Background Cases of Middle East respiratory syndrome coronavirus (MERS-CoV) infection continue to rise in the Arabian Peninsula 7 years after it was first described in Saudi Arabia. MERS-CoV poses a significant risk to public health security because of an absence of currently available effective countermeasures. We aimed to assess the safety and immunogenicity of the candidate simian adenovirus-vectored vaccine expressing the full-length spike surface glycoprotein, ChAdOx1 MERS, in humans. MethodsThis dose-escalation, open-label, non-randomised, uncontrolled, phase 1 trial was done at the Centre for Clinical Vaccinology and Tropical Medicine (Oxford, UK) and included healthy people aged 18-50 years with negative pre-vaccination tests for HIV antibodies, hepatitis B surface antigen, and hepatitis C antibodies (and a negative urinary pregnancy test for women). Participants received a single intramuscular injection of ChAdOx1 MERS at three different doses: the low-dose group received 5 × 10⁹ viral particles, the intermediate-dose group received 2•5 × 10¹⁰ viral particles, and the high-dose group received 5 × 10¹⁰ viral particles. The primary objective was to assess safety and tolerability of ChAdOx1 MERS, measured by the occurrence of solicited, unsolicited, and serious adverse events after vaccination. The secondary objective was to assess the cellular and humoral immunogenicity of ChAdOx1 MERS, measured by interferon-γ-linked enzyme-linked immunospot, ELISA, and virus neutralising assays after vaccination. Participants were followed up for up to 12 months. This study is registered with ClinicalTrials.gov, NCT03399578. Findings Between March 14 and Aug 15, 2018, 24 participants were enrolled: six were assigned to the low-dose group, nine to the intermediate-dose group, and nine to the high-dose group. All participants were available for follow-up at 6 months, but five (one in the low-dose group, one in the intermediate-dose group, and three in the high-dose group) were lost to follow-up at 12 months. A single dose of ChAdOx1 MERS was safe at doses up to 5 × 10¹⁰ viral particles with no vaccine-related serious adverse events reported by 12 months. One serious adverse event reported was deemed to be not related to ChAdOx1 MERS. 92 (74% [95% CI 66-81]) of 124 solicited adverse events were mild, 31 (25% [18-33]) were moderate, and all were self-limiting. Unsolicited adverse events in the 28 days following vaccination considered to be possibly, probably, or definitely related to ChAdOx1 MERS were predominantly mild in nature and resolved within the follow-up period of 12 months. The proportion of moderate and severe adverse events was significantly higher in the high-dose group than in the intermediate-dose group (relative risk 5•83 [95% CI 2•11-17•42], p<0•0001) Laboratory adverse events considered to be at least possibly related to the study intervention were self-limiting and predominantly mild in severity. A significant increase from baseline in T-cell (p<0•003) and IgG (p<0•0001) responses to the MERS-CoV spike ant...

In order to understand the kinetics, timing and persistence of SARS-CoV2 neutralizing antibodies (Nabs) we used a surrogate viral neutralization test to evaluate their levels in patients with varying severity of illness, in those with prolonged shedding and those with mild/asymptomatic illness at various time points. Patients with severe or moderate COVID-19 illness had earlier appearance of Nabs at higher levels compared to those with mild or asymptomatic illness. Furthermore, those who had prolonged shedding of the virus, had Nabs appearing faster and at higher levels than those who cleared the virus earlier. Although all individuals appeared to be antibody positive by end of week 5, the positivity rates declined thereafter, especially in those who had mild or asymptomatic illness.

We discovered that values for 2 out of 79 antibodies have unfortunately been wrongly reported. For antibody FnC1t1p2_A5, the IC 100 is 50 mg/mL instead of 16 mg/mL; for antibody CnC2t1p1_B10, the IC 100 is >100 mg/mL instead of 12.5 mg/mL. For the latter antibody, binding characteristics were also corrected. As a consequence, the total number of neutralizing antibodies reported is 27 instead of 28. Changes affect Figures 3, 4, S3, S4, and S5, Tables S3 and S4, and text on pages 1, 3, 5, and 7. Importantly, the corrections have no impact on the conclusions in this paper. We apologize for any inconvenience that may have been caused by this error.

38The SARS-CoV-2 pandemic has unprecedented implications for public health, social 39 life, and world economy. Since approved drugs and vaccines are not available, new 40 options for COVID-19 treatment and prevention are highly demanded. To identify 41 SARS-CoV-2 neutralizing antibodies, we analysed the antibody response of 12 42 COVID-19 patients from 8 to 69 days post diagnosis. By screening 4,313 SARS-43CoV-2-reactive B cells, we isolated 255 antibodies from different time points as early 44 as 8 days post diagnosis. Among these, 28 potently neutralized authentic SARS-45CoV-2 (IC 100 as low as 0.04 µg/ml), showing a broad spectrum of V genes and low 46 levels of somatic mutations. Interestingly, potential precursors were identified in 47 naïve B cell repertoires from 48 healthy individuals that were sampled before the 48 COVID-19 pandemic. Our results demonstrate that SARS-CoV-2 neutralizing 49 antibodies are readily generated from a diverse pool of precursors, fostering the hope 50 of rapid induction of a protective immune response upon vaccination. 51 52