in previously vaccinated healthy elderly adults.sep 2021–nov 2022, united kingdom preclinical unnamed dreamtec limited hong kong subunit phase i (30)development of a covid19 oral vaccine consisting of bacillus subtilis spores expressing and displaying the receptor binding domain of spike protein of sars-cov2.apr–dec 2021, hong kong preclinical almansour-001 imam abdulrahman bin faisal university, icon plc ireland, saudi arabia dna phase i (30)single center, randomized, observer blind, dosage finding.feb–jul 2022, ireland, saudi arabia preclinical unnamed north's academy of medical science medical biology institute north korea subunit (spike protein with angiotensin-converting enzyme 2) phase i–ii (?)jul 2020, north korea preclinical vabiotech covid-19 vaccine vaccine and biological production company no. 1 (vabiotech) vietnam subunit preclinicalawaited for the conduct on phase i trial. ? ino-4802 inovio united states dna preclinicalawaited for the conduct on phase i/ii trials. ? bangavax (bancovid)globe biotech ltd. of bangladesh bangladesh rna preclinicalawaiting for approval from bangladesh government to conduct the first clinical trial. ? unnamed indian immunologicals, griffith university australia, india attenuated preclinical ? epv-cov-19 epivax united states subunit (t cell epitope-based protein) preclinical ? unnamed intravacc netherlands subunit preclinical ? curevac–gsk covid-19 vaccine curevac, gsk germany, united kingdom rna preclinical ? dyai-100 sorrento therapeutics, dyadic international, inc. united states subunit preclinical ? unnamedministry of health (malaysia), malaysia institute of medical research malaysia, universiti putra malaysia malaysia rna preclinical ? curevac covid-19 vaccine (cvncov)curevac, cepi germany rna (unmodified rna) terminated (44,433)phase 2b/3 (39,693): multicenter efficacy and safety trial in adults.phase 3 (2,360+180+1,200+1,000=4,740): randomized, placebo-controlled, multicenter, some observer-blinded, some open-labeled.nov 2020 – jun 2022, argentina, belgium, colombia, dominican republic, france, germany, mexico, netherlands, panama, peru, spain phase i–ii (944)phase i (284): partially blind, controlled, dose-escalation to evaluate safety, reactogenicity and immunogenicity.phase iia (660):partially observer-blind, multicenter, controlled, dose-confirmation.jun 2020 – oct 2021, belgium (phase i), germany (phase i), panama (phase iia), peru (phase iia) emergency (2) eu switzerland corvax12oncosec medical, providence health & services united states dna terminated (36)open-label, non-randomized, parallel assignment study to evaluate the safety of prime & boost doses with/without the combination of electroporated il-12p70 plasmid in 2 age groups: 18-50 years-old and > 50 years-old.dec 2020 – jul 2021, united states preclinical sanofi–translate bio covid-19 vaccine (mrt5500)sanofi pasteur and translate bio france, united states rna terminated (415)interventional, randomized, parallel-group, sequential study consisting of a sentinel cohort followed by the full enrollment cohort. the sentinel cohort is an open-label, step-wise, dose-ranging study to evaluate the safety of 3 dose levels with 2 vaccinations. the full enrollment cohort is a quadruple-blinded study of safety and immunogenicity in 2 age groups, with half receiving a single injection, and the other half receiving 2 injections.mar 2021 – sep 2021, honduras, united states, australia preclinical adcovidaltimmune inc. united states viral vector terminated (180)double-blind, randomized, placebo-controlled, first-in-human.feb 2021 – feb 2022, united states preclinical lnp-ncovsarnamrc clinical trials unit at imperial college london united kingdom rna terminated (105)randomized trial, with dose escalation study (15) and expanded safety study (at least 200)jun 2020 – jul 2021, united kingdom ? tmv-083institut pasteur france viral vector terminated (90)randomized, placebo-controlled.aug 2020 – jun 2021, belgium, france ? sars-cov-2 sclamp/v451uq, syneos health, cepi, seqirus australia subunit (molecular clamp stabilized spike protein with mf59) terminated (120)randomised, double-blind, placebo-controlled, dose-ranging.false positive hiv test found among participants.jul–oct 2020, brisbane ? v590 and v591/mv-sars-cov-2 merck & co. (themis bioscience), institut pasteur, university of pittsburgh's center for vaccine research (cvr), cepi united states, france vesicular stomatitis virus vector / measles virus vector terminatedin phase i, immune responses were inferior to those seen following natural infection and those reported for other sars-cov-2/covid-19 vaccines. latest phase with published results. phase i–iia in south korea in parallel with phase ii–iii in the us homologous prime-boost vaccination in july 2021, the u.s. food and drug administration (fda) and the centers for disease control and prevention (cdc) issued a joint statement reporting that a booster dose is not necessary for those who have been fully vaccinated. in august 2021, the fda and the cdc authorized the use of an additional mrna vaccine dose for immunocompromised individuals. the authorization was extended to cover other specific groups in september 2021. in october 2021, the fda and the cdc authorized the use of either homologous or heterologous vaccine booster doses. heterologous prime-boost vaccination the world health organization (who) defines heterologous prime-boost immunization as the "administration of two different vectors or delivery systems expressing the same or overlapping antigenic inserts." a heterologous scheme can sometimes be more immunogenic than some homologous schemes. in october 2021, the fda and the cdc authorized the use of either homologous or heterologous vaccine booster doses. some experts believe that heterologous prime-boost vaccination courses can boost immunity, and several studies have begun to examine this effect. despite the absence of clinical data on the efficacy and safety of such heterologous combinations, canada and several european countries have recommended a heterologous second dose for people who have received the first dose of the oxford–astrazeneca vaccine. in february 2021, the oxford vaccine group launched the com-cov vaccine trial to investigate heterologous prime-boost courses of different covid-19 vaccines. as of june 2021, the group is conducting two phase ii studies: com-cov and com-cov2. in com-cov, the two heterologous combinations of the oxford–astrazeneca and pfizer–biontech vaccines were compared with the two homologous combinations of the same vaccines, with an interval of 28 or 84 days between doses. in com-cov2, the first dose is the oxford–astrazeneca vaccine or the pfizer vaccine, and the second dose is the moderna vaccine, the novavax vaccine, or a homologous vaccine equal to the first dose, with an interval of 56 or 84 days between doses. a study in the uk is evaluating annual heterologous boosters by randomly combining the following vaccines: oxford–astrazeneca, pfizer–biontech, moderna, novavax, vla2001, curevac, and janssen. on 16 december, who recommendations on heterologous vaccinations suggested a general trend of increased immunogenicity when one of the doses is of an mrna vaccine, particularly as the last dose. the immunogenicity of a homologous mrna course is roughly equivalent to a heterologous scheme involving a vector vaccine and an mrna vaccine. however, the who has emphasized the need to address many evidence gaps in heterologous regimens, including duration of protection, optimal interval between doses, influence of fractional dosing, effectiveness against variants and long-term safety. heterologous second dose regimes in clinical trial first dose second dose schedules current phase (participants), periods and locations oxford–astrazenecapfizer–biontech oxford–astrazenecapfizer–biontech days 0 and 28days 0 and 84 phase ii (820)feb–aug 2021, united kingdom sputnik light oxford–astrazenecamodernasinopharm bibp phase ii (121)feb–aug 2021, argentina oxford–astrazenecapfizer–biontech oxford–astrazenecapfizer–biontechmodernanovavax days 0 and 56–84 phase ii (1,050)mar 2021 – sep 2022, united kingdom convidecia zf2001 days 0 and 28days 0 and 56 phase iv (120)apr–dec 2021, china oxford–astrazeneca pfizer–biontech days 0 and 28 phase ii (676)apr 2021 – apr 2022, spain oxford–astrazenecapfizer–biontechmoderna pfizer–biontechmoderna days 0 and 28days 0 and 112 phase ii (1,200)may 2021 – mar 2023, canada pfizer–biontechmoderna pfizer–biontechmoderna days 0 and 42 phase ii (400)may 2021 – jan 2022, france oxford–astrazeneca pfizer–biontech days 0 and 28days 0 and 21–49 phase ii (3,000)may–dec 2021, austria janssen pfizer–biontechjanssenmoderna days 0 and 84 phase ii (432)jun 2021 – sep 2022, netherlands heterologous booster dose regimes in clinical trial initial course booster dose interval current phase (participants), periods and locations coronavac (2 doses) coronavacpfizer–biontechoxford–astrazeneca 19 weeks or more phase iv (2,017,878)aug–nov 2021, chile efficacy cumulative incidence curves for symptomatic covid-19 infections after the first dose of the pfizer–biontech vaccine (tozinameran) or placebo in a double-blind clinical trial. (red: placebo; blue: tozinameran) vaccine efficacy is the reduction in risk of getting the disease by vaccinated participants in a controlled trial compared with the risk of getting the disease by unvaccinated participants. an efficacy of 0% means that the vaccine does not work (identical to placebo). an efficacy of 50% means that there are half as many cases of infection as in unvaccinated individuals. covid-19 vaccine efficacy may be adversely affected if the arm is held improperly or squeezed so the vaccine is injected subcutaneously instead of into the muscle. the cdc guidance is to not repeat doses that are administered subcutaneously. it is not straightforward to compare the efficacies of the different vaccines because the trials were run with different populations, geographies, and variants of the virus. in the case of covid-19 prior to the advent of the delta variant, it was thought that a vaccine efficacy of 67% may be enough to slow the pandemic, but the current vaccines do not confer sterilizing immunity, which is necessary to prevent transmission. vaccine efficacy reflects disease prevention, a poor indicator of transmissibility of sars‑cov‑2 since asymptomatic people can be highly infectious. the us food and drug administration (fda) and the european medicines agency (ema) set a cutoff of 50% as the efficacy required to approve a covid-19 vaccine, with the lower limit of the 95% confidence interval being greater than 30%. aiming for a realistic population vaccination coverage rate of 75%, and depending on the actual basic reproduction number, the necessary effectiveness of a covid-19 vaccine is expected to need to be at least 70% to prevent an epidemic and at least 80% to extinguish it without further measures, such as social distancing. the observed substantial efficacy of certain mrna vaccines even after partial (1-dose) immunization indicates a non-linear dose-efficacy relation already seen in the phase i-ii study. it suggests that personalization of the vaccine dose (regular dose to the elderly, reduced dose to the healthy young, additional booster dose to the immunosuppressed) might allow accelerating vaccination campaigns in settings of limited supplies, thereby shortening the pandemic, as predicted by pandemic modeling. ranges below are 95% confidence intervals unless indicated otherwise, and all values are for all participants regardless of age, according to the references for each of the trials. by definition, the accuracy of the estimates without an associated confidence interval is unknown publicly. efficacy against severe covid-19 is the most important, since hospitalizations and deaths are a public health burden whose prevention is a priority. authorized and approved vaccines have shown the following efficacies: covid-19 vaccine efficacy () vaccine efficacy by severity of covid-19 trial location refs mild or moderate severe without hospitalization or death severe with hospitalization or death oxford–astrazeneca 81% (60–91%) 100% (97.5% ci, 72–100%) 100% multinational 74% (68–82%) 100% 100% united states pfizer–biontech 95% (90–98%) 66% (−125 to 96%) multinational 95% (90–98%) not reported not reported united states janssen 66% (55–75%) 85% (54–97%) 100% multinational 72% (58–82%) 86% (−9 to 100%) 100% united states 68% (49–81%) 88% (8–100%) 100% brazil 64% (41–79%) 82% (46–95%) 100% south africa moderna 94% (89–97%) 100% 100% united states sinopharm bibp 78% (65–86%) 100% 100% multinational 79% (66–88%) not reported 79% (26–94%) multinational sputnik v 92% (86–95%) 100% (94–100%) 100% russia coronavac 51% (36–62%) 84% (58–94%) 100% (56–100%) brazil 84% (65–92%) 100% 100% (20–100%) turkey covaxin 78% (65–86%) 93% (57–100%) india sputnik light 79% not reported not reported russia convidecia 66% 91% not reported multinational sinopharm wibp 73% (58–82%) 100% 100% multinational abdala 92% (86–96%) not reported not reported cuba soberana 02 71% (59–79%) 63% not reported cuba 67% (59–79%) 97% 95% iran soberana 02 and soberana plus 92% (87–96%) 100% not reported cuba novavax 90% (75–95%) 100% 100% united kingdom 60% (20–80%) 100% 100% south africa 90% (83–95%) not reported not reported united states not reported not reported mexico curevac 48% not reported not reported multinational zycov-d 67% not reported not reported india epivaccorona 79% not reported not reported russia zf2001 82% not reported not reported multinational scb-2019 67% (54–77%) not reported not reported multinational covlp 71% (59–80%) not reported not reported multinational sanofi–gsk covid-19 vaccine 58% (27–77%) not reported not reported multinational mild symptoms: fever, dry cough, fatigue, myalgia, arthralgia, sore throat, diarrhea, nausea, vomiting, headache, anosmia, ageusia, nasal congestion, rhinorrhea, conjunctivitis, skin rash, chills, dizziness. moderate symptoms: mild pneumonia. severe symptoms without hospitalization or death for an individual, are any one of the following severe respiratory symptoms measured at rest on any time during the course of observation (on top of having either pneumonia, deep vein thrombosis, dyspnea, hypoxia, persistent chest pain, anorexia, confusion, fever above 38 °c (100 °f)), that however were not persistent/severe enough to cause hospitalization or death: any respiratory rate ≥30 breaths/minute, heart rate ≥125 beats/minute, oxygen saturation (spo2) ≤93% on room air at sea level, or partial pressure of oxygen/fraction of inspired oxygen (pao2/fio2)