Dr. Lidia Oostvogels is feeling the pressure. After nearly two decades working on vaccine development, seeing the topic of her work – the coronavirus – in the news every day comes first for her. “It is very exciting and very motivating, but there is a lot of pressure,” he said.
Dr. Oostvogels leads human testing of a coronavirus vaccine for the German biopharmaceutical company CureVac , where she leads its infectious disease program, as well as the development of vaccines and therapies.
In January, after returning from the Christmas break, CureVac’s infectious disease team began discussing the outbreak in Wuhan and whether it could work on a vaccine.
“We had to convince our management that this was a project worth starting work on,” Dr. Oostvogels said, adding that they knew this was not another case of MERS or SARS where people started. to develop vaccines and then the viruses disappeared.Of course, it would have been much better if it had happened this time as well, but it didn’t.
Once the SARS-CoV-2 genome sequence was published in early January, CureVac scientists began working on finding the best way to make a vaccine to take into clinical trials, which test new vaccines and medications in people.
They had to develop and manufacture the vaccine candidate, called CVnCoV, test it in animals, and get the green light from regulatory authorities and ethics committees to start injecting it into humans, which began in mid-June.
This is where Dr. Oostvogels’ clinical development team came in. Their job is to “launch and run clinical trials.” It means designing the human trials, interpreting the entire “content” of the trial, including what to test in the subjects, who to test and whom to exclude, and interpret the results, and make decisions based on them.
MRNA
The CureVac vaccine is based on messenger RNA, or mRNA technology, which is relatively new, only about 20 years old. There are currently six such vaccines for COVID-19 in human trials around the world.
The mRNA translates DNA, the genetic code of living structures, into protein, the building block of most such structures, explains Dr. Oostvogels. An mRNA vaccine against COVID-19 works by instructing the body’s cells to produce a coronavirus-specific protein (not the virus itself), which triggers an immune system response that the body can repeat if it encounters the virus. real. No vaccine using this technology has been shown to be safe and effective to be licensed for human use.
The trials follow what Dr. Oostvogels calls the “bible,” the study protocol produced by her team that describes everything about the trial, from its procedures to how the data will be analyzed. CureVac also produced the Investigator’s brochure that lists detailed information about the vaccine, including the manufacturing process, previous test results, and potential risks. This guides the investigators conducting the trials, but also allows ethics committees and regulatory authorities to evaluate the vaccine and decide whether to allow the study to proceed.
CureVac is conducting its phase 1 trial – testing side effects and finding the best dose to propose – in the German cities of Tübingen, where the company is based, Munich and Hannover, and in Ghent (Belgium) . Where they would normally work with participants aged 18 to 40, as the burden of the disease affects older people, their participants reach up to 60 years of age.
When CureVac first announced its trials, they were inundated with emails from people wanting to participate, says Dr. Oostvogels. “It was really amazing.”
This is not how they got participants. Researchers from four university hospitals with recognized vaccination centers are conducting the trials to evaluate the CureVac vaccine. They have their own databases of volunteers and are the only ones who can include subjects in the clinical trial. Subsequent trials may include private medical practices.
The people involved had to be very healthy and were screened for underlying conditions. Smokers or people with a certain history of smoking due to pulmonary complications of COVID-19 were excluded for this trial. Pregnant women were too. In total, more than 200 people received 2 doses of the vaccine candidate one month apart, with increasing dose levels, staggered over time.
Once vaccinated at one center, the recruited volunteers spent four hours under observation, returned the next day, and received a phone call the next. “It is only the beginning. This is intense, ”Dr. Oostvog said.
Participants are contacted 14 times, including at least 10 visits, and followed for about a year after the second injection.
Dose
One of the biggest questions is how high the dose should be. Dr. Oostvogels says that it is not possible to compare the dose with other types of vaccines , such as a subunit vaccine such as the flu vaccine, which uses part of a pathogen, or an attenuated vaccine such as chickenpox, which uses a virus. weakened as they work differently. It is also difficult to compare with other mRNA candidates, as none have been licensed.
The starting dose defined by Dr. Oostvogels’ team is a level based on CureVac’s previous work on a rabies vaccine, where two injections of mRNA at 1 or 2 micrograms safely induced neutralizing antibodies. “We knew from studying rabies that we could start relatively low because our platform, the way we make messenger RNA, is very powerful.”
Researchers start with low doses, 2 micrograms, and then increase them as they gather data and build a database. They will need to inject a number of subjects at different dose levels to compare for statistical purposes. And they will need to determine that the dose level elicits neutralizing antibodies in a sufficient number or percentage of subjects to move to the next phase of clinical development, says Dr. Oostvogels.
His opinion on the phase 1 trial is: “So far, so good”, although he will not reveal specific results. “I am excited and eager to move on,” she said. The first results will be published later this year.
In the near future, based on internal and external evaluation of the first results of phase 1, CureVac will begin phase 2a of trials to test safety and confirm the dose in Panama and Peru with about 700 participants. The age of the subjects will be raised beyond 60 years and the racial diversity will be increased using the study to determine if there are differences between the European and Latin American populations. “Regulatory authorities will be interested in seeing that it has been tested in a diverse population,” said Dr. Oostvogels.
Around November, CureVac aims to start the combined phase 2b / 3 study for safety and efficacy , with the first part involving the vaccination of several thousand people in Europe, as well as in several Latin American countries.
“We need to collect cases to evaluate the efficacy of the vaccine and for this it is necessary to be in countries where there are enough cases … And that is, for the moment, in certain Latin American countries,” he said. If all goes well, 30,000 subjects will be fully recruited.
Interruptions
Trials of an independent vaccine at the University of Oxford were recently resumed after it was stopped because a participant fell ill. Although the researchers call for greater transparency in the trials, and experts say the hiatus was also a sign of safety rigor, Dr. Oostvogels says outages happen all the time but are generally not news . “Now everyone is looking at us,” he said.
He believes that it is important to keep people abreast of trials, as he says there is a perception and criticism that research is moving too fast and safety is not taken into account.
“I think what is very important is that the public sees that if something like this happens, the study is stopped, the evaluation is done in a decent way,” he said.
CureVac CEO Franz-Werner Haas has said his vaccine could be available in mid-2021 at a cost of € 10-15 per dose. CureVac’s vaccine candidate currently requires to be frozen for storage and transportation, but the company is aiming for a final vaccine that can be stored at the standard 2 to 8 ° C temperature. Dr. Oostvogels says this is less cumbersome since freezers are not always available and are more expensive, and the vaccine would not require thawing before being injected.
He says the job is exciting but stressful given its volume and high expectations. There is little room for error or delay. “People are dying from this disease as we speak, so if you are slow or screw things up because you don’t work well enough it has … an immediate impact,” he said.
It also means that vacations are rare due to the risk of quarantine. “With the current workload, I can’t afford not to be able to go to the office.”
For her, the optimal result is a vaccine that can protect anyone who wants to be protected. He thinks of the vulnerable members of our societies, in particular, like his mother who is 80 years old and lives alone. “Fragile people who at the moment have no choice, because they do not have the vaccine, now have to stay at home, away from everyone, because the outside world is too dangerous for them.”
In July 2020, the European Investment Bank and the European Commission provided CureVac with € 75 million to fund large-scale development and production of vaccines, including CureVac’s candidate vaccine against SARS-CoV-2.
Artículo original
This article was originally published in Horizon, the EU Research and Innovation Magazine
