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•COVID-19 vaccine efficacy (VE) varies against SARS-CoV-2 variants of concern.•We present a final VE analysis from a phase 1b/2 AZD1222 trial in South Africa.•VE was 90% for WT, 6.7% for Beta and 77.1% for Delta ≥ 9 months post-vaccination.•Safety was consistent with the interim analysis and no new concerns were reported.•AZD1222 offers durable protection, potentially due to anamnestic immune responses. COVID-19 vaccine efficacy (VE) has been observed to vary against antigenically distinct SARS-CoV-2 variants of concern (VoC). Here we report the final analysis of VE and safety from COV005: a phase 1b/2, multicenter, double-blind, randomized, placebo-controlled study of primary series AZD1222 (ChAdOx1 nCoV-19) vaccination in South African adults aged 18–65 years. South Africa’s first, second, and third waves of SARS-CoV-2 infections were respectively driven by the ancestral SARS-CoV-2 virus (wild type, WT), and SARS-CoV-2 Beta and Delta VoCs. VE against asymptomatic and symptomatic infection was 90.6% for WT, 6.7% for Beta and 77.1% for Delta. No cases of severe COVID-19 were documented ahead of unblinding. Safety was consistent with the interim analysis, with no new safety concerns identified. Notably, South Africa’s Delta wave occurred ≥ 9 months after primary series vaccination, suggesting that primary series AZD1222 vaccination offers a good durability of protection, potentially due to an anamnestic response. Clinical trial identifier: CT.gov NCT04444674.

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. 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. 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. 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. 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.

We evaluated EP HIV-1090 vaccine, a DNA plasmid encoding 21 cytotoxic T-lymphocyte (CTL) epitopes of human immunodeficiency virus type 1 (HIV-1) and the pan-DR helper T-lymphocyte epitope (PADRE), in a dose escalation, randomized, double-blinded, placebo-controlled Phase 1 trial. Vaccine, at 0.5, 2.0, or 4.0 mg doses, or placebo was injected four times over 6 months. Forty-two healthy, HIV-1-uninfected adults were enrolled. Using an interferon-γ ELISPOT assay, a response to PADRE was detected in one vaccine recipient. Three vaccine recipients raised anti-HIV-1 CD8+ CTL measured by chromium-release assay. The vaccine was safe and well-tolerated, but only weakly immunogenic.

Background RSV is the principal cause of lower respiratory tract infection (LRTI) among infants, and a significant unmet need exists for RSV prevention in healthy infants. We have developed a highly potent, extended half-life monoclonal antibody (mAb), to protect infants for an entire RSV season using a single IM dose. Here we report the efficacy, safety, pharmacokinetics, and anti-drug antibody (ADA) responses for MEDI8897 in palivizumab-ineligible preterm infants born between 29 and 35 weeks gestation. Methods A total of 1,453 Infants were randomized 2:1 to receive a single 50 mg IM injection of MEDI8897 (n = 969) or placebo (n = 484) and followed for 360 days. Enrollment occurred just prior to the 2016 and 2017 RSV seasons in 23 northern and southern hemisphere countries. Blood was collected periodically. Infants with a medically attended (MA) LRTI (outpatient or inpatient) had nasal swabs obtained for central RSV testing by RT-PCR. Predefined clinical criteria were used for the case definition. Results A total of 1,417 (97.5%) subjects completed the 150-day efficacy follow-up period and 1,367 (94.1%) completed the study. In the MEDI8897 group, a 70.1% (95% CI: 52.3%, 81.2%; P < 0.0001) reduction in the incidence of medically attended RSV LRTI and a 78.4% (95% CI: 51.9%, 90.3%; P = 0.0002) reduction in the incidence of RSV LRTI hospitalization was achieved. These efficacy results were consistent when analyzed by hemisphere, RSV subtype, and subject demographics. Similar proportions of adverse events (86.8% placebo; 86.2% MEDI8897) and serious adverse events (16.9% placebo; 11.2% MEDI8897) were reported in study subjects. There were no significant hypersensitivity reactions with similar proportions reported for both groups (0.6% placebo; 0.5% MEDI8897). The incidence of ADA detected any time post baseline was low (3.8% placebo; 5.6% MEDI8897) with no impact on PK or safety. The occurrence of non-RSV LRTIs was similar for both groups indicating no replacement by other pathogens. Conclusion In this large randomized study of RSV prophylaxis in healthy preterm infants, MEDI8897 immunoprophylaxis provided a significant reduction in RSV MA-LRTI and hospitalization. These results have promising implications for the future of RSV prophylaxis for all infants. This study was funded by AstraZeneca and sanofi pasteur. Disclosures All Authors: No reported Disclosures.