who took the Pfizer-BioNTech vaccine. Variants In the following tables, a vaccine is generally considered effective if the estimate is ≥50% with a >30% lower limit of the 95% confidence interval. Effectiveness is generally expected to slowly decrease over time. In the elderly A test-negative case-control study from 17 January to 29 April 2021 in the state of São Paulo, during which 86% of the collected genotype isolates were of the Gamma variant, with 43,774 participants aged 70 years or older, found an effectiveness after two doses of against symptomatic disease, against hospitalization and against death. After a single dose, the effectiveness was only against symptomatic disease, against hospitalization and against death, highlighting the importance of receiving the second dose. The study also found that effectiveness against symptomatic disease decreased with increasing age: Preliminary data from a large effectiveness study in Brazil with 61 million individuals from 18 January to 30 June 2021, when the Gamma variant was dominant in the country, indicate that effectiveness is markedly reduced in those aged 90 or older, attributable to immunosenescence: 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 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 , 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