Coronavirus vaccine trials have their first results – but their promise is still unclear

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PPE nurse gives flu shot at church in Buenos Aires, Argentina

Coronavirus vaccines are being tested in humans and animals.Credit: Juan Ignacio Roncoroni / EPA-EFE / Shutterstock

As coronavirus vaccines progress during development, scientists are getting their first glimpse of data that suggests the effectiveness of different vaccines. So far, the picture has been blurred.

US biotech company Moderna released the first data from a human trial yesterday: Its COVID-19 vaccine elicited an immune response in humans and protected mice from SARS-CoV coronavirus lung infections -2. The results – announced in a press release from the Cambridge, Massachusetts-based company – were widely interpreted as positive and pushed the stock markets higher. But some scientists say that because the data is not published, they lack the details necessary to properly assess these claims.

Testing of other accelerated monkey vaccines has prevented lung infections in animals exposed to SARS-CoV-2 – but not in other parts of the body. One – a vaccine under development at the University of Oxford, UK, which is also being tested on humans – protected six monkeys from pneumonia, but their noses contained as much viruses than unvaccinated animals, researchers reported.1 last week in a bioRxiv preprint. A Chinese group has reported similar warnings about the first animal testing of its vaccine this month.3.

Despite these uncertainties, the three teams are continuing clinical trials. These early studies are primarily intended to test safety, but larger clinical trials to determine if vaccines can actually protect humans from COVID-19 could signal as early as this summer.

However, the first data offer clues to how vaccines against coronaviruses could generate a strong immune response. Scientists say animal data will be crucial to understanding how coronavirus vaccines work, so that the most promising candidates can be quickly identified and subsequently improved. “We could have useful vaccines in people in the clinic within 12 or 18 months,” said Dave O’Conner, virologist at the University of Wisconsin-Madison. “But we will have to improve them to develop second and third generation vaccines. “

Immune response

The Moderna vaccine, which is under development with the United States National Institute of Allergy and Infectious Diseases (NIAID) in Bethesda, Maryland, began human safety testing in March. The vaccine consists of mRNA instructions for the advanced protein of the coronavirus; human cells produce the foreign protein, alerting the immune system. Although easy and safe to develop, these RNA-based vaccines have yet to be licensed worldwide.

In its press release, the company said that 45 study participants who had received two doses of the vaccine developed a strong immune response to the virus: they measured antibodies recognizing the virus in 25 participants. These antibody levels were similar to or higher than those found in the blood of people who recovered from COVID-19.

Tal Zaks, chief medical officer of Moderna, said in a presentation to investors that these levels of antibodies augur well for the vaccine that prevents infection. “If you get to the level of people who have had the disease, that should be enough,” said Zaks.

But it is not at all clear if the answers are adequate to protect people from infection because the data is not published, said Peter Hotez, a vaccine specialist at Baylor College of Medicine in Dallas. “I am not convinced that this is really a positive result,” said Hotez. It points to a bioRxiv preprint of May 152 this revealed that most people who recovered from COVID-19 without hospitalization did not produce high levels of “neutralizing antibodies”, which stop the virus from infecting cells. Moderna measured these potent antibodies in eight participants and found that their levels were similar to those of the recovered patients.

Hotez also has doubts about the first results from the Oxford team, which revealed that the monkeys produced modest levels of neutralizing antibodies after receiving a dose of vaccine (the same diet that is tested in human trials) . “It seems these numbers have to be considerably higher to provide protection,” says Hotez. The vaccine is made up of a chimpanzee virus that has been genetically engineered to produce a coronavirus protein.

He says that the vaccine developed by Sinovac Biotech in Beijing seems to have elicited a more promising antibody response in macaques having received three doses, according to the data presented.3 in a May 5 Science paper. This vaccine is made up of chemically inactivated SARS-CoV-2 particles.

No one yet knows the precise nature of the immune response that protects people from COVID-19, and the levels of neutralizing antibodies produced by monkeys may be good enough to protect people from infection, says Michael Diamond, viral immunologist at the University of Washington in St. Louis, which is a member of the Moderna scientific advisory committee. Otherwise, a second blow would likely propel them to much higher levels. “What we don’t know is how long they will last,” he adds.

Animal studies

Even more questions hang over experiments showing that vaccines can protect animals from infection. Moderna said his vaccine, which has also been tested in mice, has stopped viral replication in the animals’ lungs. Rodents were infected with a version of the virus that has been genetically engineered to allow infection of mouse cells, which are generally not susceptible to SARS-CoV-2, according to Zaks’ presentation. But viruses are mutated into the protein that most vaccines, including Moderna, use to boost the immune system, which could affect animals’ response to infection.

Oxford monkeys did not develop any signs of pneumonia after infection. But their noses had as much SARS-CoV-2 genetic material as unvaccinated animals.

This could be due to the extremely high dose of virus received by monkeys after receiving the vaccine, says Sarah Gilbert, an Oxford vaccinologist who co-led the study with Vincent Munster, virologist at NIAID laboratories in Hamilton, at Montana. These doses ensure that animals are infected with the virus and may not reproduce natural infections. The study did not measure whether the virus was still infectious, says Diamond, and it could represent viral particles inactivated by the monkey’s immune response or the viruses administered by the researchers, not an ongoing infection.

Yet the result is “a concern” that raises the possibility that vaccinated people can still spread the virus, says Douglas Reed, an aerobiologist at the University of Pittsburgh in Pennsylvania. “Ideally, you want a vaccine that protects against disease and transmission, so that we can somehow break the chain,” he says.

One way to determine if vaccines can prevent transmission would be to study them in animals that are naturally susceptible to the virus and seem to be able to spread it, such as ferrets and hamsters, says Reed. He and other researchers are also wondering whether vaccines should also be tested in animals who develop a more serious disease than macaques, whose symptoms are mild.

Safety signs

Although it is difficult to assess the potential for vaccines to work, the latest data is less ambiguous about safety, say the researchers. The Moderna vaccine caused few serious and lasting health problems to the volunteers. The Oxford and Sinovac monkeys did not develop a more severe infection after the injection – a key concern as an inactivated vaccine against SARS (severe acute respiratory syndrome) has shown signs of this in animals.

Stanley Perlman, a coronavirologist at the University of Iowa in Iowa City, says that the animal studies conducted so far can only say a lot to vaccine developers. “People are doing their best,” he says. None of the data he has seen should deter developers from continuing human trials on humans to determine if they’re working.

Moderna will soon start a phase II trial involving 600 participants and hopes to start a phase III efficacy trial in July to test whether the vaccine can prevent the disease in high-risk groups, such as health workers and those with underlying medical problems. Zaks said new animal studies, including monkeys, are underway and it is not yet clear which animal will predict best if and how their vaccine works.

The Oxford team has already enrolled more than 1,000 people in their UK trial. This gave some volunteers a placebo, which could allow researchers to determine if the vaccine works in humans in the coming months. The team’s study of the monkeys was reassuring because it found no safety concerns, said Gilbert.

“We really don’t need more data from animal testing to continue,” she said. “If we get human efficiency, we have human efficiency, and that’s what counts. “

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