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Since January 2020 Elsevier Has Created a COVID-19 Resource Centre with Free Information in English and Mandarin on the Novel Coronavirus COVID- 19 Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID- 19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active. Correspondence AZD1222-induced AZD1222 (n=50, median time after 186 [95%] of 195 against B.1.617.2). neutralising antibody first dose 41 days [IQR 30–51]) or Analysis of these data by ordered two doses of AZD1222 (n=63, median logistic regression confirmed vaccine Published Online activity against time after second dose 31 days type was associated with decreased June 28, 2021 https://doi.org/10.1016/ [IQR 19·5–46·0]; appendix p 7). The NAbTs, independent of SARS-CoV-2 SARS-CoV-2 Delta VOC S0140-6736(21)01462-8 median interval between doses was strain, in two-dose vaccine recipients The SARS-CoV-2 B.1.617.2 Delta 63 days (IQR 62·0–69·5). Consistent (p=0·0017; appendix p 4). variant of concern (VOC) continues with our previous findings,3 we included A single dose of AZD1222 generated to drive a sharp increase in COVID-19 a strain with the original spike sequence a broad range of NAb activity against cases in the UK, with a current doubling (Wildtype), a strain with an Asp614Gly Wildtype SARS-CoV-2 (appendix time of 3·5–16 days,1 consistent with mutation isolated during the first wave p 2). Given reports of enhanced NAb previous pandemic waves during of infection in the UK, in 2020 (D614G), responses to VOCs B.1.1.7 and B.1.351 2020–21, and a sustained increase and VOCs B.1.1.7 (Alpha, first detected after a single dose of mRNA vaccines in in the reproduction number (R) to in Kent, England), B.1.351 (Beta, first individuals with previous SARS-CoV-2 1·2–1·4.2 Daily hospital admissions detected in South Africa), and B.1.617.2 infection,4,5 in the absence of concrete and the number of patients requiring (Delta, first detected in India). evidence of previous infection, we mechanical ventilation are now Two doses of AZD1222 generated stratified NAbT by whether participants increasing in both England and NAb activity against the Wildtype reported prior COVID-19 symptoms Scotland, despite the ongoing roll-out strain bearing a spike identical to and found markedly different of widespread vaccination in the UK.1 that encoded by the vaccine in all responses. After a single AZD1222 The ChAdOx1 nCoV-19 (AZD1222, participants (median NAbT IC50=419), dose, participants with prior COVID-19 Oxford–AstraZeneca) vaccine forms the with a 2·1–fold (95% CI 2·0–2·2) symptoms (16 [32%] of 50) had core of the UK’s vaccination programme reduction in median NAbT relative to significantly higher NAbTs against all and the global COVAXX programme. two doses of BNT162b2 (appendix strains than those without prior COVID To determine B.1.617.2 sensitivity p 2). Moreover, median NAbTs symptoms (5·1 × 10⁻⁵≤p≤3·1 × 10⁻⁴). to AZD1222-induced neutralising against all SARS-CoV-2 variants were Since many responses fell outside of antibodies (NAbs) and to compare further reduced relative to BNT162b2: the quantitative limit of detection, this to our previous measurements 2·4-fold (95% CI 2·3–2·6) against stratification of NAbTs was again of NAbs induced by BNT162b2 D614G, 2·4-fold against B.1.1.7 informative. Whereas participants (Pfizer–BioNTech),3 we carried out (2·2–2·5), 2·5-fold (1·3–2·8) against without prior COVID-19 symptoms a second initial analysis of Legacy B.1.351, and 2·5-fold (1·4–2·7) against mostly had quantifiable NAbTs study participants vaccinated with B.1.617.2. Given the low responses against Wildtype (31 [91%] of 34 AZD1222. Legacy was initiated in early against the latter two VOCs, we [95% CI 75–98%]), significantly more 2021 by University College London found that stratification of NAbTs NAb responses against VOCs were Hospitals and the Francis Crick Institute into three groups (IC50 low [<40], below the limit of detection: 22 [65%] in London, UK, to track serological medium [40–256], high [>256]) was of 34 [95% CI 46–80%]) against responses to vaccination during most illustrative: whereas nearly all B.1.1.7; 30 [88%] of 34 [72–96%]) the national COVID-19 vaccination participants had a quantifiable NAbT against B.1.351; and 29 [85%] of programme in prospectively recruited against the D614G and B.1.1.7 variants 34 [68–94%]) against B.1.617.2 healthy staff volunteers. A description (55 [87%] of 63 [95% CI 76–94%]; (2·8 × 10⁻¹⁰≤p≤6·0 × 10⁻⁶; appendix of the methods and clinical cohort are appendix p 2), significantly fewer p 2). Analysis by ordered logistic available in the appendix. The Legacy participants had quantifiable NAbTs regression confirmed that a previous See Online for appendix study was approved by the London against B.1.351 and B.1.617.2 VOCs history of COVID-19 symptoms was Camden and Kings Cross Health after two doses of AZD1222 (38 [60%] associated with increased NAbTs, Research Authority Research and Ethics of 63 [95% CI 47–72%] against B.1.351; independent of SARS-CoV-2 strain, committee (IRAS number 286469) and 39 [62%] of 63 [49–74%] against in single-dose AZD1222 recipients and is sponsored by University College B.1.617.2), relative to the former (p=0.0016; appendix p 4). London Hospitals. two variants (χ² test p<0·0011). This These data, together with our Using a high-throughput live-virus contrasts strongly with our previous previous findings,3 reveal that SARS-CoV-2 neutralisation assay, results, which showed that more than AZD1222 recipients have lower NAbTs we determined NAb titres (NAbTs) 95% of participants had quantifiable than BNT162b2 recipients against Submissions should be against five SARS-CoV-2 strains in NAbTs against B.1.351 and B.1.617.2 SARS-CoV-2 variants, including made via our electronic submission system at 106 participants (median age 34 years, after two doses of BNT162b2 B.1.617.2 (appendix p 3). This finding http://ees.elsevier.com/ IQR 29–42) after either one dose of (189 [97%] of 195 against B.1.351; and is in line with the vaccine-induced thelancet/ www.thelancet.com Published online June 28, 2021 https://doi.org/10.1016/S0140-6736(21)01462-8 1 Correspondence NAbTs observed during clinical trials of a more pronounced reduction in median Emma C Wall, Mary Wu, Ruth Harvey, AZD12224 and BNT162b2.7 Notably, NAbTs against B.1.617.2 between Gavin Kelly, Scott Warchal, our data are consistent with preliminary two-dose AZD1222 and two-dose Chelsea Sawyer, Rodney Daniels, observational estimates based on rates BNT162b2 recipients (appendix p 5). Lorin Adams, Philip Hobson, of S gene target failure during PCR Along with increased standardisation Emine Hatipoglu, Yenting Ngai, testing in England8 and more recent across serological laboratories, further Saira Hussain, Karen Ambrose, data from Scotland,9 which reports 19% serological examination of AZD1222 Steve Hindmarsh, Rupert Beale, reduced AZD1222 efficacy following two recipients will be needed as the UK Andrew Riddell, Steve Gamblin, doses (60%) relative to two doses of vaccination programme continues, to Michael Howell, George Kassiotis, BNT162b2 (79%) against the B.1.617.2 assess the extent to which variables such Vincenzo Libri, Bryan Williams, Charles Swanton, Sonia Gandhi, variant and similar to reduced efficacy as age affect NAbTs (especially beyond *David LV Bauer against the B.1.1.7 variant following the median 31 days post-second dose [email protected] two doses (73% for AZD1222 vs 92% for examined here) and vaccine efficacy, BNT162b2). The combination of these and to establish and refine correlates Francis Crick Institute, London NW1 1AT, UK (ECW, MW, RH, GKe, SW, CSa, RD, LA, PH, SHu, KA, SHi, observational data with our laboratory of protection against all SARS-CoV-2 RB, AR, SGam, MH, GKa, CSw, SGan, DLVB); data suggests that the correlation variants. National Institute for Health Research (NIHR) between NAbTs and vaccine efficacy in Our data reinforce the need to University College London Hospitals (UCLH) Biomedical Research Centre, London, UK (ECW, VL, 10 recent models continues to perform recognise the increased protection BW); NIHR UCLH Clinical Research Facility, London, well across different vaccine types and offered by a second vaccine dose UK (ECW, RB, VL, BW); University College London, SARS-CoV-2 variants (appendix p 5). It as COVID-19 cases associated with London, UK (RB, EH, YN, VL, BW, CSw, SGan); Department of Infectious Disease, St Mary’s further highlights that the lower starting the B.1.617.2 variant increase. They Hospital, Imperial College London, London, UK NAbTs of AZD1222 recipients will now also suggest that further booster (GKa) render vaccine efficacy more susceptible immunisations might be needed, 1 Public Health England. SARS-CoV-2 variants of to any possible individual-level variation especially for more susceptible groups concern and variants under investigation in England.
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