Efficacy of ChAdOx1 nCoV-19 (AZD1222) vaccine against SARS-CoV-2 variant of concern 202012/01 (B.1.1.7): an exploratory analysis of a randomised controlled trial

Abstract

Background A new variant of SARS-CoV-2, B.1.1.7, emerged as the dominant cause of COVID-19 disease in the UK from November, 2020. We report a post-hoc analysis of the efficacy of the adenoviral vector vaccine, ChAdOx1 nCoV-19 (AZD1222), against this variant. Methods Volunteers (aged ≥18 years) who were enrolled in phase 2/3 vaccine efficacy studies in the UK, and who were randomly assigned (1:1) to receive ChAdOx1 nCoV-19 or a meningococcal conjugate control (MenACWY) vaccine, provided upper airway swabs on a weekly basis and also if they developed symptoms of COVID-19 disease (a cough, a fever of 37·8°C or higher, shortness of breath, anosmia, or ageusia). Swabs were tested by nucleic acid amplification test (NAAT) for SARS-CoV-2 and positive samples were sequenced through the COVID-19 Genomics UK consortium. Neutralising antibody responses were measured using a live-virus microneutralisation assay against the B.1.1.7 lineage and a canonical non-B.1.1.7 lineage (Victoria). The efficacy analysis included symptomatic COVID-19 in seronegative participants with a NAAT positive swab more than 14 days after a second dose of vaccine. Participants were analysed according to vaccine received. Vaccine efficacy was calculated as 1 − relative risk (ChAdOx1 nCoV-19 vs MenACWY groups) derived from a robust Poisson regression model. This study is continuing and is registered with ClinicalTrials.gov , NCT04400838 , and ISRCTN, 15281137. Findings Participants in efficacy cohorts were recruited between May 31 and Nov 13, 2020, and received booster doses between Aug 3 and Dec 30, 2020. Of 8534 participants in the primary efficacy cohort, 6636 (78%) were aged 18–55 years and 5065 (59%) were female. Between Oct 1, 2020, and Jan 14, 2021, 520 participants developed SARS-CoV-2 infection. 1466 NAAT positive nose and throat swabs were collected from these participants during the trial. Of these, 401 swabs from 311 participants were successfully sequenced. Laboratory virus neutralisation activity by vaccine-induced antibodies was lower against the B.1.1.7 variant than against the Victoria lineage (geometric mean ratio 8·9, 95% CI 7·2–11·0). Clinical vaccine efficacy against symptomatic NAAT positive infection was 70·4% (95% CI 43·6–84·5) for B.1.1.7 and 81·5% (67·9–89·4) for non-B.1.1.7 lineages. Interpretation ChAdOx1 nCoV-19 showed reduced neutralisation activity against the B.1.1.7 variant compared with a non-B.1.1.7 variant in vitro, but the vaccine showed efficacy against the B.1.1.7 variant of SARS-CoV-2. Funding UK Research and Innovation, National Institute for Health Research (NIHR), Coalition for Epidemic Preparedness Innovations, NIHR Oxford Biomedical Research Centre, Thames Valley and South Midlands NIHR Clinical Research Network, and AstraZeneca.

SARS-CoV-2 variants, spike mutations and immune escape

“…Pseudoviruses carrying the set of B.1.1.7 spike mutations evaluated with postvaccination serum from individuals who received the BNT162b2 vaccine (two doses) 63 , 78 , 84 or mRNA-1273 vaccine (two doses) 63 exhibited only a modest reduction in neutralization titres (less than threefold). However, assays using pseudovirus carrying B.1.1.7 spike mutations and with the addition of E484K, a combination that has been observed in sequencing of circulating isolates, showed larger, more significant drops (6.7-fold) in neutralization with postvaccination sera isolated from individuals who received the BNT162b2 vaccine 85 . In a live-virus neutralization assay, neutralizing titres of ChAdOx1 nCoV-19 (Oxford–AstraZeneca) postvaccination sera were nine times lower than titres against the B.1.1.7 lineage relative to a canonical non-B.1.1.7 lineage (Wuhan-Hu-1 with the S247R spike mutation) 86 .…”

“…Early indications suggest that these are broadly consistent with the laboratory results, with the B.1.351 variant showing greater signs of vaccine escape. The ChAdOx1 nCoV-19 vaccine showed clinical efficacy against the B.1.1.7 variant but failed to provide protection against mild to moderate disease caused by the B.1.351 variant, with vaccine efficacy against the variant estimated at 10.4% (95% confidence interval −76.8 to 54.8) 85 , 86 , 91 . Preliminary data from clinical trials reported that the NVX-CoV2373 (Novavax) protein-based vaccine provides 95.6% efficacy against the wild-type virus and that this is moderately lower for the B.1.1.7 variant (85.6%) and is further reduced for the B.1.351 variant (60.0%) 91 .…”

Variant SARS-CoV-2 mRNA vaccines confer broad neutralization as primary or booster series in mice

“…26 Clinical studies in South Africa demonstrated reduced efficacy against symptomatic COVID-19 disease for the NVX-CoV2373 (Novavax), AZD1222 (University of Oxford/AstraZeneca), and Ad26.COV2.S (Janssen/Johnson & Johnson) vaccines. [27][28][29] Pfizer/BioNTech has recently issued a press release reporting high efficacy in a study with a small number of recipients of the mRNA BNT162b2 vaccine conducted in the same population; however, a report from Israel suggests increased breakthrough infection rates by B.1.351 in BNT162b2 vaccinated individuals. 30,31 Studies have demonstrated reduced neutralization titers against the full B.1.351 variant following mRNA-1273 vaccination, although levels are still significant and expected to be protective based on challenge studies in NHPs.…”

SARS-CoV-2 Portrayed Against HIV: Contrary Viral Strategies in Similar Disguise

“…Epidemiological studies suggest that the UK variant correlates with higher viral loads in patients [306], a >40% increased epidemiological growth [307,308], a longer duration of acute infection [309], and increased severity/death rate, particularly in patients of higher age and with comorbidities [310][311][312][313]. The UK variant acquired an enhanced affinity to ACE2 [314] while maintaining sensitivity to nAb responses though with 2-9 times reduced nAb titers in vaccinees and convalescent individuals [314][315][316]. Spike mutations present in the UK variant frequently confer resistance to NTD-directed nAbs, whereas neutralization by RBD-specific nAbs remains largely unaffected [317].…”