In the US, another candidate vaccine, developed by the biotech company Moderna, has started its Phase III study this week. For this study, 30,000 volunteers at 89 locations in the US will receive a new mRNA vaccine that would be the first of its kind if approved by the National Institutes of Health.
Participation in a vaccine study is a painstaking and time-consuming process. Volunteers should be carefully screened and monitored for months, with a small risk of potentially harmful side effects. But according to Barbosa, the candidate vaccine is worth all of this. “It is my civic duty to do this. It’s for charity. Without the vaccine, we will never know when this epidemic is over. ” (This is how we know when there is a vaccine against COVID-19.)
Barbosa has been head of the ophthalmology department of the Rede D’Or São Luiz, a system of hospitals across Brazil, since 2007. Between the end of March and June, the number of visits to these clinics fell from a hundred to several dozen a day. Most patients come for the treatment of serious eye diseases such as glaucoma and diabetic retinopathy.
During the worsening COVID-19 crisis in Brazil, Barbosa wanted to do something about the virus, so she asked the board of directors of the Rede D’Or São Luiz for permission to work with other health workers on the frontline. Her request was rejected: she was told that she had not worked in primary care for long enough. “I was very frustrated that I was not allowed to treat COVID-19 patients,” says Barbosa.
So when Brazilian regulator Agência Nacional de Vigilância Sanitária approved the clinical trial for ChAdOx1, she took the opportunity to volunteer to join. “Now I’m somehow involved,” she says.
A new candidate
Oxford University was already working with so-called “viral vector” technology on a vaccine for another type of coronavirus, the MERS virus, when the current pandemic broke out. Since the MERS virus emerged in Saudi Arabia in September 2012, a total of 2,494 cases have been reported in 27 different countries, of which 858 are fatal.
The Oxford study was well advanced when the new coronavirus SARS-CoV-2 first appeared in December 2019. So the scientists used their experience with MERS technology as a starting point for the search for a vaccine. They injected protein (from the protrusions that surround the SARS-CoV-2 virus and help it penetrate other cells) into a common adenovirus that causes colds. The adenovirus thus obtained, which was genetically attenuated and could not multiply in human cells, served as a “viral vector”.
A viral vector works “like a Trojan Horse,” says Sue Ann Costa Clemens, physician and coordinator of the Brazilian study. “The adenovirus carries particles of the SARS-CoV-2 virus, the protein of the protrusions. The protein triggers an immune response when injected into humans. ”
The preliminary results from the first two phases of the study were published in the medical journal on July 20 The Lancet published. Some participants had some mild side effects such as headache and fatigue, but none of the volunteers experienced serious reactions.The researchers also found that the Oxford vaccine elicited a strong immune response from the two main immune systems that the body uses to recognize pathogens and eliminate: antibodies and T cells.
Clemens was responsible for selecting Brazil as the country where the Phase III study for the ChAdOx1 vaccine would be conducted. The 52-year-old doctor from Rio de Janeiro has lived in Italy for twenty years, where she is a professor of childhood infectious diseases at the Università degli Studi di Siena and has initiated the first international training in vaccology. In addition, she is coordinator of the Institute for Global Health and director of the university’s master’s program in Vaccology and head of the Scientific Committee of the Bill and Melinda Gates Foundation.
On May 5, Andrew Pollard, coordinator of the Oxford group developing the new coronavirus vaccine, invited Clemens to participate in the clinical studies of ChAdOx1; Pollard teaches vaccinology at the institute in Siena. Clemens immediately accepted the offer. Throughout her career, she has led similar studies involving large numbers of volunteers to be clinically tested. In 2005, she worked in Latin America on a study of a rotavirus vaccine that required 60,000 volunteers to be prepared for six months.
This time, Clemens first focused on the choice of test locations where the clinical tests would be conducted. She looked for places with well-trained medical personnel in an environment where large numbers of people were exposed to the SARS-CoV-2 virus. The Universidade Federal de São Paulo, where she received her doctorate and where she currently works as a researcher, fulfilled these conditions, and the institute agreed to cooperate.
“With a Phase III study, you want to prove that the vaccine protects people against the disease,” says Clemens. “How can we work as quickly as possible and make the vaccine available to the population in a short time?”
The study in Brazil started on June 28 in three centers, coordinated by Clemens. In total, five thousand volunteers, divided into two groups, are vaccinated. One group is vaccinated with the candidate vaccine ChAdOx1, the other with a control vaccine. This is a so-called ‘randomized double-blind study’, which means that the volunteers are randomly assigned to one of the two groups and that during the study neither the vaccinated person nor the researcher knows which vaccine has been administered to which test subject.
The researchers selected a quadrivalent vaccine against ACWY meningococci as a control agent. The dose is the same as that of the ChAdOx1 vaccine, so that the volunteers are given equal amounts of the ingredients of either vaccine. The researchers were already familiar with the side effects of the new vaccine, including pain and redness at the injection site and mild flu-like symptoms. The team chose not to administer a placebo vaccine – a ‘vaccine’ without any active substance – so that the volunteers would still have some benefit from the study. (The meningococcal vaccine is not widely administered in Brazil, according to Clemens, because it is quite expensive.)
Human guinea pig
Ophthalmologist Andréa Barbosa met the requirements for participation in the vaccine study: as a healthcare professional, she is at high risk of exposure to the coronavirus in her work, and she is between 18 and 55 years old.
Her first visit to the IDOR clinic in Botafogo took place on July 4. A team of nurses checked her parameters, height and weight. She was then asked a number of questions to ensure that she met all the criteria for the study. People with treatable complaints such as asthma are accepted, but patients with a chronic illness or disorders that weaken the immune system are refused.
“My case was a bit more complicated, because I sometimes have contact allergy, but they looked at that and found this type of allergy not a reason for exclusion,” she says. By contact allergy, she means a mild allergic reaction that she shows when her skin comes into contact with certain substances.