should be included in the vaccine. manufacturing pharmaceutical company união quimica started production of sputnik v in brazil in january 2021 large quantities of both adenoviruses are produced by hek 293 cells that have the e1 gene necessary for viral replication. rarely, ad5 can acquire the e1 gene from the hek 293 cells, restoring its ability to replicate. gamaleya has set an acceptable limit of 5,000 replicating virus particles per vaccine dose, and quality control documents state that tested batches contain less than 100 replicating virus particles per dose. the production of the frozen liquid formulation was developed for large-scale use, it is cheaper and easier to manufacture. the production of the freeze-dried formulation takes much more time and resources, although it is more convenient for storage and transportation. it was developed with vaccine delivery to hard-to-reach regions of russia in mind. according to russian media, the mass production of the gam-covid-vac was launched by 15 august. by that moment, the russian federation has already received applications from 20 countries for the supply of 1 billion doses of vaccine. three facilities were able to produce about a million doses per month at each with a potential doubling of capacity by winter. by the end of 2020, gamaleya research institute's production, according to an interview with the organization's spokesperson, was planned to produce 3–5 million doses. as of march 2021, the russian direct investment fund (rdif) has licensed production in india, china, south korea and brazil. in the eu, rdif has signed production agreements. by the end of march 2021 rdif anticipates 33 million doses will have been manufactured in russia, less than 5% of which will have been exported. an agreement for the production of over 100 million doses of vaccine in india was made with dr. reddy's laboratories, which on 11 january 2021 submitted mid-stage trial data to the indian regulator and recommended moving onto late-stage trials. the rdif announced plans to sell 100 million doses to india, 35 million to uzbekistan, and 32 million to mexico, as well as 25 million each to nepal and egypt. in india, the first dose of sputnik v vaccine was administered on 14 may 2021 at hyderabad. argentina became the first latin american country to produce it. large-scale production started in june 2021. as of 31 december 2021 277 million doses were manufactured, mostly (265 million) in russia. on 28 february 2022, as a result of the 2022 russian invasion of ukraine, the united states placed rdif and its chief executive on its list of sanctioned russian entities and people. the european union, ukraine, united kingdom and australia followed later in february and in march. this significantly reduces vaccine's future commercial prospects. resale controversy under a resale arrangement, the russian direct investment fund (rdif) offered abu dhabi-based firm, aurugulf health investments the exclusive rights to sell the sputnik v coronavirus vaccine. according to media reports, the vaccine was intended to be sold to a host of countries at huge premiums. as per documents reviewed by the moscow times, emirati sheikh ahmed dalmook al-maktoum, a dubai royal, worked as the middleman for reselling millions of sputnik v vaccine doses to countries in dire need of covid-19 vaccine at a higher premium. corporate registry data showed that one of the two entities controlling aurugulf is royal group, a conglomerate headed by uae national security advisor, sheikh tahnoon bin zayed al-nahyan. acquired documents, interviews with officials and buyer data showed that countries like pakistan, guyana, which were on the receiving end of the vaccine from the uae, were coerced to pay more than double the price advertised by russia. the same deal was further used for reselling 1 million sputnik v vaccine doses by the emirati royal sheikh ahmed dalmook al-maktoum to kenya for huge mark-ups. however, the deal eventually failed as nairobi learnt of the first shipment consisting of 75,000 doses not coming directly from russia. history package and vial for the first dose the gam-covid-vac vaccine was developed by a cellular microbiologists team of the government-backed gamaleya research institute of epidemiology and microbiology. the group was led by md and ras associate member denis logunov, who also worked on vaccines for the ebolavirus and the mers-coronavirus. in may 2020, the gamaleya research institute of epidemiology and microbiology announced that it had developed the vaccine without serious side effects. by august 2020, phases i and ii of two clinical trials (involving 38 patients each) were completed. only one of them used the formulation which later obtained marketing authorization under limited conditions. this vaccine was given the trade name "sputnik v", after the world's first artificial satellite. during preclinical and clinical trials, 38 participants who received one or two doses of the gam-covid-vac vaccine had produced antibodies against sars-cov-2's spike protein, including potent neutralizing antibodies that inactivate viral particles. on 11 august 2020, the russian minister of health mikhail murashko announced at a government briefing with the participation of president vladimir putin regulatory approval of the vaccine for widespread use. the state registration of the vaccine was carried out "conditionally" with post-marketing measures according to the decree of the government of the russian federation. the registration certificate for the vaccine stated that it could not be used widely in russia until 1 january 2021, and before that, it may be provided to "a small number of citizens from vulnerable groups", such as medical staff and the elderly, according to a ministry of health spokesperson. the license under register number no. лп-006395 (lp-006395) was issued on 11 august by the russian ministry of health. although the announcement was made even before the vaccine candidate had been entered into phase iii trials, the practice of marketing authorization "on conditions" also exists in other countries. on 26 august, certificate no. лп-006423 (lp-006423) was issued for the lyophilized formulation "gam-covid-vac-lyo". on 12 june 2021, developers announced that they had developed and tested a nasal vaccine for children aged 8 to 12, with no side effects found, and that they expected to release it on 15 september 2021. phase i–ii a phase i safety trial began on 18 june 2020. on 4 september 2020, data on 76 participants in a phase i–ii trial were published, indicating preliminary evidence of safety and an immune response. the results were challenged by international vaccine scientists as being incomplete, suspicious, and unreliable when identical data were reported for many of the trial participants, but the authors responded that there was a small sample size of nine, and the measured results of titration could only take discrete values (800, 1600, 3200, 6400). coupled with the observation that values tended to reach a plateau after three to four weeks, they contend that it is not unlikely that several participants would show identical results for days 21 to 28. phase iii sputnik v, efficacy for different conditions. the error bars indicate the confidence interval containing the efficacy with 95% probability in early november 2020, israel hadassah medical center director-general zeev rotstein stated that hadassah's branch in moscow's skolkovo innovation center was collaborating on a phase iii clinical trial. the ongoing phase iii study is a randomised, double-blind, placebo-controlled, multi-centre clinical trial involving 40,000 volunteers in moscow, and is scheduled to run until may 2021. in 2020–2021, phase iii clinical studies were also being conducted in belarus, uae, india, kazakhstan and venezuela. on april 13, 2021, india's health ministry said its drug regulator had found that safety and immunogenicity data from a local trial of sputnik v coronavirus vaccine was comparable to that of a late-stage trial done in russia. variants in may 2021, a study by researchers of the national university of córdoba, argentina, found that the vaccine produced antibodies capable of neutralizing the gamma variant. a study in argentina found that neutralization is maintained against alpha and lambda and reduced against gamma. the degree of reduction, however, does not necessarily imply reduced protection. a small study of 12 serum samples found that antibodies from the vaccine effectively neutralize the alpha variant, with moderately reduced neutralization against the e484k substitution (median 2.8 fold reduction). however, neutralization of the beta variant was markedly reduced (median 6.1 fold reduction). authorizations full authorization emergency authorization authorization expired allowed for travel rejected