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Single-dose Oxford–AstraZeneca COVID-19 vaccine followed by a 12-week booster

2021; Elsevier BV; Volume: 397; Issue: 10277 Linguagem: Inglês

10.1016/s0140-6736(21)00528-6

1474-547X

Ivan Fan‐Ngai Hung, Gregory A. Poland,

Vaccine Coverage and Hesitancy

Vaccines to prevent COVID-19 infection are crucial for an effective global pandemic response. In The Lancet, Merryn Voysey and colleagues1Voysey M Costa Clemens SA Madhi SA et al.Single dose administration and the influence of the timing of the booster dose on immunogenicity and efficacy of ChAdOx1 nCoV-19 (AZD1222) vaccine: a pooled analysis of four randomised trials.Lancet. 2021; 397: 881-891Summary Full Text Full Text PDF PubMed Scopus (793) Google Scholar report the updated primary efficacy results for the Oxford–AstraZeneca ChAdOx1 nCoV-19 (AZD1222) vaccine from three single-blind, randomised controlled trials in the UK and Brazil and one double-blind study in South Africa.2Folegatti PM Ewer KJ Aley PK et al.Safety and immunogenicity of the ChAdOx1 nCoV-19 vaccine against SARS-CoV-2: a preliminary report of a phase 1/2, single-blind, randomised controlled trial.Lancet. 2020; 396: 467-478Summary Full Text Full Text PDF PubMed Scopus (1749) Google Scholar, 3Ramasamy MN Minassian AM Ewer KJ et al.Safety and immunogenicity of ChAdOx1 nCoV-19 vaccine administered in a prime-boost regimen in young and old adults (COV002): a single-blind, randomised, controlled, phase 2/3 trial.Lancet. 2021; 396: 1979-1993Summary Full Text Full Text PDF PubMed Scopus (1058) Google Scholar, 4Voysey M Clemens SAC Madhi SA et al.Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: an interim analysis of four randomised controlled trials in Brazil, South Africa, and the UK.Lancet. 2021; 397: 99-111Summary Full Text Full Text PDF PubMed Scopus (3260) Google Scholar The ChAdOx1 nCoV-19 vaccine was granted emergency use authorisation in adults by the UK Medicines and Healthcare products Regulatory Agency5Medicines and Healthcare products Regulatory AgencyRegulatory approval of COVID-19 vaccine AstraZeneca.https://www.gov.uk/government/publications/regulatory-approval-of-covid-19-vaccine-astrazenecaDate: Jan 28, 2021Date accessed: February 18, 2021Google Scholar in December, 2020. A subsequent report, based on an interim analysis of four randomised controlled trials done in Brazil, South Africa, and the UK,4Voysey M Clemens SAC Madhi SA et al.Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: an interim analysis of four randomised controlled trials in Brazil, South Africa, and the UK.Lancet. 2021; 397: 99-111Summary Full Text Full Text PDF PubMed Scopus (3260) Google Scholar suggested an overall vaccine efficacy of 70·4% (95·8% CI 54·8–80·6), with a higher efficacy of 90% (95% CI 67·4–97·0) in those who received a low dose (2·2 × 1010 viral particles per dose) followed by a standard dose (5 × 1010 viral particles per dose), and a vaccine efficacy of 62·1% (95% CI 41·0–75·7) in those who received two standard doses (4 weeks apart). As a result of these interim data, and to achieve the greatest health benefit rapidly, the UK Government decided on a policy of administering as many first doses as possible and delaying the second dose of the ChAdOx1 nCoV-19 vaccine until 12 weeks after the first dose.6UK Department of Health and Social CareStatement from the UK Chief Medical Officers on the prioritisation of first doses of COVID-19 vaccines.https://www.health-ni.gov.uk/news/statement-uk-chief-medical-officers-prioritisation-first-doses-covid-19-vaccinesDate: Dec 30, 2020Date accessed: February 18, 2021Google Scholar, 7UK Department of Health and Social CareOxford University/AstraZeneca vaccine authorised by UK medicines regulator.https://www.gov.uk/government/news/oxford-universityastrazeneca-vaccine-authorised-by-uk-medicines-regulatorDate: Dec 30, 2020Date accessed: February 18, 2021Google Scholar Although this policy was criticised, the latest results reported by Voysey and colleagues provide a necessary evidence-based justification for the decision.1Voysey M Costa Clemens SA Madhi SA et al.Single dose administration and the influence of the timing of the booster dose on immunogenicity and efficacy of ChAdOx1 nCoV-19 (AZD1222) vaccine: a pooled analysis of four randomised trials.Lancet. 2021; 397: 881-891Summary Full Text Full Text PDF PubMed Scopus (793) Google Scholar The study is based on an updated analysis of 17 178 participants (9696 [56·4%] were women, 12 975 [75·5%] were white, and 14 413 [83·9%] were aged 18–55 years, 1792 [10·4%] aged 56–69 years, and 973 [5·7%] aged 70 years or older) from the four trials.2Folegatti PM Ewer KJ Aley PK et al.Safety and immunogenicity of the ChAdOx1 nCoV-19 vaccine against SARS-CoV-2: a preliminary report of a phase 1/2, single-blind, randomised controlled trial.Lancet. 2020; 396: 467-478Summary Full Text Full Text PDF PubMed Scopus (1749) Google Scholar, 3Ramasamy MN Minassian AM Ewer KJ et al.Safety and immunogenicity of ChAdOx1 nCoV-19 vaccine administered in a prime-boost regimen in young and old adults (COV002): a single-blind, randomised, controlled, phase 2/3 trial.Lancet. 2021; 396: 1979-1993Summary Full Text Full Text PDF PubMed Scopus (1058) Google Scholar, 4Voysey M Clemens SAC Madhi SA et al.Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: an interim analysis of four randomised controlled trials in Brazil, South Africa, and the UK.Lancet. 2021; 397: 99-111Summary Full Text Full Text PDF PubMed Scopus (3260) Google Scholar The pooled results from these trials (including participants who received two standard doses and those who received a low dose followed by a standard dose) showed an overall vaccine efficacy against symptomatic COVID-19 more than 14 days after the second dose of 66·7% (95% CI 57·4–74·0). Vaccine efficacy was 63·1% (51·8–71·7) in those who received two standard doses and 80·7% (62·1–90·2) in those who received the low dose plus standard dose. Notably, in exploratory analyses, vaccine efficacy after a single standard dose was 76·0% (59·3–85·9) from day 22 to day 90, and antibody levels were maintained during this period with minimal waning. Supporting a longer-interval immunisation strategy, vaccine efficacy was significantly higher at 81·3% (60·3–91·2) after two standard doses given at an interval of 12 weeks or longer, compared with 55·1% (33·0–69·9) when given less than 6 weeks apart. These findings were supported by immunogenicity studies done in participants who were younger than 55 years, showing anti-SARS-CoV-2 spike IgG antibody responses more than two-fold higher in those who had a dose interval of at least 12 weeks than in those who had an interval of less than 6 weeks (geometric mean ratio 2·32 [95% CI 2·01–2·68]). Modelling analyses showed an increase in vaccine efficacy after two standard doses from 55·1% (95% CI 33·0 to 69·9) with an interval of less than 6 weeks to 81·3% (60·3 to 91·2) with an interval of at least 12 weeks. A single standard dose had an efficacy against symptomatic COVID-19 in the first 90 days of 76·0% (59·3 to 85·9), yet provided no protection against asymptomatic infection (vaccine efficacy −17·2% [–248·6 to 60·6]). Notably, efficacy against any nucleic acid amplification test-positive cases, including symptomatic and asymptomatic or unknown cases, was 63·9% (46·0 to 75·9) after a single standard dose, suggesting the possibility of reducing viral transmission. Important study limitations include the fact that these studies were not prospectively designed to establish whether vaccine efficacy would differ by dose interval; therefore, these post-hoc exploratory findings could be biased. Other limitations are that participants were not randomised to dosing interval, only one of the four trials was double-blind, and the single-dose recipients were self-selected. Furthermore, baseline characteristics between the single-dose and two-dose cohorts were substantially different, with an older median age, higher proportion of men and non-white participants, and a smaller proportion of health or social care workers in the two-dose cohort than in the single-dose cohort. Also, worth considering is whether these results would hold up with widespread circulation of more transmissible and lethal viral variants. Overall, the value of this study is in providing evidence that a single dose of the ChAdOx1 nCoV-19 vaccine is highly efficacious in the 90 days after vaccination, that a longer prime-boost interval results in higher vaccine efficacy, and that protection against symptomatic COVID-19 is maintained despite a longer dosing interval. It offers much-needed evidence for the UK policy of extending the dosing interval to 12 weeks and for rapid mass-immunisation campaigns worldwide. Further studies are warranted to assess whether a longer-interval strategy would also offer higher vaccine efficacy against the new variants8Fontanet A Autran B Lina B Kieny MP Karim SSA Sridhar D SARS-CoV-2 variants and ending the COVID-19 pandemic.Lancet. 2021; (published online Feb 11.)https://doi.org/10.1016/S0140-6736(21)00370-6Summary Full Text Full Text PDF PubMed Scopus (387) Google Scholar and could be applicable to other types of COVID-19 vaccines.9Strategic Advisory Group of Experts (SAGE) on Immunization Working Group on COVID-19 vaccinesmRNA vaccines against COVID-19: Pfizer-BioNTech COVID-19 vaccine BNT162b2. World Health Organization, Dec 22, 2020https://apps.who.int/iris/bitstream/handle/10665/338096/WHO-2019-nCoV-vaccines-SAGE_evaluation-BNT162b2-2020.1-eng.pdf?sequence=1&isAllowed=yDate accessed: February 18, 2021Google Scholar, 10Moghadas SM Vilches TN Zhang K et al.Evaluation of COVID-19 vaccination strategies with a delayed second dose.medRxiv. 2021; (published online Jan 29.) (preprint).https://doi.org/10.1101/2021.01.27.21250619Google Scholar, 11Kadire SR Wachter RM Lurie N Delayed second dose versus standard regimen for Covid-19 vaccination.N Engl J Med. 2021; (published online Feb 17.)https://doi.org/10.1056/NEJMclde2101987Crossref PubMed Scopus (52) Google Scholar IFNH is a member of the Advisory Panel on COVID-19 Vaccines for the Government of the Hong Kong Special Administrative Region. GAP receives personal fees from AstraZeneca for consultative advice on COVID-19 vaccine messaging. GAP is the chair of a Safety Evaluation Committee for novel non-COVID investigational vaccine trials being conducted by Merck Research Laboratories. GAP offers consultative advice on non-COVID vaccine development to Merck, Medicago, GlaxoSmithKline, Sanofi Pasteur, Emergent Biosolutions, Dynavax, Genentech, and Genevant Sciences. GAP has offered consultative advice on COVID vaccine study design and safety to Eli Lilly and Company, Janssen Global Services, and AstraZeneca. GAP holds patents related to vaccinia and measles peptide vaccines. GAP has received grant funding from ICW Ventures for preclinical studies on a peptide-based COVID-19 vaccine. Single-dose administration and the influence of the timing of the booster dose on immunogenicity and efficacy of ChAdOx1 nCoV-19 (AZD1222) vaccine: a pooled analysis of four randomised trialsThe results of this primary analysis of two doses of ChAdOx1 nCoV-19 were consistent with those seen in the interim analysis of the trials and confirm that the vaccine is efficacious, with results varying by dose interval in exploratory analyses. A 3-month dose interval might have advantages over a programme with a short dose interval for roll-out of a pandemic vaccine to protect the largest number of individuals in the population as early as possible when supplies are scarce, while also improving protection after receiving a second dose. Full-Text PDF Open Access