The working vaccine can just be announced in the coming weeks:...

Somewhere in the coming weeks it could just be that far: the announcement of the world’s first, real vaccine results, tested on a real population where the virus is circulating. The contenders in a row.

Ten vaccinated people – and at least five of them must be protected against the corona virus. While no one gets side effects that are more serious than a shivering feeling or some pain around the puncture site.

That is about the profile of a vaccine against corona, of which the first if all goes well will see the light of day in the coming months. Because at any time, a producer of one of the many vaccines currently being tested may come to the conclusion that his vaccine is ready for the market.

In a control group of people who received a placebo drug, so much more people became infected than in an vaccinated group, that the manufacturer declares the vaccine ‘effective’. The difference between these groups – ‘events’, according to vaccinologists – may already be the case with a few dozen cases. Then it is time for the next step and the manufacturer will apply for marketing authorization, with the medicines authority EMA in Europe or the FDA in America.

And yes, you read that first sentence correctly: although the vaccine must be safe, it does not immediately have to protect everyone. As long as it’s enough to get the virus on its feet. ‘Even if the vaccine is only 50 percent effective, you still have prevented half the disease and death. That is very good, ‘says Cécile van Els, immunologist at RIVM and professor of vaccinology at Utrecht University.

Moreover, says Van Els, the first vaccines are just the beginning. ‘Other vaccines are on the way, sometimes with completely new concepts. Vaccines that target several proteins of the virus, for example, or vaccines that you can administer as a nasal spray, ‘she says. Who knows, they might be better than the front runners. Although it is to be hoped that newcomers will be able to gain a foothold between the vaccines that are already available by then, says Van Els.

The world is already impatiently eager. For example, the construction of factories to produce the vaccines is in full swing, and the EMA is carrying out so-called ‘rolling reviews’ for some contenders, while the trial is still underway. Europe has already taken an option on a total of 1.3 billion doses from six contenders – we’ll discuss them on these pages, plus a few others.

Which vaccine has the best credentials? Nobody knows that at the moment. Because no matter how formidable vaccines sometimes fared in the first cautious human trials, the litmus trial remains the so-called ‘phase 3’ of the study, when they are tested for effectiveness for the first time in the ordinary world, where the real virus haunts – a baptism of fire currently undergoing 17 vaccines.

‘It is expected that some of them will reach the finish line. But products can still be lost, ‘says Van Els. “It’s a really exciting time now.”

1 | THE LEADER (AstraZeneca, University of Oxford)

What a luck. The University of Oxford was just working on a vaccine against the coronavirus that sometimes spreads from dromedaries to humans when the new corona virus emerged. As a result, the ‘Oxford vaccine’, as it is also called in the corridors, was the first to get off the starting blocks.

The vaccine was built by giving a chimpanzee cold virus the spines of the covid virus and is now being tested in Brazil, Great Britain, South Africa and the US. Experts were enthusiastic about the results of the first tests on small tufts of people: all participants developed antibodies against the virus and a ‘T-cell response’, a form of defense that is especially important in coronaviruses.

But don’t cheer too soon. On September 8, the study was temporarily halted in three countries after a female participant contracted a rare form of spinal cord infection. The results in monkeys are also not entirely favorable: the vaccinated monkeys became less ill but still produced virus. That would indicate a vaccine that does not fully protect.

2 | THE ICE CABIN (Pfizer, BioNTech)

Another quickie: the German BioNTech, which makes vaccines from ‘messenger RNA’. This is a hereditary molecule that causes body cells to grow the coronavirus protrusions from their outside. Long story short: the body sees the spines, is startled, and builds up resistance – never again.

When US President Donald Trump talked about the vaccine that would be available before Election Day, he was referring to this vaccine, as manufacturer Pfizer has already hinted that the vaccine could theoretically be ready for the market in October. It just has to work for a while, with the 43,000 Americans, Germans, Brazilians and Argentines on whom it is currently being tested.

In any case, the results in the preliminary phase were hopeful: vaccinated monkeys remained healthy, subjects developed an apparently fine arsenal of antibodies and T cells. The biggest drawback so far is that the vaccine has to be stored at minus 70 degrees. That makes such a vaccine less suitable for the interior of Africa or South America.

3 | NEÊRLANDS HOOP (Johnson & Johnson, Janssen)

Leiden biotech company Janssen quickly adapted its already completed Ebola vaccine to combat the new corona virus. Like the Oxford vaccine, it is based on a harmless virus, but with the characteristic spines of sars-cov-2.

In hamsters and rhesus monkeys and subsequently 796 human subjects, this gave such good results that Janssen was able to start his final exam earlier than expected, a large-scale ‘phase 3’ trial among 60,000 people in nine countries. Trump card of the vaccine: one shot seems enough to offer protection.

But Janssen is not there yet. On October 12, the trials were temporarily halted to investigate the case of a patient who developed a serious adverse reaction – which one is unknown. That is already a sensitive point with the Janssen vaccine: in the preliminary phase one test subject developed a high fever and another increased blood pressure.

4 | THE MIRACLE CHILD (Moderna)

Moderna appeared on the scene with spectacle: in 2018, the newcomer raised a record amount of 621 million dollars (525 million euros) when entering the stock exchange. Not bad for a biotech company that has not yet launched any medicine on the market.

Maybe that will change this year. Moderna (the somewhat old-fashioned name refers to the messenger molecule RNA, or mRNA) wants to activate the immune system with RNA strands wrapped in fat vesicles, which, like the Pfizer vaccine, grow virus spines on cells.

Test now. The preliminary investigation was a bit tumultuous after the dosage turned out to be too high and a volunteer was temporarily hospitalized, but that bump thinks Moderna has ironed out. Perhaps the biggest problem is price. Moderna says it asks about 60 euros per vaccination of two injections, considerably more than other companies.

5 | THE SUSPECTOR (CureVac)

One billion dollars. This is how much President Trump would have done in March to bring the German company CureVac from Tübingen to the US, in a stunt that was interpreted in Europe as pure hostility. After all, Trump’s condition would be that CureVac’s vaccine would only be destined for the American market.

Use of Trump’s attempt to pick up: an (yet again) mRNA vaccine that gives body cells around the puncture site a coronavirus-like appearance, after which the immune system takes action. But although the company has also stolen the heart of Chancellor Angela Merkel – the Reichstag transferred a 250 million euros subsidy to CureVac last month – no test results are yet known.

6 | THE CLASSIC (Sanofi and GSK)

The disadvantage of the European vaccine orders, according to immunologist Cécile van Els, among others: they are a bit one-sided. After all, we now have three RNA vaccines that give cells corona protrusions and two vaccines from the ‘dressed cold viruses’ category. While both concepts are quite new in the vaccine world.

No, then the French concern Sanofi and the British pharmaceutical company GSK, two rock-solid multinationals from the Old World. The two veterans test a so-called ‘subunit vaccine’, according to the tried-and-tested recipe of the trusted flu shot: inject the loose spines of a coronavirus into the patient, and let the immune response begin. ‘Hopefully one such protein is enough,’ says Van Els.

Patient results are not yet available, and it is in any case relatively late: it is not until next summer that they expect to be able to apply for market approval. Another disadvantage is that one needs an ‘adjuvant’, an adjuvant that shakes up the immune system even more. And the adjuvant in question is suspected of causing hundreds of cases of sleeping sickness, narcolepsy in 2009.

7 | THE CREATOR (Gamaleya)

The world will know that Vladimir Putin’s Russia has the world’s first registered corona vaccine. ‘A well-tested technology with substantiated long-term safety’, can be read on the official website of the Russian vaccine. Above that, the name of the vaccine that Putin suddenly approved on August 11: ‘Sputnik V’. A reference to the 1951 artificial moon, the other time Russia outdid the rest of the world.

But it is precisely that ‘well-tested’ that is quite lacking. The vaccine has only been officially tested on a few hundred people, including employees of the Moscow Gamaleya Institute where it was developed itself. And when the world community saw the results of the first tests in September, after much insistence, they turned out to be downright suspicious: the graphs sometimes seemed carelessly copied from one place to another.

A lot of politics, little science, according to vaccinologists. ‘Even though it is independent of the question whether the concept can be successful’, says immunologist Van Els. ‘After all, the Russians use the same principle as the Oxford vaccine, or Janssen’s vaccine.’

But without solid figures: you just don’t know.

8 | THE CARE CHILD (CanSino)

And then there is that other vaccine that has already received preliminary approval: the vaccine from the Chinese company CanSino. It has been used to vaccinate Chinese soldiers against corona since June.

Yet the vaccine has struggled with a persistent problem from the start: it does not work well for many people. The vaccine is built around an existing cold virus, ‘adenovirus 5’. Many people already have resistance to this virus – with the result that they also resist the vaccine, as it turned out during the first patient trials. This is annoying, because for people for whom the vaccine does work, it gives hopeful results.

There is another disadvantage for Europe: China is not very inclined to sell the vaccine outside Asia. Only Russia, Saudi Arabia and Pakistan, where the vaccine is being tested, are eligible. And even that is uncertain: a collaboration with Canada was canceled at the last minute, because the Chinese customs suddenly refused to send the vaccines to Canada.

9 | DE SENIORENPRIK (Novavax)

Europe is still in talks with the American company Novavax, which has been working on a flu shot for the elderly for some time. But it is also possible with corona, Novavax thinks. The vaccine with which they want to do this: a mix of corona proteins glued together, with a special adjuvant based on vegetable soaps called saponins.

In the first trials, this yielded excellent results: volunteers received antibodies and a good T cell response, with only minor side effects. The large-scale ‘phase 3’ investigation is now underway and will probably last until the end of this year.

It just has to work. Novavax had a traumatic experience with its vaccine ResVax against the RS virus, also a respiratory virus. The vaccine achieved good results in the preliminary studies, but turned out not to work in the third phase, even after adjusting the dose. That shows how wrong things can go with a ‘promising’ vaccine just before the finish line.

Sources: Royal Dutch Association for Microbiology, STAT, In the Pipeline, Fierce Pharma, Biotech Express, BioPharma Dive.