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The first batch of COVID vaccines touched down in South Africa in February 2021. Health workers were the first to get a jab under the Sisonke study. But even before the country had bought any jabs, our reporters were writing about the logistics and the politics of the project. If you want to know how well the vaccines work, how the different jabs compare or what it takes to create a vaccine from research, to regulation, to rollout, you’re at the right place.

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COVID vaccines 101: Breaking down the good, the bad, and the promise of the frontrunners

With hundreds of potential COVID vaccine candidates being tested around the world, here’s a quick guide to which ones you should keep an eye on — and when we could see results.

As of 9 September, 180 COVID-19 vaccine candidates are being tested around the world, according to the World Health Organisation — but only 35 of those have managed to make it out of the lab into human trials. And of the candidates being tested on people, only about a quarter — 9 — have made it to phase three trials, which is the stage during which the vaccine is being tested on a large number of people for efficacy and safety.

Trials traditionally go through several stages, beginning with laboratory tests and animal studies, to ensure that they are safe and demonstrate some benefit. If positive results are obtained during this stage, by means of an immune response against the virus, the research can then progress to human trials, which occur in three phases. Each stage gets progressively bigger in size and finetunes details such as the correct dosage required, with phase three being the final stage before seeking regulatory approval if the vaccine turns out to be effective.

So which vaccine trials should you be watching and when are we likely to see their results?

We break down five of the phase two and three frontrunners.

1. University of Oxford/AstraZeneca

Vaccine name: AZD1222 / ChAdOx1 nCoV-19

What type of vaccine is it?

The vaccine is made out of a weakened version of a chimp adenovirus, which is a type of common cold virus. This kind of vaccine is known as a viral vector, or a “trojan horse”, where an inactivated virus is used as a carrier to help prime your immune system to respond to another virus. In this case, the adenovirus has been genetically altered to help sneak the spike proteins on the new coronavirus into your body. The idea is that by exposing your immune system to this non-harmful adenovirus, if you get infected with SARS-CoV-2 (the virus that causes COVID-19), your body will recognise its structure and destroy the virus.

How far along is the trial?

Phase three trials are underway in the United Kingdom, the United States and Brazil, and a merged phase 1 and 2 trial is being conducted in South Africa. The trial was paused on 9 September around the world for safety reasons. The UK arm resumed on 12 September, the Brazil study on September 14,  and the South African arm resumed on Tuesday with the US likely to follow. Early results for the South African arm of the study were expected this year, with the promise of rolling the jab out as soon as 2021, but will now be delayed because of the interruption of the trial, researchers say.

Pros: Since it doesn’t require any new technology, this type of vaccine can be produced alongside more traditional vaccines, which, like the Oxford/AstraZeneca vaccine, use inactivated viruses. This means that companies already manufacturing vaccines would easily be able to make the Oxford/AstraZeneca vaccine and produce a large number of doses within a fairly short time span.

Cons: Although the idea of viral vector-based vaccines is not new, to date one using an adenovirus has never been licensed or used in humans. Early data on the vaccine, published in a May preprint on BioRxiv, showed that the jab did not prevent monkeys from getting infected with the virus, but instead prevented severe lung damage and offered protection from coronavirus-related pneumonia. In short: the vaccine is unlikely to prevent infection with SARS-CoV-2, but will rather protect infected people from falling seriously ill with the virus.

2. Johnson & Johnson/Janssen

Vaccine name: Ad26SARS-CoV-2

What type of vaccine is it?

Like the Oxford/AstraZeneca jab, this is a viral vector vaccine. But the Johnson & Johnson vaccine uses a human adenovirus —  a strain of the common cold virus known as Ad26 — instead of a chimp adenovirus. As with the Oxford/AstraZeneca shot, the adenovirus is used to get your body to produce an immune response to the spike proteins present on SARS-CoV-2. The Adeno 26 virus is also used as a  viral vector for an HIV vaccine that Johnson & Johnson and partners are currently testing in South Africa and elsewhere.

How far along is the trial?

Merged phase one and two trials are being conducted in the United States and Belgium. These are smaller scale studies in around 1 000 participants to test the safety profile of the vaccine candidate and to establish if there’s any indication that it could offer protection from SARS-CoV-2. Further phase two studies are also planned for the Netherlands, Spain and Germany. Phase three trials are expected to start in the US and other countries this month, depending on the results from the phase one study and regulatory approval, with South Africa as one of the participating sites. A separate phase three study will be conducted in the United Kingdom testing a two-dose regimen of the shot.

Pros: Data published in Nature shows that a single shot was able to protect five out of six monkeys from getting infected with SARS-CoV-2 and resulted in the production of neutralising antibodies, which protect our bodies’ cells from getting infected. A similar protective effect was produced when the vaccine was tested in hamsters. A comparable Ebola vaccine was given European regulatory approval in May and the same technology has been used in the development of vaccine candidates for HIV and the Zika virus.

Cons: Viral vector-based vaccines tend to use an uncommon virus as the carrier to reduce the likelihood that people who get the vaccine have already been exposed to the virus. A potential downside to using common cold viruses as vectors, in particular the Ad26 strain that the Johnson & Johnson vaccine candidate is using, is that there is a chance that people have already developed immunity to it. In such cases, our bodies may destroy the vector before it’s able to produce a response to the coronavirus that is hidden inside the vector.

3. Novavax

Vaccine name: NVX-CoV2373

What type of vaccine is it?

Novavax, an American biotech company, designed a recombinant nanoparticle vaccine. This involves sequencing the SARS-CoV-2 virus to find the most common form of the spike protein present on the virus. Unlike viral vector vaccines, where a protein is hidden inside another virus, the spike proteins in recombinant nanoparticle vaccines are attached to the surface of a very small particle, called a nanoparticle. The nanoparticle is combined with an adjuvant, a substance which creates longer-lasting immunity in the vaccine.

How far along is the trial?

The initial phase one trial took place in Australia. In August, phase two trials started in  Australia, the United States and South Africa. Three thousand volunteers will participate in the South African arm of the trial — the study will test the safety and efficacy of the vaccine in both HIV-positive and HIV-negative people. Phase three trials in the United Kingdom are expected to begin in the third quarter of 2020.

Pros: The phase one trial showed promising results, published in the New England Journal of Medicine in September: no serious safety issues were reported and the vaccine resulted in 134 recipients developing high levels of neutralising antibodies. Recombinant nanoparticle vaccines produce stronger immune responses than viral vector vaccines, as shown by the high concentrations of neutralising antibodies that study participants developed in the phase one trial. The same technology is used in HPV, hepatitis B and shingles vaccines — these inoculations have demonstrated that recombinant nanoparticle vaccines are safe to use.

Cons: Although nanoparticle vaccines produce strong immunity responses, few companies are able to produce them because they haven’t yet acquired the technology to do so.

4. Moderna/National Institute of Allergy and Infectious Diseases

Vaccine name: mRNA-1273

What type of vaccine is it?

mRNA vaccines use pieces of man-made genetic material to instruct your body to produce proteins that can fight a particular virus. The type of genetic material such vaccines use is called messenger ribonucleic acid, or mRNA — mRNA delivers instructions to your cells to create the required viral protein that your body’s immune system will then use to fight the virus.

How far along is the trial?

Phase three trials began in July in the United States. Moderna has already committed to delivering 220 million doses to America, Europe and Japan. The American-based vaccine developer says it’s able to produce between 500 million to 1 billion shots per year and it will start rolling out the vaccine within the first half of 2021, if it is found to be effective and safe in time. In November, the biotech company announced that early data of the jab showed 94.5% efficacy. This was based off an analysis of 95 confirmed COVID-19 cases among participants which has not yet been published in a peer-reviewed scientific journal.

Pros: mRNA vaccines can be developed relatively fast and they’re cheap and easy to manufacture in large quantities. Low doses of such inoculations are needed for protection — a lower dose means that there is less need to ration the vaccine and more people can be reached.

Cons: The technology is new and no vaccines using mRNA messengers have been licensed for human use. There are also concerns about the natural instability of mRNA, with manufacturers needing to make specific adjustments to the genes in order to increase how long they last when placed into a therapeutic intervention like a vaccine. While ordinarily, mRNA vaccines tend to not be temperature sensitive, making them more accessible to countries unable to maintain a cold chain, COVID-19 mRNA vaccines like Moderna and Pfizer need to be stored at temperatures below 0 degrees celsius. In November, Moderna announced that new data showed their candidate could be kept between two and eight degrees Celsius — the temperature of a standard refrigerator — for 30 days. But it would still need to be kept at minus 20 degrees Celsius during transportation and long-term storage.

5. Pfizer/BioNTech

Vaccine name: BNT162

What type of vaccine is it? 

Like the Moderna vaccine, this jab uses pieces of man-made genetic material known as messenger ribonucleic acid, or mRNA, that instructs your body to produce proteins, in the form of antibodies and killer cells, to fight SARS-CoV-2.

How far along is the trial?

Pfizer/BioNTech’s candidate was initially the first to announce results from their trial in early November, showing 90% efficacy in protecting those who had not previously been infected with SARS-CoV-2. Further analysis in its phase three trial showed 95% efficacy in participants, regardless of whether or not they had been previously infected with the virus. The results have not yet been published in a peer-reviewed scientific journal. As part of an expedited development process, this American-German partnership is running phase two and three trials simultaneously, both of which began in July. Countries in which the trial is being conducted include the United States, Germany, Brazil, and Argentina. The pharmaceutical company hopes to get regulatory approval and have 100 million doses manufactured by the end of the year, with over 1 billion shots ready by the end of 2021. In September, Pfizer agreed to provide the European Commission with 200 million doses from the end of this year, should the candidate be successful in trials.

Pros: Preclinical trials in animals showed that the vaccine was able to prevent lung damage in monkeys and resulted in the production of antibodies in mice, according to a September preprint on BioRxiv. The data was published in a preprint in medRxiv.  As with the Moderna vaccine candidate, which uses the same technology, the Pfizer/BioNTech vaccine is easy and cheap to manufacture and design.

Cons: As with the Moderna vaccine, the main downside is that mRNA technology is new and there is therefore no real-life experience with it, as no such vaccines have been licensed for human use. There are also concerns about the natural instability of mRNA vaccines.

Want to know about some other vaccines in the pipeline? Check out this cheat sheet from the AVAC.

[Updated 16:33 18 November 2020: This article was updated to reflect new data released about Pfizer/BioNTech COVID-19 vaccine candidate, which showed 95% efficacy.]

[Updated 13:21 17 November 2020: This article was updated to reflect new data released about both the Pfizer/BioNTech and Moderna COVID-19 vaccine candidates. Early data showed 90% efficacy in Pfizer’s jab and 94.5% efficacy in Moderna’s. Moderna also released new data showing their vaccine was found to be stable at lower temperatures.]

Aisha Abdool Karim was a senior health reporter at Bhekisisa from 2020 to 2022.