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.

BACKGROUND: A safe and efficacious vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), if deployed with high coverage, could contribute to the control of the COVID-19 pandemic. We evaluated the safety and efficacy of the ChAdOx1 nCoV-19 vaccine in a pooled interim analysis of four trials. METHODS: This analysis includes data from four ongoing blinded, randomised, controlled trials done across the UK, Brazil, and South Africa. Participants aged 18 years and older were randomly assigned (1:1) to ChAdOx1 nCoV-19 vaccine or control (meningococcal group A, C, W, and Y conjugate vaccine or saline). Participants in the ChAdOx1 nCoV-19 group received two doses containing 5 × 1010 viral particles (standard dose; SD/SD cohort); a subset in the UK trial received a half dose as their first dose (low dose) and a standard dose as their second dose (LD/SD cohort). The primary efficacy analysis included symptomatic COVID-19 in seronegative participants with a nucleic acid amplification test-positive swab more than 14 days after a second dose of vaccine. Participants were analysed according to treatment received, with data cutoff on Nov 4, 2020. Vaccine efficacy was calculated as 1 - relative risk derived from a robust Poisson regression model adjusted for age. Studies are registered at ISRCTN89951424 and ClinicalTrials.gov, NCT04324606, NCT04400838, and NCT04444674. FINDINGS: Between April 23 and Nov 4, 2020, 23 848 participants were enrolled and 11 636 participants (7548 in the UK, 4088 in Brazil) were included in the interim primary efficacy analysis. In participants who received two standard doses, vaccine efficacy was 62·1% (95% CI 41·0-75·7; 27 [0·6%] of 4440 in the ChAdOx1 nCoV-19 group vs71 [1·6%] of 4455 in the control group) and in participants who received a low dose followed by a standard dose, efficacy was 90·0% (67·4-97·0; three [0·2%] of 1367 vs 30 [2·2%] of 1374; pinteraction=0·010). Overall vaccine efficacy across both groups was 70·4% (95·8% CI 54·8-80·6; 30 [0·5%] of 5807 vs 101 [1·7%] of 5829). From 21 days after the first dose, there were ten cases hospitalised for COVID-19, all in the control arm; two were classified as severe COVID-19, including one death. There were 74 341 person-months of safety follow-up (median 3·4 months, IQR 1·3-4·8): 175 severe adverse events occurred in 168 participants, 84 events in the ChAdOx1 nCoV-19 group and 91 in the control group. Three events were classified as possibly related to a vaccine: one in the ChAdOx1 nCoV-19 group, one in the control group, and one in a participant who remains masked to group allocation. INTERPRETATION: ChAdOx1 nCoV-19 has an acceptable safety profile and has been found to be efficacious against symptomatic COVID-19 in this interim analysis of ongoing clinical trials. FUNDING: UK Research and Innovation, National Institutes for Health Research (NIHR), Coalition for Epidemic Preparedness Innovations, Bill & Melinda Gates Foundation, Lemann Foundation, Rede D'Or, Brava and Telles Foundation, NIHR Oxford Biomedical Research Centre, Thames Valley and South Midland's NIHR Clinical Research Network, and AstraZeneca

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

Background A safe and efficacious vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), if deployed with high coverage, could contribute to the control of the COVID-19 pandemic. We evaluated the safety and efficacy of the ChAdOx1 nCoV-19 vaccine in a pooled interim analysis of four trials. Methods This analysis includes data from four ongoing blinded, randomised, controlled trials done across the UK, Brazil, and South Africa. Participants aged 18 years and older were randomly assigned (1:1) to ChAdOx1 nCoV-19 vaccine or control (meningococcal group A, C, W, and Y conjugate vaccine or saline). Participants in the ChAdOx1 nCoV-19 group received two doses containing 5 × 1010 viral particles (standard dose; SD/SD cohort); a subset in the UK trial received a half dose as their first dose (low dose) and a standard dose as their second dose (LD/SD cohort). The primary efficacy analysis included symptomatic COVID-19 in seronegative participants with a nucleic acid amplification test-positive swab more than 14 days after a second dose of vaccine. Participants were analysed according to treatment received, with data cutoff on Nov 4, 2020. Vaccine efficacy was calculated as 1 - relative risk derived from a robust Poisson regression model adjusted for age. Studies are registered at ISRCTN89951424 and ClinicalTrials.gov, NCT04324606, NCT04400838, and NCT04444674. Findings Between April 23 and Nov 4, 2020, 23 848 participants were enrolled and 11 636 participants (7548 in the UK, 4088 in Brazil) were included in the interim primary efficacy analysis. In participants who received two standard doses, vaccine efficacy was 62·1% (95% CI 41·0–75·7; 27 [0·6%] of 4440 in the ChAdOx1 nCoV-19 group vs71 [1·6%] of 4455 in the control group) and in participants who received a low dose followed by a standard dose, efficacy was 90·0% (67·4–97·0; three [0·2%] of 1367 vs 30 [2·2%] of 1374; pinteraction=0·010). Overall vaccine efficacy across both groups was 70·4% (95·8% CI 54·8–80·6; 30 [0·5%] of 5807 vs 101 [1·7%] of 5829). From 21 days after the first dose, there were ten cases hospitalised for COVID-19, all in the control arm; two were classified as severe COVID-19, including one death. There were 74 341 person-months of safety follow-up (median 3·4 months, IQR 1·3–4·8): 175 severe adverse events occurred in 168 participants, 84 events in the ChAdOx1 nCoV-19 group and 91 in the control group. Three events were classified as possibly related to a vaccine: one in the ChAdOx1 nCoV-19 group, one in the control group, and one in a participant who remains masked to group allocation. Interpretation ChAdOx1 nCoV-19 has an acceptable safety profile and has been found to be efficacious against symptomatic COVID-19 in this interim analysis of ongoing clinical trials

Mathematical methods to quantify and characterise the primary elements of trophic systems

Mathematical approaches to plant characterisation are explained, there being a range of tools available to categorise and describe biological and environmental systems. Genetic algorithms (GAs) and fuzzy-logic are techniques used for multiple criteria-based decision-making. Data from a previously described algorithm are shown across an ecological continuum. Examples of the use of fuzzy logic to quantify environmental predictors are given. A fusion of techniques is proposed for the simultaneous categorisation of large numbers of plant species. The use of linguistic terms in fuzzy based systems is discussed and examples are given. Fuzzy systems use covariates of the prevailing conditions (water-energy dynamic) to guide characterisation of plants within different global environments. Knowledge guidance systems used with the technique for order similarity based on ideal situation (TOPSIS) categorise life history-based strategies of plants within trophic systems. Hybrid-techniques potential application to future research methods is given. © 2013 Inderscience Enterprises Ltd

Implementing stochastic distribution within the utopia plane of primary producers using a hybrid genetic algorithm

The two key variables in estimating the water-energy dynamic, which determines proportions of plant strategy components on a macro basis, are temperature and precipitation. Additionally, use of high-resolution elevation data facilitates formation of the fuzzy rule base for ordination of the strategical nodes. Application of adaptive neural fuzzy inference systems produces sets of rules, which may be minimised to increase the efficiency of modelling the distribution of plants and their characters. A modified objective genetic evolutionary algorithm was employed in this study to show the distribution of elements of strategies within a strength Pareto. Distribution of the elements showed an approximate Poisson curve in objective space that may be extrapolated to a real-numbered population via application of optimisation algorithms to reflect the stochastic organisation of the populations. © 2013 Inderscience Enterprises Ltd

Plant-parasitic nematodes parasitizing saffron in Morocco: Structuring drivers and biological risk identification

International audiencePlant-parasitic nematodes (PPN) are the most destructive of all plant pathogens. They are an economically important group of soil pathogens, causing significant annual damages of up to 25% of world crop production. Morocco is considered to be a highly productive country for the colorant/medicinal/spice saffron (Crocus sativus L.). Taliouine and Taznakht regions are the most productive areas of this valuable neutraceutical. Due to its metabolic profile, and growth forms, saffron is susceptible to many plant diseases, including plant-parasitic nematodes (PPN). This work aims to assess the diversity of PPN communities in soils of Taliouine and Taznakht regions to facilitate understanding of links between their assemblages with biotic and abiotic parameters. Herein, nematode communities were characterized in 163 soil samples collected from 11 rural communes characterized by altitudinal gradients in Taliouine and Taznakht regions. Fifteen PPN genera belonging to 12 families were identified, among which the four genera Ditylenchus, Aphelenchoides, Pratylenchus and Helicotylenchus, potentiate serious limiting factors in saffron production. Their frequencies are respectively 92, 49, 48 and 36% in the area of Taliouine, while in Taznakht they represent 95, 69, 33, and 28% respectively. Regarding the assessment of diversity at different sites, the genus richness (R) index ranges from 2 to 10 distinct genera, whereas the Shannon diversity (H’) index varies from 0.9 to 1.5 and the Evenness (E) index tends to 1. The Co-inertia analyses revealed a substantial relationship between nematode communities and soil types. Soil texture is the major factor influencing the presence and the abundance of a considerable portion of genera. Multivariate analyses (MBPLS) indicated links between humidity, rainfall, minimum temperature and PPN taxa, though maximum temperature did not have an impact. Ditylenchus, Helicotylenchus, Pratylenchus and Paratylenchus were related to the humidity and silt soil that developed in Taliouine. Aphelenchoides, Tylenchus, Tylenchorynchus and Dorylaimus were more prevalent in rainy locations and clay soils of Taznakht. Suitable nematode controlling approaches may be applied and preventative measures should be considered at nursery and field level

Terrestrial arthropods diversity in the Argan Biosphere Reserve: Seasonal dynamics and ecological function roles

Diversity, spatial patterns and temporal trends of terrestrial arthropod communities in the Arganeraie Biosphere Reserve of Morocco are poorly understood. Arthropods were seasonally sampled using pitfall traps at four sites, three of which are Argan forest ecosystem and one of which is a modern Argan grove. Diversity parameters were seasonally measured. Observation allowed identification of 161 morphospecies belonging to the five classes Chilopoda, Malacostraca, Collembola, Insecta and Arachnida were recorded. Captures were dominated by insects, representing more than 90% of the total trapped individuals. Insecta were the most diversified class (122 morphospecies), followed by Arachnida (33). The three other classes were less diversified with two species each. Among insects, Coleoptera and Hymenoptera were the most diversified groups. Diversity parameters exhibited seasonal variations. The highest arthropod abundance per sample was recorded during spring, while observed richness was higher in spring and summer. Shannon diversity index showed no significant difference among seasons. The composition of terrestrial arthropod communities between sites changed among seasons. A high dissimilarity was reported between the terrestrial arthropod community of Belfaa and those of other sites. The classification of arthropods into trophic guilds shows the importance of both predators and detritivores, which shows a higher abundance in spring and summer. Overall, predators guild richness was higher than others among seasons. This study highlights spatiotemporal diversity composition and structure of terrestrial arthropods community associated with the Argan ecosystem, complementing the unique diversity and proliferation of ecotypes present in Morocco

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.

BACKGROUND: The pandemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) might be curtailed by vaccination. We assessed the safety, reactogenicity, and immunogenicity of a viral vectored coronavirus vaccine that expresses the spike protein of SARS-CoV-2. METHODS: We did a phase 1/2, single-blind, randomised controlled trial in five trial sites in the UK of a chimpanzee adenovirus-vectored vaccine (ChAdOx1 nCoV-19) expressing the SARS-CoV-2 spike protein compared with a meningococcal conjugate vaccine (MenACWY) as control. Healthy adults aged 18-55 years with no history of laboratory confirmed SARS-CoV-2 infection or of COVID-19-like symptoms were randomly assigned (1:1) to receive ChAdOx1 nCoV-19 at a dose of 5 × 1010 viral particles or MenACWY as a single intramuscular injection. A protocol amendment in two of the five sites allowed prophylactic paracetamol to be administered before vaccination. Ten participants assigned to a non-randomised, unblinded ChAdOx1 nCoV-19 prime-boost group received a two-dose schedule, with the booster vaccine administered 28 days after the first dose. Humoral responses at baseline and following vaccination were assessed using a standardised total IgG ELISA against trimeric SARS-CoV-2 spike protein, a muliplexed immunoassay, three live SARS-CoV-2 neutralisation assays (a 50% plaque reduction neutralisation assay [PRNT50]; a microneutralisation assay [MNA50, MNA80, and MNA90]; and Marburg VN), and a pseudovirus neutralisation assay. Cellular responses were assessed using an ex-vivo interferon-γ enzyme-linked immunospot assay. The co-primary outcomes are to assess efficacy, as measured by cases of symptomatic virologically confirmed COVID-19, and safety, as measured by the occurrence of serious adverse events. Analyses were done by group allocation in participants who received the vaccine. Safety was assessed over 28 days after vaccination. Here, we report the preliminary findings on safety, reactogenicity, and cellular and humoral immune responses. The study is ongoing, and was registered at ISRCTN, 15281137, and ClinicalTrials.gov, NCT04324606. FINDINGS: Between April 23 and May 21, 2020, 1077 participants were enrolled and assigned to receive either ChAdOx1 nCoV-19 (n=543) or MenACWY (n=534), ten of whom were enrolled in the non-randomised ChAdOx1 nCoV-19 prime-boost group. Local and systemic reactions were more common in the ChAdOx1 nCoV-19 group and many were reduced by use of prophylactic paracetamol, including pain, feeling feverish, chills, muscle ache, headache, and malaise (all p<0·05). There were no serious adverse events related to ChAdOx1 nCoV-19. In the ChAdOx1 nCoV-19 group, spike-specific T-cell responses peaked on day 14 (median 856 spot-forming cells per million peripheral blood mononuclear cells, IQR 493-1802; n=43). Anti-spike IgG responses rose by day 28 (median 157 ELISA units [EU], 96-317; n=127), and were boosted following a second dose (639 EU, 360-792; n=10). Neutralising antibody responses against SARS-CoV-2 were detected in 32 (91%) of 35 participants after a single dose when measured in MNA80 and in 35 (100%) participants when measured in PRNT50. After a booster dose, all participants had neutralising activity (nine of nine in MNA80 at day 42 and ten of ten in Marburg VN on day 56). Neutralising antibody responses correlated strongly with antibody levels measured by ELISA (R2=0·67 by Marburg VN; p<0·001). INTERPRETATION: ChAdOx1 nCoV-19 showed an acceptable safety profile, and homologous boosting increased antibody responses. These results, together with the induction of both humoral and cellular immune responses, support large-scale evaluation of this candidate vaccine in an ongoing phase 3 programme. FUNDING: UK Research and Innovation, Coalition for Epidemic Preparedness Innovations, National Institute for Health Research (NIHR), NIHR Oxford Biomedical Research Centre, Thames Valley and South Midland's NIHR Clinical Research Network, and the German Center for Infection Research (DZIF), Partner site Gießen-Marburg-Langen