CoronaVac

Manufacturing

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 would produce about 40 million doses by the end of that year. Distribution of the locally produced vaccine would begin by August and it would be used locally and sent to other African nations.

History

Clinical trials

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.

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% () against cases that require medical treatment, and 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

The World Health Organization (WHO) validated the Sinovac-CoronaVac COVID-19 vaccine for emergency use on 1 June 2021. The recommendation was given with limited evidence at the time of approval for groups other than healthy adults. The WHO Strategic Advisory Group of Experts expressed high level of confidence in the efficacy of the vaccine for adults, moderate confidence in the efficacy for older adults and individuals with comorbidities, moderate confidence in its safety for adults and low confidence in its safety for the elderly and individuals with comorbidities.

In late August 2020, China approved CoronaVac for emergency use to vaccinate high-risk groups such as medical staff. In early February, China approved CoronaVac for general use. On 5 June 2021, China approved CoronaVac for emergency use with children and adolescents for 3–17 years old.

In January 2021, Bolivia authorized use of CoronaVac.

In April, Panama approved emergency use of Coronavac.

On 4 May, the EMA's human medicines committee (CHMP) started a rolling review of CoronaVac.

In June, Bangladesh approved Coronavac for emergency use.

Society and culture

Economics

As of 7 July 2021, CoronaVac is the most widely used COVID-19 vaccine in the world, with 943 million doses delivered globally. In July, Sinovac signed advanced purchase agreements with GAVI to supply COVAX with 50 million doses in the third quarter of 2021 and up to a total of 380 million doses by the first half of 2022.

Asia

In January, Azerbaijan launched its vaccination campaign with CoronaVac. It purchased 4 million doses from Turkey and 5 million doses from China.

In May, Armenia received 100,000 doses from China.

In February, Cambodia approved Coronavac for emergency use and started vaccinations in March. By July, the country had received 10.5 million doses.

In October, Saudi Arabia signed an agreement to distribute CoronaVac to 7,000 healthcare workers, after conducting Phase III trials with the Saudi Arabian National Guard.

In November, Turkey signed a contract to buy 50 million doses of CoronaVac. Turkey approved emergency use on 13 January and President Recep Tayyip Erdoğan received his first dose at Ankara City Hospital. In February, Turkey signed a deal for another 50 million doses for a total of 100 million doses. By March 10.7 million doses had been administered, and 852 of the 1.3 million people who had received both doses were later diagnosed with the disease. 53 were hospitalized, but none of those hospitalized were intubated or died.

In December, Hong Kong ordered 7.5 million doses of CoronaVac. The vaccination campaign with CoronaVac began on 26 February.

By December 2020, Indonesia had signed agreements for 140 million doses of CoronaVac. Indonesia approved emergency use authorization on 11 January and President Joko Widodo received the first shot of the vaccine. By June, Indonesia had received 118.7 million bulk doses.

In January, Malaysia ordered 12 million doses which was approved for emergency use in March. Science, Technology and Innovation Minister Khairy Jamaluddin received the first dose as part of the vaccination campaign.

In March, Kazakhstan ordered 3 million doses, of which 500,000 doses arrived in June and has been approved for use by the Ministry of Health.

In May, Oman received its first batch of the vaccine.

In April, Pakistan granted emergency use authorization for CoronaVac and received 14.5 million doses by July.

In January, the Philippines announced the country had secured 25 million doses. The vaccine was approved on 22 February but not for all health workers as it had lower efficacy when used with health workers compared to healthy individuals aged 18–59. The first 600,000 doses of CoronaVac arrived on 28 February, and the country had received 7.5 million doses by June.

Singapore signed advance purchase agreements for CoronaVac. In February, the first doses arrived and in June it was approved for use under the Special Access Route.

In May, Tajikistan's Ministry of Health announced it would receive 150,000 doses.

In February, Thailand approved emergency use and started its vaccination program on 27 February. As of June, Thailand had received 10.5 million doses.

In May 2021, Georgia began vaccinations with CoronaVac, for which it received 1 million doses by July.

In May 2021, Turkmenistan received a delivery of CoronaVac.

In May 2021, AKIPress reported Uzbekistan plans to use CoronaVac.

In October 2021, Singapore included CoronaVac in its National Vaccination Programme for people aged 18 and over who are ineligible for mRNA vaccines due to allergies or serious adverse reactions after the first dose.

Africa

In March, Benin received 203,000 doses of CoronaVac and started vaccinations on 29 March prioritizing healthcare workers, people over 60, and those with co-morbidities.

In April, Botswana received 200,000 doses of CoronaVac as a donation and purchased an additional 200,000 doses to be used in the vaccination program.

In March, Djibouti received 300,000 doses of CoronaVac.

In April, Egypt approved emergency use of CoronaVac.

In April, Guinea received 300,000 doses of CoronaVac which it had purchased.

In April, Libya received 150,000 doses of CoronaVac from Turkey.

In April, Somalia received 200,000 doses of CoronaVac.

In July, South Africa approved CoronaVac for emergency use, and was expected to receive 2.5 million doses shortly.

In April, Togo received 200,000 doses of CoronaVac.

In March, Tunisia's Ministry of Health approved marketing authorization for CoronaVac and the first 200,000 doses arrived on 25 March.

In March, Zimbabwe approved emergency use and the first 1 million doses arrived on 30 March.

Europe

In March, Albania launched its vaccination campaign using mainly CoronaVac, a week after securing 1 million doses from Turkey.

By June, Northern Cyprus received 190,000 doses donated by Turkey.

In March, Bosnia received 30,000 doses donated by Turkey.

In June, North Macedonia received 30,000 doses donated by Turkey and another 500,000 doses it purchased.

In March, Ukraine granted approval for use of CoronaVac. Ukrainian Pharmaceutical Company Lekhim has an agreement to deliver 5 million doses. 1.7 million doses had been delivered by June.

In April, Moldova purchased 400,000 doses of CoronaVac.

South America

In Brazil, São Paulo governor João Doria signed a $90 million contract with Sinovac in September to receive the initial 46 million doses of CoronaVac. The price for CoronaVac was announced to be US$10.3 (about R$59). In January, Brazil announced it would obtain 100 million total doses. On 17 January, Brazil's health regulatory agency Anvisa approved emergency use of CoronaVac. In early February, Brazil said it intends to buy an additional 30 million doses on top of existing 100 million doses. A total of 39.7 million doses had been delivered by early April.

In October, Chile signed an agreement to purchase 20 million doses of CoronaVac which was approved for emergency use on 20 January. By early March, the country had received 10 million doses of CoronaVac and had vaccinated 4.1 million people.

In February, Colombia had purchased 5 million doses and was in talks for an additional 5 million doses, which had been approved for emergency use on 5 February.

In February, Ecuador signed a deal for 2 million doses which was approved for emergency use, with the first 1 million doses arrived in early April.

In March, Paraguay received a donation of 20,000 doses from Chile. Paraguay began vaccinations with CoronaVac on 10 March.

In January, Uruguay purchased 1.75 million doses, of which the first 192,000 doses arrived on 25 February and vaccinations started on 1 March.

North America

By June 2021, Dominican Republic had received 7.8 million doses of an order for 10 million doses.

In March 2021, El Salvador received 1 million doses of a total 2 million dose order for CoronaVac. The immunization campaign was initially focused on teachers, health professionals, firefighters, police, and military personnel. The first doses were provided to public school teachers beginning on March 30, with rollout expanding to private school teachers shortly after. Vaccination of the general public was planned for April 15, after the vaccination of the priority groups.

In February 2021, Mexico approved emergency use of CoronaVac. The country had ordered 20 million doses by March 2021, of which 7 million had been received by May.

Oceania

In March, Fiji said it would be receiving a donation of CoronaVac.

Controversies

China state media propaganda

In January 2021, as part of a misinformation campaign, multiple Chinese state and CCP-affiliated media outlets, including CGTN and the Global Times, have touted CoronaVac and Chinese vaccines as "relatively safer due to their mature technology". Pushing back against concerns of CoronaVac efficacy over the lack of transparency over releasing test results, China state media have raised doubts about the efficacy of the Pfizer–BioNTech vaccine, calling for an investigation into the deaths of elderly people in Norway and Germany after receiving the vaccine. According to Reuters, the reports made allegations of "deliberately downplaying the deaths" and "using propaganda power to promote the Pfizer vaccine and smearing Chinese vaccines".

According to a Ming Pao report published on 21 March 2022, of the 1,486 who died of COVID-19 after receiving at least one dose, 1,292 of them or 87%—had gotten the Sinovac vaccine. The Centre for Health Protection's Chuang Shuk-kwan said that the Ming Pao report was inaccurate and has defended CorovaVac, saying "The issue is not about which jab offers more protection. The most important thing is whether you get vaccinated." Earlier in February 2022, health authorities refused to disclose data on which COVID-19 vaccine had been taken by Omicron patients, claiming the information "was not readily available." Hong Kong government data showed CoronaVac to be the preferred vaccine among those aged 70 and over, in part because some elderly care homes only offer this vaccine. However, CoronaVac's limited effectiveness compared to the BioNTech vaccine, along with the zero-COVID strategy, have been regarded as factors behind Hong Kong's spiking cases as of March 2022.

Politicization

CoronaVac has been championed by the governor of São Paulo, João Doria. A political showdown began in October 2020, when Bolsonaro vetoed a deal between the Brazilian health ministry and the São Paulo government for the purchase of 46 million doses of the vaccine. After Instituto Butantan announced CoronaVac's efficacy rate, Bolsonaro mocked the vaccine's effectiveness against COVID-19.

In March 2021, the Paraná Pesquisas opinion polling institute found that the vaccines preferred by Brazilians are CoronaVac and the Oxford–AstraZeneca vaccine, chosen by 23.6% and 21.2% of Brazilians interviewed, respectively, against 11.3% of those who would prefer the Pfizer–BioNTech vaccine. During the pandemic parliamentary inquiry in Brazil, senators have expressed that anti-China rhetoric has contributed to delaying access to vaccines in Brazil.

Delays in releasing results

On 23 December 2020, researchers in Brazil said the vaccine was more than 50% effective, but withheld full results at Sinovac's request, raising questions about transparency as it was the third delay in releasing results from the trials. Scientists said the lack of transparency risked damaging CoronaVac's credibility.

U.S. disinformation campaign

The #ChinaAngVirus disinformation campaign (English: #ChinaIsTheVirus) was a covert Internetanti-vaccination propaganda and disinformation campaign conducted by the United States Department of Defense at the height of the COVID-19 pandemic from the spring of 2020 to the spring of 2021, to dissuade Filipino, Central Asian, and Middle Eastern citizens from receiving Sinovac Biotech's CoronaVac vaccine and from using other Chinese COVID-19 medical supplies. The propaganda campaign used at least 300 fake accounts on Twitter, Facebook, Instagram, and other social media websites meant to look like local internet users.