Clinical Trials – How to test vaccines

The UK has entered the clinical trial race to find a vaccine against Covid-19. I’ve previously written a post about vaccines but not how they are tested prior to distribution amongst the general public. Here we will explore clinical trials and the type of vaccination the UK is currently testing.

As we head into another week of lockdown in the UK, it is promising to hear that clinical trials for a vaccine candidate, developed at the University of Oxford in conjunction with other research institutions, have begun. When discussing this, I realised I didn’t know how new vaccines are tested. For most medication, standard clinical trials include 3 main phases, evaluating the medical, surgical, or behavioural intervention being trialled. Here, clinical trials are used to determine if the new method or treatment is more or less effective than current ones, or if side effects are more or less harmful than those of current treatments. Drugs (or treatments) have to be better than what is currently on offer before they are given the green light.

Phase I trials typically test the new treatment on a small group of healthy people (~20-80) to judge safety, side effects and correct dosage, whilst Phase II trials use more people (~100-300) determining the effectiveness of the treatment. This stage of trials can take years and usually includes people who have the disease or condition being targeted. Phase III trials look at safety and effectiveness in different populations, and dosages in combination with other drugs (i.e. any bad interactions), testing against thousands of participants. This phase can be a blind trial, where the doctors and patients don’t know if they’re receiving the real drug or a placebo. After this, the drug/treatment will be approved or denied by the FDA (Food and Drug Administration) and/or MHRA (Medicines and Healthcare products Regulatory Agency, in the UK) for widespread use; this is when Phase IV trials start. The drug is now in widespread use but still being monitored for side effects which may not show themselves for a long time etc. clinical trials

A vaccine however isn’t the same as a tablet; they need to make the body produce an immune response to create antibodies against a viral infection. How can scientists test for this? Do they have to expose individuals to the virus eventually? It is important to understand the clinical trials stages so we know whether or not a vaccine is effective and safe. Phase I are again small scale and look at safety in humans, however vaccine trials are at this stage, assessing the immune response which the vaccine invokes. Phase II is a larger trial determining the vaccine’s response to artificial infection, whilst monitoring side effects. Phase III is a larger trial still, mimicking natural disease conditions across numerous sites over a set period of time. Only after proving its worth through these trials can a vaccine be authorised. Long term immune response (efficacy) is monitored after general release (Phase IV).

The first Covid-19 vaccine trials were due to start in the UK on Thursday 23rd April (2020), recruiting up to 510 healthy volunteers between the ages of 18-55 from a few locations in the UK (Bristol, Thames Valley, Southampton, and Greater London). If you meet the criteria, and live in any of those areas, you can volunteer for the trial HERE. The first stage of this trial will give half the participants the Covid-19 vaccine, whilst the other half receive a “control” vaccine which protects against meningitis and sepsis. This stage should last 6 months, testing antibody production. There are between 80-100 promising vaccine candidates in development across the Globe, so I won’t go into huge detail as to how this first UK vaccine was developed as many have taken different approaches to vaccine generation, but this is the general picture:

The Oxford University team are using a weakened chimpanzee adenovirus (common cold) vector (i.e. something which can carry foreign DNA into the body), to generate a strong immune response from just one dose. An added bonus is that the adenovirus is not a replicating virus so cannot cause an ongoing infection, making it safer for children, the elderly and anyone with a pre-existing condition (e.g. diabetes). These vectors will contain DNA for the coronavirus surface “spike-proteins“. Studies so far suggest these proteins are a good target of successful vaccinations. Once in the body, these spike-proteins should be produced without causing disease within the individual. However, their presence will induce an immune response as the proteins are foreign to the body, and should therefore create antibodies to be stored for later use, if the coronavirus reaches that individual.  covidvaccine

Such chimpanzee adenoviral vectors are well-studied in vaccines, and have been used safely in thousands of people from 1 week to 90 years of age, in vaccines targeting over 10 different diseases. Prof. Gilbert, who leads the Oxford based research group, has previously developed a vaccine for another human coronavirus disease, the Middle East Respiratory Syndrome (MERS), which has shown promise in early clinical trials. Although these steps are promising and on a drastically shortened time frame, compared to the usual 10-20 years in development and testing, a ready-to-use vaccine is still a while off. The earliest predictions for completion are the middle of 2021, but even this is a best case scenario. I hope to write more in the coming weeks about the different types of vaccines under development to show the various methods being trialled, and how we are still unsure of the best method. However, as with last week’s ventilator post, it is phenomenal to see research groups which would usually be competing, coming together to tackle this Global issue, resulting in this unprecedented speedy response.

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