During the first day of the Symposium regarding the CoronaVac, different researchers discussed from the basic aspects of nature of the SARS-CoV-2 virus , to the production of the vaccine of CoronaVac, the results to its efficacy, efficiency and safety. Primarily Dr. Yalling Hu, representing Sinovac, related that the production and distribution of the vaccine depends on the scientific results, quality of collection and cultivation of the virus, efficiency in production and a good supply chain.
The Covid-19 sickness probably emerged in november of 2019, with the first alert being in China on November 8th of 2019, and on December 31st of 2019 the OMS released the first worldwide alert. On January 7th, the new coronavirus was identified and named as SARS-CoV-2, and in March of 2020 the OMS declared the pandemic state. In April of 2020 the virus was worldwide spread.
Sinovac approved internally the beginning of a vaccine project against SARS-CoV-2 on January 28th of 2020. In March, the first animal testing and the construction of the industrial plant has initiated. The preclinical trials on monkeys provided data for establishing the best dose and immunization scheme. By the half of April the clinical trials of research for Phase 1 and 2 were initiated. The industrial plant was concluded on June 30th of 2020 and no longer afterwards they began the studies of Phase 3. On February 2nd of 2021 the commercialization of the vaccine was allowed and in April of 2021 the productive capacity was evaluated in 2 billion annual doses.
Doctor Hu presented the motives of choosing the vaccine with inactivated virus. The platform for this technology was well established and the vaccine possess a great amount of antigens, hoping that it induces a good humoral immune response (antibodies) and/or cellular, used against the diverse of viral proteins (Spike, nucleocapsid, membrane, viral envelope, non structural proteins and varied ORFs) and not just against Spike, which is the most exposed protein of SARS-CoV-2 that interacts with the receptor ACE-2, penetrating the host cells. It is important to emphasize that all the viral proteins are essential for all the phases of infection, and, therefore, antibodies or immune cells against them can generate protection. Besides, this kind of vaccine manifests historically a good profile of safety for application in children and teenagers. Since Sinovac has an accumulated experience of 20 years with inactivated vaccines, it was possible to produce the same kind on a large scale (billions of doses), in record time.
At present, after the vaccination of millions of people around the world, Sinovac is evaluating the efficacy of its vaccine during the application of booster doses, and its use against new variants.
CoronaVac was tested and used in multiple countries of different continents, but we highlight the studies realized in China, where the vaccine was developed, Chile, Turkey and Brazil. In all those countries, different scientists evaluated the vaccine, initially with a restricted and controlled number of individuals and measured the efficacy of the vaccine and the adverse effects presented (low, moderated and high). Regarding all the vaccines that were liberated by the regulatory agencies of health, the clinical trial elapsed in normality, not presenting any serious case of adverse reaction.
The efficacy of a vaccine can be measured in different ways, through the measure of antibodies against the viral structure, presented on the blood of the individuals that took part in the study, through the clinical trials of the inactivation of the virus with the antibodies obtained in each individual (neutralization), measuring the levels of activation of B or T cells (CD4+ or CD8+), or measuring the memory cells B or T.
Doctor Serhat Ünal presented the results of Turkey, including more than 10 thousand individuals, distributed in different regions of the country, immunized with two doses of CoronaVac. This clinical trial Phase 3 began in September of 2020 and ended in February of 2021. The efficacy for asymptomatic patients was 83,5% and, 100% for hospitalization cases. During this study it was clear that the vaccine induced a high tax of seroconversion, which means the production of antibodies against the virus, especially the production of neutralizing antibodies. About the cell immunity, Doctor Ünal called attention to the fact that the vaccination induced the activation of memory T cells comparable with the one obtained by convalescent individuals. These cells can respond quickly to a new viral challenge, generating a long term protection.
The second study was presented by Doctor Rafael Araos regarding the efficiency of CoronaVac in Chile. During this populational study involving more than 10 million people with age above 16, could be observed a decrease in incidence of serious cases in all age groups, after a vaccination with two doses of CoronaVac. The efficiency was calculated in about 90% of reduction of hospitalization and 86% of reduction for ICU internalizations. Related to the booster dose, the third dose, there were presented heterologous schemes, with Pfizer and AstraZeneca vaccines, and homologous with CoronaVac vaccines. The efficiency of the hospitalization cases was about 95% on heterologous scheme and 87% for homologous.
The third study, presented by Doctor Marcos Borges from USP of Ribeirão Preto, was Project Serrana, an unprecedented and controlled study of vaccination with CoronaVac initiated in February of 2021, on a population of São Paulo countryside. All the adult habitants of the city (83%) were asked to participate in a study, with 62% taking a part in it and 61% concluding the vaccinal scheme. As a result, the efficiency against hospitalization and deaths was 95%. The population was divided in 4 groups which each one had a different vaccinal beginning, methodology and scaling. The results demonstrate that the vaccinal effect of the last group (the last one to be vaccinated), had an anticipated protective response, probably generated by the protector effect of the other 3 groups, which were vaccinated before. Borges highlighted, by the end of his presentation, that probably the booster dose of the vaccine induced an increase in the antibodies titles (Anti-S and Anti-N) for the eldery population. This study showed itself interesting by representing an analisis model of vaccinal response of a population.
The last and fourth study, presented by Doctor Kallás, is a clinical trial of CoronaVac in Brazil with 13 thousand volunteers with more than 18 years of age and two doses of the vaccine. As a final result, the efficacy was 83,7% to reduce the cases of hospitalization and 100% in protection against deaths. Kallás et al. measured the humoral response in a long term, during a year, in adults, eldery, placebo group, convalescents and hospitalized patients. Adult individuals showed higher titles (Anti-N and Anti-S) compared to elders, and those titles maintained constants during 360 days. The elders had a decrease of antibodies after, about, 90 days. They calculated the correlations between titles of total antibodies and neutralizing antibodies against the Spike protein and RBD (region that connects to the receptor ACE-2), which presented results near 60% (n=0.6) with significant statistics. Afterwards, Doctor Kallás presented the cell response of lymphocytes CD4+ of memory, which rose in 180 days after the vaccination, as for adult individuals as for elders. This result is important by being related to a probable long term protection induced by the vaccine.
In summary, the studies realized in Turkey, Chile and Brazil, had as a goal to measure the efficiency of CoronaVac in those countries. The results were widely satisfactory, being the calculated efficiency, during the analisis term, was higher than 90% for the production of antibodies against the virus, and about 90% in reduction of the necessity of hospitalization, UCI hospitalization and deaths. The efficiency is measured through a temporal cut in a certain population. It is important to highlight that the SARS-CoV-2 had a high tax of mutation, likely the most RNA viruses. So, due to the high mutational tax and the evolutionary selection, variants may appear and become extinct with impressive dynamics. To summarize, every 2 or 3 months variants may present in each local scenario, and new studies must be realized to know if each vaccine will be able to induce an immune response to these variants, and how these mutations modify the virus structure, its pathogenicity and its propagation capacity. Due to this day, it was observed a good protector behavior of all the vaccines against most of the variants.