Vaccines to fight COVID-19

Vaccines to fight COVID-19. Covid-19 vaccines are being developed at an unprecedented speed and, in addition to the speed, ongoing projects seek to demonstrate the efficacy and safety of new technologies, which could in the future modernize other vaccines already in use around the world. According to the World Health Organization (WHO), of the nearly 200 proposed vaccines in testing, 44 have reached the human trial stage, called clinical trials. Of these, a group of 10 projects have reached phase three of the studies, in which tens of thousands of volunteers are recruited to see if the vaccine can really protect without harming health. Because it still has extensive circulation of the virus, which speeds up research, Brazil has hosted some of these tests with thousands of participants. Vaccines developed by AstraZeneca / Oxford, Sinovac, Janssen and Pfizer / Biontech / Fosun Pharma have received clearance for large-scale trials in the country.

With techniques already used by science or new ways to induce the immune response, the vaccines that have reached the last phase of experimentation have the same goal: to bring the body important information that will trigger the production of defenses to the new coronavirus in advance. Agência Brasil explains the main strategies developed by scientists to make vaccines effective and safe.

The government of Sao Paulo tests with the vaccine against the new coronavirus. – Press release / Government of Sao Paulo

Protein S

When the body makes antibodies against a virus, it is stimulated by specific structures that make up these beings. In the case of the coronavirus that causes covid-19, scientists have discovered that protein S, which forms the crown of thorns that gives the virus its name, is the structure that most induces the immune system to produce antibodies. This protein is also crucial for infection: it is with the small spines formed by the S protein that the new coronavirus connects to human cells and initiates the invasion to replicate.

• 

The director of the Brazilian Society of Immunizations (SBIm), Renato Kfouri, explains that anticipating body contact with protein S is a common strategy for major ongoing projects. “Vaccines are primarily aimed at inducing antibodies against this S protein. Antibodies are, in general, neutralizing. They are able to neutralize the activity of the virus “.

Inactivated viral vaccines

Among the ten vaccines that have reached phase 3 clinical trials, three proposals developed in China use the technique known as an inactivated virus vaccine: that of Sinovac, which is being tested in Brazil in collaboration with the Butantan Institute and the government of Sao Paulo, that of Sinopharm with the Wuhan Institute of Biological Products, and another of Sinopharm with the Beijing Institute of Biological Products.

Boxes with potential vaccine from Sinovac against Covid-19 in Beijing – Reuters / All rights reserved

The strategy gets its name because the vaccine contains the dead virus itself, which is technically called inactivated. These vaccines are common in the prevention of various diseases, such as polio, hepatitis A and tetanus, and cause the body to produce defenses against early and harmless contact with the virus.

“In this technology the virus is grown in the laboratory and, after taking a large amount, it inactivates, kills the virus in the most common language, through temperature or chemicals. It is a whole virus, dead, inactivated, but with these proteins preserved and capable of inducing an immune response ”, explains Kfouri. “The only difficulty is that you need laboratories with a high level of biosecurity to manipulate the live virus, you have to cultivate it and you have the time to multiply these viruses and then inactivate them. These are processes that require longer times and a maximum level of safety for the laboratories, because they will treat viruses with infectious potential ”.

Vector viral vaccines

To make the body produce antibodies capable of neutralizing protein S, non-replicating viral vector vaccines bring an innovative proposal: the new coronavirus protein is inserted into another virus, modified in the laboratory, to transport it to the human and non-human body. multiply. Once the protein reaches the body, the immune system identifies it and produces structures that can prevent it from acting in the future, when the new coronavirus attempts to cause infection.

This technology was already being studied to produce vaccines against the Ebola virus and coronavirus that caused outbreaks in previous years, such as SARS-CoV-1, which explains how quickly research could be directed to SARS-CoV-2. Projects like that of the American Janssen and that of the Chinese CanSino use human adenoviruses to transport protein S in the human body.

The same is proposed by the Gamaleya Research Institute of Epidemiology and Microbiology of Russia, with the difference of using two different types of adenovirus, one in each vaccine dose. If proven and registered by the National Health Surveillance Agency (Anvisa), the Russian vaccine must be manufactured in Brazil by the União Química Group.

The British proposal from pharmaceutical company AstraZeneca and the University of Oxford uses a chimpanzee adenovirus as a viral vector. This vaccine is being tested in Brazil and the federal government has signed a technology transfer agreement so that the Oswaldo Cruz Foundation can produce it. Vaccine in AstraZeneca tests – REUTERS / Dado Ruvic / Illustration / Copyright

“Vaccines come from live adenoviruses, but they don’t replicate. They remove the proteins responsible for their multiplication from the adenovirus structure. These adenoviruses are cold viruses, ”explains Kfouri, who adds that adenoviruses were chosen to carry protein S because they elicit little immune response, allowing the body to focus its reaction on the coronavirus protein.

Genetic vaccines

Another technology in testing, never used before in immunization, is that of RNA or DNA vaccines, which insert the nucleic acids of the new coronavirus into the human body. So far, only vaccines that use RNA have reached phase three of clinical trials and their functioning predicts that upon entering the body, the nucleic acid of the novel coronavirus will cause human cells to produce protein S, which, a instead, it will activate the production of defenses in the body.

If efficacy and safety are confirmed, this technology is considered to be faster for large-scale production, as the vaccine uses synthetic RNA, which exempts from growing the virus in the laboratory. Phase 3 studies seeking to confirm the efficacy and safety of RNA vaccines are under the command of the American pharmaceutical company Moderna in collaboration with the US National Institute of Allergy and Infectious Diseases, and the research group that it also brings together the American company Pfizer, the German Biontech and the Chinese Fosun Pharma.

Kfouri explains that research using RNA vaccines has also moved quickly because it started with studies already underway to develop vaccines against other coronaviruses and Ebola. “This technology has the potential to be used in many other vaccines due to its rapid manufacturing capability. It may be that, if it works, we will migrate other vaccines that we already use for this platform today ”.

Subunit protein vaccines

Vaccine – REUTERS / Dado Ruvic / Illustration

The fourth technology that is under development and has already reached phase 3 studies is that of subunit protein vaccines, which propose the injection of the protein S and other proteins of the new coronavirus directly into the human body, without the use of viral vectors.

Of the ten vaccines in phase three studies, the only one of its kind is the one produced by the American pharmaceutical company Novavax.

“They carry parts of the virus, like we do with the flu and the HPV vaccine. We take pieces of protein S, protein M, protein E and we make vaccines with these fragments of the virus, which also needs to be cultured and inactivated, but instead of the whole virus, the vaccine takes viral particles, subunits of the virus. “