible coordination role: it has established specific guidelines over vaccine development that must be followed by research centres to obtain reciprocal collaboration. In January the Organisation published its experts’ first criteria over vaccine mechanism of action, stating “Participants emphasized that vaccine antigens are expected to preferably target the nCoV Spike protein” (as we initially said the Oxford vaccine does). In April WHO declared in which modalities any collaborative company and institution should organise clinical trials of their candidate vaccines against COVID-19, so to gain an international coordination and to enabling assessment of whether any are appropriate to make global interventions that can influence the course of the pandemic.


Institutional collaborations are fundamental, now more than never before: even if in the worst scenario a Covid vaccine will not be approved, the process of fast-paced research and setting up operational supply chains will prepare us for any future pandemics. As Professor Sir John Bell, Professor of Medicine at Oxford University, said: The risk of new pandemics will always be with us and the new research centre will enhance the world’s preparedness and our speed of reaction the next time we face such a challenge.”

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Click here to find latest WHO updates on COVID-19 candidate vaccines.

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Š 2019 by Biology in Context. Images are from the Public Domain or created with Biorender.com. Website created with Wix.com

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