Time 24 News (EUA)

Combining different vaccines could increase protection against covid-19, say scientists

Publicado em 03 julho 2020

Por André Julião | Agência FAPESP

Even before the World Health Organization (WHO) announced covid-19 as a public health emergency of international importance, in March this year, the search for a vaccine had already begun in several parts of the world. Some of these studies have advanced with unprecedented speed in history and, just seven months after the emergence of Sars-CoV-2, 18 of the more than 140 formulations created from different concepts are already being tested in humans.

Two of the candidates who are in the most advanced stage of development – known as a phase 3 clinical trial, whose objective is to evaluate the vaccine’s effectiveness in a large group of volunteers – are beginning to be applied experimentally in Brazil. One of them, ChAdOx1 nCoV-19, was developed by the University of Oxford, in the United Kingdom, and licensed to the AstraZeneca laboratory. The other, named Coronavac, is the result of work done by the Chinese company Sinovac Biotech, which signed an agreement with the Butantã Institute.

As it is one of the places where the new coronavirus circulates the most today and where more cases of covid-19 are confirmed every day, Brazil has become the ideal place for studies of vaccine efficacy and, soon, other potential candidates should arrive by on here. But it is not a race to see which one is the best or which one will get regulatory approval first, say the researchers involved in clinical trials. The more vaccines that are shown to be able to protect at least some of those immunized, the more chance that humanity will have to turn covid-19 into a disease that can be controlled, such as the flu.

The evaluation was made by the participants of the online seminar “Vaccines against covid-19 being tested in Brazil”, held last Thursday, 2, by Canal Butantan in partnership with Agência FAPESP.

“Having several vaccines against covid-19 approved can be useful, as it is possible that the best strategy to induce a protective immune response is to combine several formulations. In addition, all these ongoing studies allow us to learn more about the immune response against Sars-CoV-2. Understanding how these vaccines protect can give us a clearer idea of ??what is the marker of protection against covid-19, which can accelerate future studies “, said the professor of the Faculty of Medicine of the University of São Paulo Paulo (FM-USP) Esper Kallás, who coordinates in Brazil the phase 3 trial with Coronavac. The research, which will include almost nine thousand Brazilian volunteers in different states, is sponsored by the Butantã Institute.

Made with a viral strain isolated from a patient in January, and then inactivated in the laboratory by means of chemical processes, Coronavac advanced quickly thanks to the knowledge generated when searching for a vaccine against Sars-CoV-1, the coronavirus that between 2002 and 2003 caused the epidemic of severe acute respiratory syndrome (SARS) in China and in some other countries, said Ricardo Palacios, medical director of Clinical Research at Instituto Butantã.

“The SARS vaccine advanced to phase 1 of clinical trials. Then the virus was contained and the project was stopped. But the knowledge of how to develop vaccines against a coronavirus was harnessed. The company followed a very traditional path in a very long time. Usually, the different stages of pre-clinical and clinical tests are done one after the other, but they did several at the same time, “said Palacios.

The safety of Coronavac and its ability to induce a defense response in the body have been tested on different species of animals. It was observed that immunization significantly reduced the viral load in the nasal mucosa of infected animals and provided significant protection against lung infection.

In phases 1 and 2 of the clinical tests, the safety and immunogenic potential of different doses of the vaccine were tested, with different intervals between the two doses administered. To date, it has been observed that 90% of the volunteers who received the two doses developed neutralizing antibodies against Sars-CoV-2.

The length of time these antibodies remain in the body and their protective potential against covid-19 – or at least against the development of severe symptoms of the disease – is something that only phase 3 clinical trials will be able to inform, the researchers commented during the webinar.

“The production of protective antibodies is the main mechanism of action of most vaccines. But in the case of some diseases, for the performance to be good, the vaccine also needs to be able to teach defense cells to act against the pathogen, as this is the case for new vaccines against herpes zoster, used in people over 50 years old, “explained Kallás.

According to the participants of the event, both Coronavac and ChAdOx1 nCoV-19 appear to be able to induce both the production of neutralizing antibodies and the so-called cellular immunity, which is the training of certain types of lymphocytes so that they become able to recognize and attack cells infected with Sars-CoV-2.

In the case of the British vaccine, the strategy adopted was to use a virus that causes influenza in apes as a vector to induce in the human body the production of one of the proteins of the new coronavirus, known as spike. Present on the surface of the microorganism, this spike protein connects to a receptor on the human cell membrane to infect it. In theory, if the body develops defenses against this protein, it could prevent the virus from entering cells and being able to replicate if the person is infected.

The strategy had been developed in Oxford for some years to create a vaccine against the Middle East respiratory syndrome (Mers), caused by the coronavirus Mers-CoV. This allowed the group to move quickly towards the clinical phase of ChAdOx1 nCoV-19, said Pedro Folegatti, a researcher at the Jenner Institut, the vaccine research center at the British university.

“The advantage of this technology is that the vector can be adapted to other diseases and it is considered a good inducer of humoral response. [anticorpos] and cellphone. Other groups are testing similar methodology for influenza, tuberculosis, Rift Valley fever, chikungunya and zika. All studies show a consistent profile of safety and immunogenicity with a single dose, “said Folegatti.

Pre-clinical tests indicated that the vaccine was effective in protecting the lower respiratory tract infection, which includes the trachea, lungs, bronchi, bronchioles and pulmonary alveoli. However, it did not show a significant reduction in the viral load in the nasal mucosa of the animals.

Phase 1 clinical trials with ChAdOx1 nCoV-19 started on April 23 with 330 volunteers and, about a month later, phases 2 and 3 started. This last phase will include around 50 thousand volunteers in several countries, 5,000 in Brazil.

“Negotiations to bring the phase 3 trial to Brazil started in May. The country had an upward curve of infection and the city of São Paulo, then, was the epicenter of infections in the country. Second was Rio” , said the professor at the Federal University of São Paulo (Unifesp) Lily Weckx, who coordinates the São Paulo research arm with the Oxford vaccine. According to her, there will also be vaccination of volunteers in Bahia.

The agreement signed between AstraZeneca and the Oswaldo Cruz Foundation (Fiocruz) provides for the transfer of the technology to Brazil and the license to produce the immunizer in the country if it is approved by regulatory agencies.

“Brazil has large groups involved in several vaccine studies against covid-19 and, in my opinion, this is something strategic for the country. Since unfortunately our epidemic situation made us the ideal place for phase 3 trials, which at the less does this facilitate the negotiation with the developer companies, so that, if one or more vaccines are approved, these immunizers are available to the Brazilian population, including the most disadvantaged “, said Kallás.

When will the vaccine be ready?

Ongoing clinical studies predict that immunized volunteers will be followed for 12 months. However, according to Palacios, it is possible that a preliminary result will be announced before the deadline.

“If the number of cases among those immunized remains at a level considered satisfactory, an independent group of scientists will be called in to make an assessment. If they conclude that the preliminary result of effectiveness was statistically significant, it could be announced to the public,” said the director of Butantan.

The percentage of people that the vaccine needs to protect to be considered effective, however, is still unclear. WHO recommends somewhere between 50% and 70%. Recent guidelines released by the Food and Drug Administration (FDA) state that, in order to be registered in the United States, the immunizer must protect at least one in two people vaccinated. In Palacios’ assessment, this level of effectiveness would be sufficient.

“Whatever the approved vaccine, we will not end the coronavirus. It is here to stay and will accompany us throughout our lives. The goal of vaccines is to protect against disease and not against infection. If we can achieve levels of at least minus 50%, we avoid the big problem of overload in the health system and the demand for intensive care. Thus, we converted covid-19 into something controllable “, he said.

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