(23–41%) death 77% (67–83%) 79% (77–80%) 78% (77–80%) 67% (64–71%) 35% (24–45%) the confidence interval includes zero, so it is possible that vaccination had no effect. specific populations on 21 october 2021, the who recommended a third dose as part of the initial course for older adults 3–6 months after the second dose and for immunocompromised individuals 1–3 months after the second dose because these groups mount a weaker immune response compared to healthy adults. where supplies are limited, the third dose for seniors should be given after achieving high coverage with two doses. manufacturing brazilian version of coronavac, filled and finished by instituto butantan as an inactivated vaccine like the sinopharm bibp vaccine and covaxin, coronavac uses a more traditional technology that is similar to the inactivated polio vaccine. initially, a sample of sars-cov-2 from china was used to grow large quantities of the virus using vero cells. from then on, the viruses are soaked in beta-propiolactone, which deactivates them by binding to their genes, while leaving other viral particles intact. the resulting inactivated viruses are then mixed with the adjuvant aluminium hydroxide. coronavac does not need to be frozen, and both the vaccine and raw material for formulating the new doses could be transported and refrigerated at 2–8 °c (36–46 °f), temperatures at which flu vaccines are kept. coronavac could remain stable for up to three years in storage, which might offer some advantage in vaccine distribution to regions where cold chains are not developed. in november 2020, brazil's instituto butantan began building a facility to manufacture 100 million doses of coronavac a year, with a target completion date in september 2021. on 10 december, são paulo governor joão doria said that in the interim, prior to the local manufacture of coronavac, instituto butantan aimed to fill and finish 1 million doses of the vaccine per day. in april 2021, sinovac said its third manufacturing plant for coronavac was ready and had started manufacturing bulk vaccine ingredients, doubling its annual capacity to 2 billion doses. in april 2021, bio farma of indonesia had filled and finished 35 million doses of coronavac, but was facing some production delays because of diminished supply of bulk delivered coronavac from china. in may 2021, malaysian company pharmaniaga obtained local approval for its fill and finish coronavac. in may 2021, turkey was provided a license to produce coronavac. in may 2021, hungary announced an agreement to fill and finish coronavac, with the goal to eventually manufacture it locally in a new plant in debrecen. in june 2021, egypt announced that it will produce about 40 million doses by the end of the year. distribution of the locally produced vaccine will begin by august and it will be used locally and sent to other african nations. history clinical trials for broader coverage of this topic, see covid-19 vaccine. phase i–ii in april 2020, coronavac began phase i–ii trials in china with 744 participants on adults over the age 18–59, and in may, coronavac began phase i–ii trials in china with 422 participants on elderly adults over the age 60 and above. preliminary results indicate that neutralizing antibodies fell below the seropositive threshold 6 to 8 months after the first two doses, and that a third dose given 6 or more months after the second dose raised neutralizing antibody levels beyond that of an initial course consisting of 3 doses. in the phase ii trial completed in july 2020 published in the lancet, coronavac showed seroconversion of neutralising antibodies for 109 (92%) of 118 participants in the 3 μg group, 117 (98%) of 119 in the 6 μg group, after the days 0 and 14 schedule; whereas at day 28 after the days 0 and 28 schedule, seroconversion was seen in 114 (97%) of 117 in the 3 μg group, 118 (100%) of 118 in the 6 μg group. phase ii results for older adults published in the lancet showed coronavac was safe and well tolerated in older adults, with neutralising antibody induced by a 3 μg dose similar to those of a 6 μg dose. phase iii in july 2020, sinovac began phase iii trials to evaluate efficacy and safety on 9,000 volunteer healthcare professionals in brazil, collaborating with butantan institute. on 19 october, são paulo governor joão doria said the first results of the clinical study conducted in brazil proved that among the vaccines being tested in the country, coronavac is the safest, the one with the best and most promising immunization rates. on 23 october, são paulo increased the number of volunteers in the trial to 13,000. brazil briefly paused the trials on 10 november after the suicide of a volunteer before resuming them the next day. the suicide was unrelated to the vaccine trial. in august, a trial was started in chile run by pontifical catholic university of chile which was expected to include 3,000 volunteers between the ages of 18 and 65. in august, sinovac began trials in indonesia with bio farma in bandung involving 1,620 volunteers. in september, turkey began trials with 13,000 volunteers on a two-dose 14-day interval. the monitoring process took place at 25 centers in 12 cities across the country.the governor of west java ridwan kamil participating in phase 3 trial of the sinovac covid-19 vaccine in indonesia. in october, sinovac began trials in china involving 1,040 volunteers. in april 2021, sinovac began phase ii/iii trials for the elderly aged 60–80 in the philippines involving 352 volunteers. children and adolescents trials in september 2020, sinovac began phase i–ii trials in china on children and adolescents ages 3–17. in may 2021, sinovac began phase iib trials in china with 500 participants for children and adolescents 3–17 years old. in june 2021, it was announced that the vaccine was safe and immunogenic in this age group. in july, sinovac began phase iii trials in chile with 14,000 participants for children and adolescents and expand from 6 months to 17 years old. results of phase iii trials peer-reviewed phase iii results from turkey showed an efficacy of 83.5% (95% ci, 65.4–92.1%). the final efficacy rate was based on 41 infections, 32 of which had received a placebo. the vaccine prevented hospitalization and severe illness in 100% of cases, with all six people who were hospitalized in the placebo group. the final results were based on 10,218 participants in the trials. phase iii results from brazil submitted to lancet showed 50.7% efficacy at preventing symptomatic infections, 83.7% effective in preventing mild cases needing treatment. efficacy against symptomatic infections increased to 62.3% with an interval of 21 days or more between the doses. a total of 12,396 volunteers participated in the study between 21 july and 16 december 2020. all participants received at least one dose of the vaccine or placebo. of this total, 9,823 participants received both doses. further detail published by sinovac showed an efficacy 50.65% (95% ci, 35.66–62.15%) against all symptomatic cases, 83.70% (57.99–93.67%) against cases that require medical treatment, and 100.00% (56.37–100.00%) against severe, hospitalized and fatal cases. in the placebo group (n=4870), there were 168 covid cases, 30 cases requiring medical attention, and 10 severe cases including one death. in the vaccine group (n=4953), there were 85 covid cases, 5 cases requiring medical attention, and no severe cases or deaths. on 1 april 2021, a preliminary report from a phase iii clinical trial in chile revealed that coronavac is safe and induces humoral and cell-mediated immunity in adults (18–59 years old) and the elderly (60 years or older) similar to previous phase ii trials conducted in china with the same age groups and immunization schedule consisting of two doses with a 14-day interval. the side effects were mild and local, mainly limited to pain at the injection site, which was more common in adults. seroconversion rates for adults 14–28 days after the second dose were 95.6% for the igg specific against the s1-rbd (receptor binding domain of the s1 subunit of the spike protein) and 96% for neutralizing anti-s1-rbd igg. for the elderly, seroconversion rates were 100% 14 days and 87.5% 28 days after the second dose for the s1-rbd specific igg, 90% 14 days, and 100% 28 days after the second dose for neutralizing anti-s1-rbd igg. as found in studies in animals, seroconversion rates for igg specific against the n (nucleocapsid) protein were weak for both groups, although coronavac contains significant amounts of the n protein. a robust increase of t helper cells (cd4+) secreting interferon gamma was detected 14 days after both doses in response to stimulation with peptides of the s protein and of other viral particles, but the response to s protein peptides was reduced in the elderly due to a natural reduction of activated cd4+ t cells in this age group, as found in studies of other vaccines. the immune response of cytotoxic t cell (cd8+) was not as robust. the observed cd4+ t cell response is considered a balanced immune response capable of viral clearance and is similar to that observed in other covid-19 vaccines, such as bnt162b1 and convidecia. variability in results in early january 2021, brazilian health officials announced that the vaccine had an efficacy of 78%. one week later, they revised this figure to 50.4%, stating that the revised figure now included "very mild" cases of covid-19 among trial participants which were omitted in the earlier analysis. ricardo palácios, medical director of brazil's instituto butantan, said sinovac's relatively low efficacy rate of 50% was due to more rigorous standards for what counted as an infection among trial participants. the institute split cases in six categories: asymptomatic, very mild, mild, two levels of moderate, and severe; the first two didn't require medical assistance. possible explanations for lower efficacy rate included: trial was largely made up of frontline health care workers who were more exposed to the virus; two vaccine doses were given at shorter intervals (2 weeks); counting very mild cases; and the gamma variant (lineage p.1), more transmissible and perhaps evaded immunity better, was circulating. according to instituto butantan director dimas covas, the brazilian group was considered more vulnerable to infection and exposure to higher viral loads. in turkish and indonesian phase iii trials, the composition of volunteers was similar to that of the general population. variants on 10 march, instituto butantan director dimas covas said coronavac was efficacious against three variants of covid-19 in the country; alpha (lineage b.1.1.7), beta (lineage b.1.351), and lineage b.1.1.28 (identified in brazil), from which gamma and zeta (lineages p.1 and p.2) descend. preliminary results from a large study of health care workers suggest one dose of coronavac is still about 50% effective against symptomatic covid-19 in manaus. in april 2021, it was reported that over 75% of new cases were being caused by the highly transmissible gamma variant. in june, thailand's public health ministry stated the vaccine had 71%-91% efficacy against infection by the alpha strain. in june 2021, reuters reported that more than 350 indonesian doctors and medical workers out of 5,000 in kudus contracted the delta strain despite being vaccinated with the coronavac, an infection rate of 7%. in response, griffith university epidemiologist dicky budiman questioned the efficacy of coronavac against the variant but overall still recommended that people take the vaccine, expressing "confidence that to a certain degree sinovac has effectiveness against the new variant". he stated that the situation was due to various factors, including a "lack of proper protective gear and the overall situation in indonesia". the vast majority of those infected were protected from severe symptoms and recovered without hospitalization. a hong kong 2022 study of the ba.2 omicron variant comparing coronavac with bnt162b2 (pfizer) found effectiveness of 32.4% and 41.4% (respectively) in preventing infections with two doses, and 41.6% versus 50.9% (respectively) in preventing infections with three doses. another hong kong study of the ba.2 omicron variant comparing coronavac with bnt162b2 for adults over age 60 found effectiveness of 69.9% versus 89.3% (respectively) in preventing severe disease or death with two doses, and 97.9% for both vaccines with three doses. authorizations full authorization emergency authorization allowed for travel eligible covax recipient