PROGRESS the first wave of efficacy data and the first vaccine approvals were not the end of the Progress of the COVID-19 vaccine clinical trial phase for COVID-19 vaccines. Ongoing vaccine trials test the efficacy of effort: viruses, vaccines and variants new vaccines in the face of an evolving virus; furthermore, they increase options versus efficacy, effectiveness and for globally dispersed manufacturing of sufficient vaccine doses for global use and strengthen the data for novel vaccine escape platforms that could be of use in future pandemics. As this is a rapidly moving space, John S. Tregoning , Katie E. Flight, Sophie L. Higham, Ziyin Wang the best way to stay abreast of the vaccine and Benjamin F. Pierce trials is through live documents, such as the COVID-19 vaccine tracker from the London Abstract | Where 2020 saw the development and testing of vaccines against severe School of Hygiene and Tropical Medicine. acute respiratory syndrome coronavirus 2 (SARS-CoV-2) at an unprecedented Within this larger list of ongoing pace, the first half of 2021 has seen vaccine rollout in many countries. In this studies, a smaller number of vaccines are Progress article, we provide a snapshot of ongoing vaccine efficacy studies, as well in phase III clinical trials that are yet to as real-world data on vaccine effectiveness and the impact of virus variants of release data: Inovio (DNA, ClinicalTrials. gov identifier NCT04336410), AnGes concern. Where they have been deployed in a high proportion of the adult (DNA, NCT04655625), ReiThera (gorilla population, the currently approved vaccines have been extremely effective in adenovirus, NCT04791423), the Chinese preventing COVID-19, particularly severe disease. Nonetheless, there are Academy of Medical Sciences (inactivated still significant challenges in ensuring equitable vaccine access around the globe virus, NCT04412538), the Research and lessons that can be learned for controlling this pandemic and for the Institute for Biological Safety Problems, Kazakhstan (QazCovid; inactivated virus, next pandemic. NCT04691908), Shifa (inactivated virus, NCT04526990), the Center for Genetic Fifteen months on from the administration and while transmission levels remain high, Engineering and Biotechnology, Cuba of the first experimental COVID-19 vaccine there is an increased likelihood of vaccine (CIGB-66; peptide, RPCEC00000345), doses to humans in March 2020, there is escape variants evolving. In this Progress Clover (peptide, NCT04672395), COVAXX now a global race against the causative article, we cover recent developments (peptide, NCT04545749), the Finlay virus severe acute respiratory syndrome in COVID-19 vaccines since the start of Institute, Cuba (peptide, RPCEC00000332), coronavirus 2 (SARS-CoV-2) to deploy their deployment in late 2020/early 2021, Sanofi–GlaxoSmithKline (adjuvanted vaccines to control the pandemic1, with including real-world data on vaccine protein, NCT04904549), VECTOR differing levels of vaccine rollout in different effectiveness and the impact of viral variants. (peptide, NCT04780035) and Medicago countries (Our World in Data). Despite (plant-derived virus-like particle, authorization having been granted for The current vaccine landscape NCT04636697). We anticipate that some multiple vaccines, as the ongoing global Data from several phase III vaccine efficacy of the candidate vaccines currently in outbreaks demonstrate, the pandemic is trials were reported at the end of 2020, phase III trials will become available for far from over. Vaccination, in combination leading to the approval and rollout of these wider use in quarters 3 and 4 of 2021, which with non-pharmaceutical interventions, is vaccines. The following organizations have will be important in stemming further waves the best way to control the pandemic. In this reported efficacy data for their vaccines as of the pandemic and increasing vaccination regard, we are fortunate that there is now summarized in Table 1: Pfizer–BioNTech2, rates in lower-income countries. a formidable toolkit of potential vaccines Moderna3, AstraZeneca–University of However, it should also be noted available: of the 322 candidate vaccines that Oxford4, Johnson & Johnson5, Gamaleya6, that some fairly high-profile vaccine have been proposed so far (July 2021), 99 are Sinovac Biotech7, Sinopharm7, Novavax8 programmes may not enter phase III in clinical testing, 25 have reached phase III and Bharat Biotech9. As of 14 June 2021, efficacy studies. In collaboration with efficacy studies and 18 have received some each of these vaccines, except for the IAVI, Merck developed the viral-vectored form of approval for use. However, achieving Novavax vaccine, had been approved for COVID-19 vaccine V590 (REF.10). Merck global vaccine coverage remains a major rollout to adults and, in some cases, to also acquired a second COVID-19 vaccine hurdle; this is not just a matter of equity but adolescents through a range of approval through the buyout of Themis, the is also an important part of the process to processes depending on the region and company responsible for producing the control the virus. SARS-CoV-2 continues regulatory agency. This situation remains V591 (live viral vector) vaccine. However, to evolve under immune selective pressure, fluid, and importantly, the publication of the development of both V590 and V591 626 | OCTOBER 2021 | VOLUME 21 www.nature.com/nri 0123456789();: PROGRESS Table 1 | Reported COVID-19 vaccine efficacy data from phase III trials Vaccine Platform Clinical Total Efficacy End point Eligibility Duration of Circulating Results by manufacturer trial trial measure follow up for genotypes at severity (vaccine name)a regime size phase III trial location and time of trial Pfizer–BioNTech mRNA 2 doses 43,548 95% Symptomatic >16 years old Up to 24 B.1.351, P.1, 100% (BNT162b2)2 (21 days COVID-19 months after B.1.427/B.1.419, effective in apart) and positive second dose P.2 and B.1.526 preventing RT–PCR test (NCT04368728) CDC-defined result severe dis- ease; 95.3% effective in preventing FDA-defined severe disease Moderna mRNA 2 doses 30,420 94% Symptomatic ≥18 years old Up to B.1.427/B.1.429 100% efficacy (mRNA-1273)3 (28 days COVID-19 (12 years old 24 months after and B.1.526 against severe apart) and positive to younger second dose disease RT–PCR test than 18 years (NCT04470427) result (NCT04649151) and 6 months old to younger than 12 years (NCT04796896)) AstraZeneca– Viral 2 doses 17 ,178 55% Symptomatic ≥18 years 24 months B.1.1.7 , 100% efficacy University of vector (<6 weeks COVID-19 old (WHO); after first dose B.1.351, P.1, against Oxford (AZD1222 apart) and positive ≥40 years (NCT04516746) B.1.427/B.1.429, hospitalization (Vaxzevria, 2 doses 81% NAAT result old and not 12 months after P.2, B.1.526 also called pregnant in UK and C.37 (>12 weeks (Pooled second dose Covishield when apart) efficacy (NCT04400838, manufactured by NCT04536051 4 67%) SII under license)) and NCT04516746) Johnson & Johnsonb Viral 1 dose 44,325 66% Symptomatic ≥18 years old 25 months B.1.351, P.1, 85.4% efficacy (Ad26.COV2-S)5,51 vector COVID-19 (NCT04505722) B.1.427/B.1.429, against and positive and 27 months P.2, B.1.526 and severe–critical RT–PCR test (NCT04614948) C.37 disease result after first dose occurring ≥28 days after vaccination Gamaleyab Viral 2 doses 19,866 92% Symptomatic ≥18 years old 6 months No variants No data (Sputnik V)6 vector (21 days COVID-19 after first dose have been available (June apart) and positive (NCT04656613 identified origi- 2021) RT–PCR test and nating from the result NCT04642339) trial locations from the trial start date to the present (June 2021) Bharat Biotechb Viral 2 doses 25,800 78% Symptomatic ≥18 years old 12 months after Phase III trial 100% efficacy (Covaxin)9 vector (28 days COVID-19 (2–18 years old: second dose began on against apart) and positive study ongoing) (NCT04641481); 16 November hospitalization RT–PCR test paediatric 2020 and is result at least cohort followed ongoing in India; 14 days after up for 9 months variants iden- second dose (NCT04918797) tified include B.1.617.2 and B.1.617.1 Sinovac Biotech Inacti- 2 doses 2,300 Multiple Symptomatic, ≥18 years old 12 months P.1 and P.2 51% efficacy (CoronaVac)7 vated (14 days (Chile); studies in virologically after first dose against virus apart; 13,000 different confirmed symptomatic 14 or (Turkey); countries: COVID-19 SARS-CoV-2 28 days 12,688 50.7% occurring infection; apart in (Brazil) (Brazil), from 2 weeks 100% efficacy Chile) 56.5% after the against severe (Chile), 65% second dose disease; (Indonesia), up to 1 year 100% efficacy 78% (Brazil) after the first against hospi- and 91% dose talization from (Turkey) 14 days after second dose NATURE REVIEWS | IMMUNOLOGY VOLUME 21 | OCTOBER 2021 | 627 0123456789();: PROGRESS Table 1 (cont.) | Reported COVID-19 vaccine efficacy data from phase III trials Vaccine Platform Clinical Total Efficacy End point Eligibility Duration of Circulating Results by manufacturer trial trial measure follow up for genotypes at severity (vaccine name)a regime size phase III trial location and time of trial Sinopharm Inacti- 2 doses 45,000 78% Occurrence ≥18 years old 12 months No variants 79% efficacy (BBIBP-CorV)7 vated (21 days of COVID-19 after first dose have been against virus apart) (NCT04510207) identified hospitalization originating from the trial locations during this time (June 2021) Novavaxb Protein 2 doses >15,000 89% Symptomatic ≥18 years old 24 months B.1.1.7 , B.1.351, 100% efficacy (NVX-CoV2373)8,46,65