RIO DE JANEIRO, BRAZIL – The vaccine against Covid-19 from the Chinese manufacturer Sinovac is safe and is able to produce an immune response in the body 28 days after its administration in 97 percent of cases, according to a peer-reviewed article published on Tuesday, November 17th in the Lancet Infectious Diseases scientific journal.
The results are the based on the analysis of phase 1 and 2 clinical trials conducted in China in April and May with 744 healthy volunteers aged 18 to 59 and with no history of Sars-CoV-2 coronavirus infection.
Although the Coronavac vaccine is already in phase 3 trials (the last before approval) in humans in several countries, including Brazil, where the immunizer is being tested in partnership with the Butantan Institute, it is the first official publication of the trials of the preceding phases. All other Phase 3 vaccines had already had their Phase 1 and 2 results published.
Last week, Pfizer and Moderna released more advanced preliminary and encouraging phase 3 results based on interim data analysis. Both showed efficacy over 90 percent, but the details have not yet been published in a scientific journal.
The randomized, double-blind and controlled study (considered the gold standard because it splits the participants randomly into groups, with no knowledge of whether they are taking the vaccine or a placebo, to avoid bias) produced positive results, with the production of antibodies being confirmed after 14 days, with peak production at 28 days.
A total of 144 people were assessed in phase 1 and another 600 people in phase 2, totaling 744 volunteers, of which 743 were either administered the vaccine or a placebo (one volunteer gave up during the study).
A good news is that the vaccine induced the production of neutralizing antibodies, whose function is precisely to prevent the ingress of virus into the cells, suggesting that the vaccine can be effective in preventing infection and not only the development of the disease. However, the T lymphocytes, responsible for ensuring cell protection, have not been analyzed.
In phase 1, the subjects were randomly divided into two groups. The first group was administered the lowest dose of the vaccine and after seven days, volunteers in the second group were administered the highest dose. In each group a booster dose was administered 14 days later.
In phase 2, the 600 subjects were randomly divided into three groups. The first and the second were given the lowest and highest doses of the immunizer, respectively, and the third a placebo.
Seroconversion, i.e. the presence of specific antibodies in the blood against the coronavirus, was identified as early as 14 days after the first dose in phase 1, but only in half (12 out of 24) of the subjects who were administered the high-dose vaccine and in 45.8 percent (11 out of 24) of the subjects immunized with the lowest dose. After 28 days, this rate rose to 83 percent (20 out of 24). The presence of neutralizing antibodies was not detected in the subjects who were administered a placebo.
In the 600 phase 2 subjects, seroconversion was identified in 92.4 percent (109 out of 118) of those who were immunized with the lowest dose 14 days later and in 98.3 percent (117 out of 119) of those who were immunized with the highest dose 14 days later. After 14 days, when the second dose was administered, seroconversion was identified in 94.1 percent (111 out of 118) of subjects with the lowest dose and 99.2 percent (117 out of 118) of those who were given the most potent injection.
As both vaccines induced an immune response, the researchers state that there is no significant difference in dosage for the production of neutralizing antibodies, but rather in the time of administration. The two-dose scheme with a 28-day interval between them was the best to achieve a higher rate of antibodies in the blood more rapidly.
However, the authors state that, given the pandemic emergency situation, at a 14-day interval between doses it is now possible to detect antibodies in the blood, and this may be an option to immunize the population faster.
The adverse effects reported were mild, and the most common was pain on the injection site (reported by about 35 percent). There were no serious side effects that could signal a potential vaccine safety flaw.
Regarding the different dosages, both were well tolerated, with few significant differences. The authors state that, unlike other vaccines whose vaccine platforms are non-replicant viral vectors (such as adenovirus, technology used in the Oxford/AstraZeneca, Johnson & Johnson, and Sputnik V vaccines) and genetic (such as those of Pfizer and Moderna), fever was not a common Coronavac adverse effect.
The Sinovac pharmaceutical company vaccine is produced from inactivated viruses. The goal is to modify the Coronavirus Sars-CoV-2 making it non-infectious.
Until phase 1, scientists used the culture of Vero cells -alignment of cells commonly used in microbiological cultures, synthesized from cells isolated from the kidneys of a monkey species in the 1960’s and used until today- to multiply the Sars-CoV-2 in laboratory.
However, from phase 2 onwards, the company began to use bioreactors, a kind of industrial “cell factory” that uses heat, raw material (cells or parts of it) and movement to produce infected cells in large scale. The virus is then inactivated and incorporated into the vaccine.
The production of the vaccine with the total inactivated virus is similar to the one used for the production of the rabies vaccine. However, this type of vaccine requires extensive safety testing. Phase 3 which is in progress in Brazil should continue for at least six months.
In this third phase, some important doubts must be answered, such as the length of time the protection against the virus lasts; whether the immunizer is able to prevent the infection or simply protect against the most severe picture of the disease; and if the vaccine induces immune response of the T cells .
The company has also initiated a clinical study of people over 60 years of age, and the preliminary results of this study, released in early September, point to an immune response within this group, although lower than that observed in individuals aged between 18 and 59. The vaccine also proved to be safe in this age group.
There is still no vaccine approved for use in the population that fights Covid-19. Dozens of immunizers are being tested in humans, in different countries and with the use of different technologies.
Source: Folha de S.Paulo