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

Biofortification of wheat, rice and common bean by applying foliar zinc fertilizer along with pesticides in seven countries

Rice (Oryza sativa L.), wheat (Triticum aestivum L.) and common bean (Phaseolus vulgaris L.) are major staple food crops consumed worldwide. Zinc (Zn) deficiency represents a common micronutrient deficiency in human populations, especially in regions of the world where staple food crops are the main source of daily calorie intake. Foliar application of Zn fertilizer has been shown to be effective for enriching food crop grains with Zn to desirable amounts for human nutrition. For promoting adoption of this practice by growers, it is important to know whether foliar Zn fertilizers can be applied along with pesticides to wheat, rice and also common bean grown across different soil and environmental conditions. The feasibility of foliar application of zinc sulphate (ZnSO4.7H(2)O) to wheat, rice and common bean in combination with commonly used five fungicides and nine insecticides was investigated under field conditions at the 31 sites-years of seven countries, i.e., China, India, Pakistan, Thailand, Turkey, Brazil and Zambia. Significant increases in grain yields were observed with foliar Zn/foliar Zn + pesticide (5.2-7.7 % of wheat and 1.6-4.2 % of rice) over yields with no Zn treatment. In wheat, as average of all experiments, higher grain Zn concentrations were recorded with foliar Zn alone (41.2 mg kg(-1)) and foliar Zn + pesticide (38.4 mg kg(-1)) as compared to no Zn treatment (28.0 mg kg(-1)). Though the magnitude of grain Zn enrichment was lesser in rice than wheat, grain Zn concentrations in brown rice were significantly higher with foliar Zn (24.1 mg kg(-1)) and foliar Zn + pesticide (23.6 mg kg(-1)) than with no Zn (19.1 mg kg(-1)). In case of common bean, grain Zn concentration increased from 68 to 78 mg kg(-1) with foliar Zn alone and to 77 mg kg(-1) with foliar Zn applied in combination with pesticides. Thus, grain Zn enrichment with foliar Zn, without or with pesticides, was almost similar in all the tested crops. The results obtained at the 31 experimental site-years of seven countries revealed that foliar Zn fertilization can be realized in combination with commonly-applied pesticides to contribute Zn biofortification of grains in wheat, rice and common bean. This agronomic approach represents a useful practice for the farmers to alleviate Zn deficiency problem in human populations