Safety and immunogenicity of the SARS-CoV-2 ARCoV mRNA vaccine in Chinese adults: a randomised, double-blind, placebo-controlled, phase 1 trial.

Safe and effective vaccines are urgently needed to end the COVID-19 pandemic caused by SARS-CoV-2 infection. We aimed to assess the preliminary safety, tolerability, and immunogenicity of an mRNA vaccine ARCoV, which encodes the SARS-CoV-2 spike protein receptor-binding domain (RBD). This single centre, double-blind, randomised, placebo-controlled, dose-escalation, phase 1 trial of ARCoV was conducted at Shulan (Hangzhou) hospital in Hangzhou, Zhejiang province, China. Healthy adults aged 18-59 years negative for SARS-CoV-2 infection were enrolled and randomly assigned using block randomisation to receive an intramuscular injection of vaccine or placebo. Vaccine doses were 5 μg, 10 μg, 15 μg, 20 μg, and 25 μg. The first six participants in each block were sentinels and along with the remaining 18 participants, were randomly assigned to groups (5:1). In block 1 sentinels were given the lowest vaccine dose and after a 4-day observation with confirmed safety analyses, the remaining 18 participants in the same dose group proceeded and sentinels in block 2 were given their first administration on a two-dose schedule, 28 days apart. All participants, investigators, and staff doing laboratory analyses were masked to treatment allocation. Humoral responses were assessed by measuring anti-SARS-CoV-2 RBD IgG using a standardised ELISA and neutralising antibodies using pseudovirus-based and live SARS-CoV-2 neutralisation assays. SARS-CoV-2 RBD-specific T-cell responses, including IFN-γ and IL-2 production, were assessed using an enzyme-linked immunospot (ELISpot) assay. The primary outcome for safety was incidence of adverse events or adverse reactions within 60 min, and at days 7, 14, and 28 after each vaccine dose. The secondary safety outcome was abnormal changes detected by laboratory tests at days 1, 4, 7, and 28 after each vaccine dose. For immunogenicity, the secondary outcome was humoral immune responses: titres of neutralising antibodies to live SARS-CoV-2, neutralising antibodies to pseudovirus, and RBD-specific IgG at baseline and 28 days after first vaccination and at days 7, 15, and 28 after second vaccination. The exploratory outcome was SARS-CoV-2-specific T-cell responses at 7 days after the first vaccination and at days 7 and 15 after the second vaccination. This trial is registered with www.chictr.org.cn (ChiCTR2000039212). Between Oct 30 and Dec 2, 2020, 230 individuals were screened and 120 eligible participants were randomly assigned to receive five-dose levels of ARCoV or a placebo (20 per group). All participants received the first vaccination and 118 received the second dose. No serious adverse events were reported within 56 days after vaccination and the majority of adverse events were mild or moderate. Fever was the most common systemic adverse reaction (one [5%] of 20 in the 5 μg group, 13 [65%] of 20 in the 10 μg group, 17 [85%] of 20 in the 15 μg group, 19 [95%] of 20 in the 20 μg group, 16 [100%] of 16 in the 25 μg group; p<0·0001). The incidence of grade 3 systemic adverse events were none (0%) of 20 in the 5 μg group, three (15%) of 20 in the 10 μg group, six (30%) of 20 in the 15 μg group, seven (35%) of 20 in the 20 μg group, five (31%) of 16 in the 25 μg group, and none (0%) of 20 in the placebo group (p=0·0013). As expected, the majority of fever resolved in the first 2 days after vaccination for all groups. The incidence of solicited systemic adverse events was similar after administration of ARCoV as a first or second vaccination. Humoral immune responses including anti-RBD IgG and neutralising antibodies increased significantly 7 days after the second dose and peaked between 14 and 28 days thereafter. Specific T-cell response peaked between 7 and 14 days after full vaccination. 15 μg induced the highest titre of neutralising antibodies, which was about twofold more than the antibody titre of convalescent patients with COVID-19. ARCoV was safe and well tolerated at all five doses. The acceptable safety profile, together with the induction of strong humoral and cellular immune responses, support further clinical testing of ARCoV at a large scale. National Key Research and Development Project of China, Academy of Medical Sciences China, National Natural Science Foundation China, and Chinese Academy of Medical Sciences.

Chen GL ，Li XF ，Dai XH ，Li N ，Cheng ML ，Huang Z ，Shen J ，Ge YH ，Shen ZW ，Deng YQ ，Yang SY ，Zhao H ，Zhang NN ，Zhang YF ，Wei L ，Wu KQ ，Zhu MF ，Peng CG ，Jiang Q ，Cao SC ，Li YH ，Zhao DH ，Wu XH ，Ni L ，Shen HH ，Dong C ，Ying B ，Sheng GP ，Qin CF ，Gao HN ，Li LJ ... -  《Lancet Microbe》

Safety and immunogenicity of a recombinant tandem-repeat dimeric RBD-based protein subunit vaccine (ZF2001) against COVID-19 in adults: two randomised, double-blind, placebo-controlled, phase 1 and 2 trials.

Although several COVID-19 vaccines have been developed so far, they will not be sufficient to meet the global demand. Development of a wider range of vaccines, with different mechanisms of action, could help control the spread of SARS-CoV-2 globally. We developed a protein subunit vaccine against COVID-19 using a dimeric form of the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein as the antigen. We aimed to assess the safety and immunogenicity of this vaccine, ZF2001, and determine the appropriate dose and schedule for an efficacy study. We did two randomised, double-blind, placebo-controlled, phase 1 and phase 2 trials. Phase 1 was done at two university hospitals in Chongqing and Beijing, China, and phase 2 was done at the Hunan Provincial Center for Disease Control and Prevention in Xiangtan, China. Healthy adults aged 18-59 years, without a history of SARS-CoV or SARS-CoV-2 infection, an RT-PCR-positive test result for SARS-CoV-2, a history of contact with confirmed or suspected COVID-19 cases, and severe allergies to any component of the vaccine were eligible for enrolment. In phase 1, participants were randomly assigned (2:2:1) to receive three doses of the vaccine (25 μg or 50 μg) or placebo intramuscularly, 30 days apart. In phase 2, participants were randomly assigned (1:1:1:1:1:1) to receive the vaccine (25 μg or 50 μg) or placebo intramuscularly, 30 days apart, in either a two-dose schedule or a three-dose schedule. Investigators, participants, and the laboratory team were masked to group allocation. For phase 1, the primary outcome was safety, measured by the occurrence of adverse events and serious adverse events. For phase 2, the primary outcome was safety and immunogenicity (the seroconversion rate and the magnitude, in geometric mean titres [GMTs], of SARS-CoV-2-neutralising antibodies). Analyses were done on an intention-to-treat and per-protocol basis. These trials are registered with ClinicalTrials.gov (NCT04445194 and NCT04466085) and participant follow-up is ongoing. Between June 22 and July 3, 2020, 50 participants were enrolled into the phase 1 trial and randomly assigned to receive three doses of placebo (n=10), the 25 μg vaccine (n=20), or the 50 μg vaccine (n=20). The mean age of participants was 32·6 (SD 9·4) years. Between July 12 and July 17, 2020, 900 participants were enrolled into the phase 2 trial and randomly assigned to receive two doses of placebo (n=150), 25 μg vaccine (n=150), or 50 μg vaccine (n=150), or three doses of placebo (n=150), 25 μg vaccine (n=150), or 50 μg vaccine (n=150). The mean age of participants was 43·5 (SD 9·2) years. In both phase 1 and phase 2, adverse events reported within 30 days after vaccination were mild or moderate (grade 1 or 2) in most cases (phase 1: six [60%] of ten participants in the placebo group, 14 [70%] of 20 in the 25 μg group, and 18 [90%] of 20 in the 50 μg group; phase 2: 37 [25%] of 150 in the two-dose placebo group, 43 [29%] of 150 in the two-dose 25 μg group, 50 [33%] of 150 in the two-dose 50 μg group, 47 [31%] of 150 in the three-dose placebo group, 72 [48%] of 150 in the three-dose 25 μg group, and 65 [43%] of 150 in the three-dose 50 μg group). In phase 1, two (10%) grade 3 or worse adverse events were reported in the 50 μg group. In phase 2, grade 3 or worse adverse events were reported by 18 participants (four [3%] in the two-dose 25 μg vaccine group, two [1%] in the two-dose 50 μg vaccine group, two [1%] in the three-dose placebo group, four [3%] in the three-dose 25 μg vaccine group, and six [4%] in the three-dose 50 μg vaccine group), and 11 were considered vaccine related (two [1%] in the two-dose 25 μg vaccine group, one [1%] in the two-dose 50 μg vaccine group, one [1%] in the three-dose placebo group, two [1%] in the three-dose 25 μg vaccine group, and five [3%] in the three-dose 50 μg vaccine group); seven participants reported serious adverse events (one [1%] in the two-dose 25 μg vaccine group, one [1%] in the two-dose 50 μg vaccine group, two [1%] in the three-dose placebo group, one [1%] in the three-dose 25 μg vaccine group, and two [1%] in the three-dose 50 μg vaccine group), but none was considered vaccine related. In phase 2, on the two-dose schedule, seroconversion rates of neutralising antibodies 14 days after the second dose were 76% (114 of 150 participants) in the 25 μg group and 72% (108 of 150) in the 50 μg group; on the three-dose schedule, seroconversion rates of neutralising antibodies 14 days after the third dose were 97% (143 of 148 participants) in the 25 μg group and 93% (138 of 148) in the 50 μg group. In the two-dose groups in phase 2, the SARS-CoV-2-neutralising GMTs 14 days after the second dose were 17·7 (95% CI 13·6-23·1) in the 25 μg group and 14·1 (10·8-18·3) in the 50 μg group. In the three-dose groups in phase 2, the SARS-CoV-2-neutralising GMTs 14 days after the third dose were 102·5 (95% CI 81·8-128·5) in the 25 μg group and 69·1 (53·0-90·0) in the 50 μg group. The protein subunit vaccine ZF2001 appears to be well tolerated and immunogenic. The safety and immunogenicity data from the phase 1 and 2 trials support the use of the 25 μg dose in a three-dose schedule in an ongoing phase 3 trial for large-scale evaluation of ZF2001's safety and efficacy. National Program on Key Research Project of China, National Science and Technology Major Projects of Drug Discovery, Strategic Priority Research Program of the Chinese Academy of Sciences, and Anhui Zhifei Longcom Biopharmaceutical. For the Chinese translation of the abstract see Supplementary Materials section.

Yang S ，Li Y ，Dai L ，Wang J ，He P ，Li C ，Fang X ，Wang C ，Zhao X ，Huang E ，Wu C ，Zhong Z ，Wang F ，Duan X ，Tian S ，Wu L ，Liu Y ，Luo Y ，Chen Z ，Li F ，Li J ，Yu X ，Ren H ，Liu L ，Meng S ，Yan J ，Hu Z ，Gao L ，Gao GF ... -  《-》

Safety and immunogenicity of a protein subunit COVID-19 vaccine (ZF2001) in healthy children and adolescents aged 3-17 years in China: a randomised, double-blind, placebo-controlled, phase 1 trial and an open-label, non-randomised, non-inferiority, phase

ZF2001 is a recombinant protein subunit vaccine against SARS-CoV-2 that has been approved for use in China, Colombia, Indonesia, and Uzbekistan in adults aged 18 years or older, but not yet in children and adolescents younger than 18 years. We aimed to evaluate the safety and immunogenicity of ZF2001 in children and adolescents aged 3-17 years in China. The randomised, double-blind, placebo-controlled, phase 1 trial and the open-label, non-randomised, non-inferiority, phase 2 trial were done at the Xiangtan Center for Disease Control and Prevention (Hunan Province, China). Healthy children and adolescents aged 3-17 years, without a history of SARS-CoV-2 vaccination, without a history of COVID-19, without COVID-19 at the time of the study, and without contact with patients with confirmed or suspected COVID-19 were included in the phase 1 and phase 2 trials. In the phase 1 trial, participants were divided into three groups according to age (3-5 years, 6-11 years, and 12-17 years). Each group was randomly assigned (4:1), using block randomisation with five blocks, each with a block size of five, to receive three 25 μg doses of the vaccine, ZF2001, or placebo intramuscularly in the arm 30 days apart. The participants and investigators were masked to treatment allocation. In the phase 2 trial, participants received three 25 μg doses of ZF2001 30 days apart and remained stratified by age group. For phase 1, the primary endpoint was safety and the secondary endpoint was immunogenicity (humoral immune response on day 30 after the third vaccine dose: geometric mean titre [GMT] of prototype SARS-CoV-2 neutralising antibodies and seroconversion rate, and geometric mean concentration [GMC] of prototype SARS-CoV-2 receptor-binding domain [RBD]-binding IgG antibodies and seroconversion rate). For phase 2, the primary endpoint was the GMT of SARS-CoV-2 neutralising antibodies with seroconversion rate on day 14 after the third vaccine dose, and the secondary endpoints included the GMT of RBD-binding antibodies and seroconversion rate on day 14 after the third vaccine dose, the GMT of neutralising antibodies against the omicron BA.2 subvariant and seroconversion rate on day 14 after the third vaccine dose, and safety. Safety was analysed in participants who received at least one dose of the vaccine or placebo. Immunogenicity was analysed in the full-analysis set (ie, participants who received at least one dose and had antibody results) by intention to treat and in the per-protocol set (ie, participants who completed the whole vaccination course and had antibody results). Non-inferiority in the phase 2 trial (neutralising antibody titre of participants from this trial aged 3-17 years vs that of participants aged 18-59 years from a separate phase 3 trial) for clinical outcome assessment was based on the geometric mean ratio (GMR) and was considered met if the lower bound of the 95% CI for the GMR was 0·67 or greater. These trials are registered with ClinicalTrials.gov, NCT04961359 (phase 1) and NCT05109598 (phase 2). Between July 10 and Sept 4, 2021, 75 children and adolescents were randomly assigned to receive ZF2001 (n=60) or placebo (n=15) in the phase 1 trial and were included in safety and immunogenicity analyses. Between Nov 5, 2021, and Feb 14, 2022, 400 participants (130 aged 3-7 years, 210 aged 6-11 years, and 60 aged 12-17 years) were included in the phase 2 trial and were included in the safety analysis; six participants were excluded from the immunogenicity analyses. 25 (42%) of 60 participants in the ZF2001 group and seven (47%) of 15 participants in the placebo group in phase 1, and 179 (45%) of 400 participants in phase 2, had adverse events within 30 days after the third vaccination, without a significant difference between groups in phase 1. Most adverse events were grade 1 or 2 (73 [97%] of 75 in the phase 1 trial, and 391 [98%] of 400 in the phase 2 trial). One participant in the phase 1 trial and three in the phase 2 trial who received ZF2001 had serious adverse events. One serious adverse event (acute allergic dermatitis) in the phase 2 trial was possibly related to the vaccine. In the phase 1 trial, on day 30 after the third dose, in the ZF2001 group, seroconversion of neutralising antibodies against SARS-CoV-2 was observed in 56 (93%; 95% CI 84-98) of 60 participants, with a GMT of 176·5 (95% CI 118·6-262·8), and seroconversion of RBD-binding antibodies was observed in all 60 (100%; 95% CI 94-100) participants, with a GMC of 47·7 IU/mL (95% CI 40·1-56·6). In the phase 2 trial, on day 14 after the third dose, seroconversion of neutralising antibodies against SARS-CoV-2 was seen in 392 (99%; 95% CI 98-100) participants, with a GMT of 245·4 (95% CI 220·0-273·7), and seroconversion of RBD-binding antibodies was observed in all 394 (100%; 99-100) participants, with a GMT of 8021 (7366-8734). On day 14 after the third dose, seroconversion of neutralising antibodies against the omicron subvariant BA.2 was observed in 375 (95%; 95% CI 93-97) of 394 participants, with a GMT of 42·9 (95% CI 37·9-48·5). For the non-inferiority comparison of participants aged 3-17 years with those aged 18-59 years for SARS-CoV-2 neutralising antibodies, the adjusted GMR was 8·6 (95% CI 7·0-10·4), with the lower bound of the GMR greater than 0·67. ZF2001 is safe, well tolerated, and immunogenic in children and adolescents aged 3-17 years. Vaccine-elicited sera can neutralise the omicron BA.2 subvariant, but with reduced activity. The results support further studies of ZF2001 in children and adolescents. Anhui Zhifei Longcom Biopharmaceutical and the Excellent Young Scientist Program from National Natural Science Foundation of China. For the Chinese translation of the abstract see Supplementary Materials section.

Gao L ，Li Y ，He P ，Chen Z ，Yang H ，Li F ，Zhang S ，Wang D ，Wang G ，Yang S ，Gong L ，Ding F ，Ling M ，Wang X ，Ci L ，Dai L ，Gao GF ，Huang T ，Hu Z ，Ying Z ，Sun J ，Zuo X ... -  《-》

Safety, tolerability, and immunogenicity of an inactivated SARS-CoV-2 vaccine in healthy adults aged 18-59 years: a randomised, double-blind, placebo-controlled, phase 1/2 clinical trial.

With the unprecedented morbidity and mortality associated with the COVID-19 pandemic, a vaccine against COVID-19 is urgently needed. We investigated CoronaVac (Sinovac Life Sciences, Beijing, China), an inactivated vaccine candidate against COVID-19, containing inactivated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), for its safety, tolerability and immunogenicity. In this randomised, double-blind, placebo-controlled, phase 1/2 clinical trial, healthy adults aged 18-59 years were recruited from the community in Suining County of Jiangsu province, China. Adults with SARS-CoV-2 exposure or infection history, with axillary temperature above 37·0°C, or an allergic reaction to any vaccine component were excluded. The experimental vaccine for the phase 1 trial was manufactured using a cell factory process (CellSTACK Cell Culture Chamber 10, Corning, Wujiang, China), whereas those for the phase 2 trial were produced through a bioreactor process (ReadyToProcess WAVE 25, GE, Umea, Sweden). The phase 1 trial was done in a dose-escalating manner. At screening, participants were initially separated (1:1), with no specific randomisation, into two vaccination schedule cohorts, the days 0 and 14 vaccination cohort and the days 0 and 28 vaccination cohort, and within each cohort the first 36 participants were assigned to block 1 (low dose CoronaVac [3 μg per 0·5 mL of aluminium hydroxide diluent per dose) then another 36 were assigned to block 2 (high-dose Coronavc [6 μg per 0·5 mL of aluminium hydroxide diluent per dse]). Within each block, participants were randomly assigned (2:1), using block randomisation with a block size of six, to either two doses of CoronaVac or two doses of placebo. In the phase 2 trial, at screening, participants were initially separated (1:1), with no specific randomisation, into the days 0 and 14 vaccination cohort and the days 0 and 28 vaccination cohort, and participants were randomly assigned (2:2:1), using block randomisation with a block size of five, to receive two doses of either low-dose CoronaVac, high-dose CoronaVac, or placebo. Participants, investigators, and laboratory staff were masked to treatment allocation. The primary safety endpoint was adverse reactions within 28 days after injection in all participants who were given at least one dose of study drug (safety population). The primary immunogenic outcome was seroconversion rates of neutralising antibodies to live SARS-CoV-2 at day 14 after the last dose in the days 0 and 14 cohort, and at day 28 after the last dose in the days 0 and 28 cohort in participants who completed their allocated two-dose vaccination schedule (per-protocol population). This trial is registered with ClinicalTrials.gov, NCT04352608, and is closed to accrual. Between April 16 and April 25, 2020, 144 participants were enrolled in the phase 1 trial, and between May 3 and May 5, 2020, 600 participants were enrolled in the phase 2 trial. 743 participants received at least one dose of investigational product (n=143 for phase 1 and n=600 for phase 2; safety population). In the phase 1 trial, the incidence of adverse reactions for the days 0 and 14 cohort was seven (29%) of 24 participants in the 3 ug group, nine (38%) of 24 in the 6 μg group, and two (8%) of 24 in the placebo group, and for the days 0 and 28 cohort was three (13%) of 24 in the 3 μg group, four (17%) of 24 in the 6 μg group, and three (13%) of 23 in the placebo group. The seroconversion of neutralising antibodies on day 14 after the days 0 and 14 vaccination schedule was seen in 11 (46%) of 24 participants in the 3 μg group, 12 (50%) of 24 in the 6 μg group, and none (0%) of 24 in the placebo group; whereas at day 28 after the days 0 and 28 vaccination schedule, seroconversion was seen in 20 (83%) of 24 in the 3 μg group, 19 (79%) of 24 in the 6 μg group, and one (4%) of 24 in the placebo group. In the phase 2 trial, the incidence of adverse reactions for the days 0 and 14 cohort was 40 (33%) of 120 participants in the 3 μg group, 42 (35%) of 120 in the 6 μg group, and 13 (22%) of 60 in the placebo group, and for the days 0 and 28 cohort was 23 (19%) of 120 in the 3 μg group, 23 (19%) of 120 in the 6 μg group, and 11 (18%) of 60 for the placebo group. Seroconversion of neutralising antibodies was seen for 109 (92%) of 118 participants in the 3 μg group, 117 (98%) of 119 in the 6 μg group, and two (3%) of 60 in the placebo group at day 14 after the days 0 and 14 schedule; whereas at day 28 after the days 0 and 28 schedule, seroconversion was seen in 114 (97%) of 117 in the 3 μg group, 118 (100%) of 118 in the 6 μg group, and none (0%) of 59 in the placebo group. Taking safety, immunogenicity, and production capacity into account, the 3 μg dose of CoronaVac is the suggested dose for efficacy assessment in future phase 3 trials. Chinese National Key Research and Development Program and Beijing Science and Technology Program.

Zhang Y ，Zeng G ，Pan H ，Li C ，Hu Y ，Chu K ，Han W ，Chen Z ，Tang R ，Yin W ，Chen X ，Hu Y ，Liu X ，Jiang C ，Li J ，Yang M ，Song Y ，Wang X ，Gao Q ，Zhu F ... -  《-》

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.

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. 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. 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). 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. 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.

Folegatti PM ，Ewer KJ ，Aley PK ，Angus B ，Becker S ，Belij-Rammerstorfer S ，Bellamy D ，Bibi S ，Bittaye M ，Clutterbuck EA ，Dold C ，Faust SN ，Finn A ，Flaxman AL ，Hallis B ，Heath P ，Jenkin D ，Lazarus R ，Makinson R ，Minassian AM ，Pollock KM ，Ramasamy M ，Robinson H ，Snape M ，Tarrant R ，Voysey M ，Green C ，Douglas AD ，Hill AVS ，Lambe T ，Gilbert SC ，Pollard AJ ，Oxford COVID Vaccine Trial Group ... -  《-》