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BackgroundVaccine nationalism has become a key topic of discussion during the development, testing, and rollout of COVID-19 vaccines. Media attention has highlighted the ways that global, coordinated access to vaccines has been limited during the pandemic. It has also exposed how some countries have secured vaccine supply, through bilateral purchase agreements and the way pharmaceutical companies have priced, negotiated, and delivered these supplies. Much of the focus of this debate has been on the vaccine supply ‘winners’ and ‘losers’, but the voices of public opinion have been more limited.MethodsWe explore the concepts of vaccine nationalism and internationalism from the perspective of vaccine trial participants, using an empirical perspectives study that involved interviews with phase I/II COVID-19 vaccine trial participants in Oxford, UK. We surveyed and interviewed participants between September and October 2020 about their views, motivations and experiences in taking part in the trial.ResultsFirst, we show how trial participants describe national and international ideas about vaccination as intertwined and challenge claims that these positions are mutually exclusive or oppositional. Second, we analyse these viewpoints further to show that vaccine nationalism is closely connected with national pride and metaphors of a country’s scientific achievements. Participants held a global outlook and were highly supportive of the prioritisation of vaccines by global need, but many were also pessimistic that such a solution could be possible.ConclusionTrial participants constitute an informed public group, with situated public expertise that the global community could draw on as an expert opinion. We argue that vaccine nationalism is strongly attached to national character and, therefore, it is more difficult for ownership of a vaccine to be thought of as international.

We present the Manually Annotated GONG Filaments in H-alpha Observations (MAGFiLO v1.0) dataset. This dataset contains 10,244 annotated filaments from 1,593 observations captured by the Global Oscillation Network Group (GONG), spanning the years 2011 through 2022. Each annotation details one filament’s segmentation, minimum bounding box, spine, and magnetic field chirality. With a total of over one thousand person-hours of annotation, and a double-blind review process, we ensured high-quality ground-truth data. Our inter-annotator agreement reaches a Kappa score of 0.66. We also verified that the hemispheric preference of filaments as annotated in MAGFiLO aligns with the findings from similar datasets of much smaller sample sizes. MAGFiLO is the first dataset of its size, enabling advanced deep learning models to identify filaments and their features with unprecedented precision. It also provides a testbed for solar physicists interested in large-scale analysis of filaments. In this report, we document the details of the annotation and the post-processing phases that were applied.

IntroductionPreparation for a future pandemic or serious epidemic caused by a known or yet unknown pathogen (Disease X) is a global health priority. Controlled human infection studies (CHIS) are recognised as a valuable tool to accelerate development of vaccines and immunotherapeutics against pathogens with pandemic potential and may play a role in future pandemic settings. The acceptability of CHIS to potential participants in a pandemic setting has not been explored.MethodsA mixed-methods study of adults screened to participate in a first-in-human SARS-CoV-2 vaccine trial, using online survey and interviews, was undertaken between September and October 2020 in Oxford, UK. This work assessed individuals’ views, motivations and experiences of participating in a trial during a pandemic setting, including attitudes towards a hypothetical SARS-CoV-2 CHIS.Results349 of 770 (45%) invited individuals completed the survey, and 102 survey respondents (29%) participated in a structured interview. Participants were highly educated, research informed and predominantly of white ethnicity. Approximately a third of survey respondents agreed they would be willing to participate in a hypothetical SARS-CoV-2 CHIS. Individuals aged <35 years old, those without children and those who were single were more likely to agree to participate in a hypothetical SARS-CoV-2 CHIS. This decision was dependent on short-term and long-term complications of infection, availability of rescue therapy, likelihood of CHIS to accelerate vaccine development and urgency of the public health need. Motivations to participate in a SARS-CoV-2 CHIS included altruism and a preference to acquire infection of a circulating pandemic pathogen in a controlled setting. The views of family and friends were important in individuals’ decision-making.ConclusionsVaccine trial participants are an informed and motivated public group who can provide situated public expertise for CHIS pandemic preparedness. Recruitment to CHIS in a pandemic may be more efficient if targeted to younger, single individuals without children. Media engagement and information specifically for potential CHIS participants’ families is important to facilitate informed discussion.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of Coronavirus Disease 2019 (COVID-19), has caused a global pandemic, and safe, effective vaccines are urgently needed 1 . Strong, Th1-skewed T cell responses can drive protective humoral and cell-mediated immune responses 2 and might reduce the potential for disease enhancement 3 . Cytotoxic T cells clear virus-infected host cells and contribute to control of infection 4 . Studies of patients infected with SARS-CoV-2 have suggested a protective role for both humoral and cell-mediated immune responses in recovery from COVID-19 (refs. 5 , 6 ). ChAdOx1 nCoV-19 (AZD1222) is a candidate SARS-CoV-2 vaccine comprising a replication-deficient simian adenovirus expressing full-length SARS-CoV-2 spike protein. We recently reported preliminary safety and immunogenicity data from a phase 1/2 trial of the ChAdOx1 nCoV-19 vaccine (NCT04400838) 7 given as either a one- or two-dose regimen. The vaccine was tolerated, with induction of neutralizing antibodies and antigen-specific T cells against the SARS-CoV-2 spike protein. Here we describe, in detail, exploratory analyses of the immune responses in adults, aged 18–55 years, up to 8 weeks after vaccination with a single dose of ChAdOx1 nCoV-19 in this trial, demonstrating an induction of a Th1-biased response characterized by interferon-γ and tumor necrosis factor-α cytokine secretion by CD4 + T cells and antibody production predominantly of IgG1 and IgG3 subclasses. CD8 + T cells, of monofunctional, polyfunctional and cytotoxic phenotypes, were also induced. Taken together, these results suggest a favorable immune profile induced by ChAdOx1 nCoV-19 vaccine, supporting the progression of this vaccine candidate to ongoing phase 2/3 trials to assess vaccine efficacy. A single dose of the ChAdOx1 nCoV-19 vaccine elicits antibodies and cytokine-producing T cells that might help control or prevent SARS-CoV-2 infection.

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.

Older adults (aged ≥70 years) are at increased risk of severe disease and death if they develop COVID-19 and are therefore a priority for immunisation should an efficacious vaccine be developed. Immunogenicity of vaccines is often worse in older adults as a result of immunosenescence. We have reported the immunogenicity of a novel chimpanzee adenovirus-vectored vaccine, ChAdOx1 nCoV-19 (AZD1222), in young adults, and now describe the safety and immunogenicity of this vaccine in a wider range of participants, including adults aged 70 years and older. In this report of the phase 2 component of a single-blind, randomised, controlled, phase 2/3 trial (COV002), healthy adults aged 18 years and older were enrolled at two UK clinical research facilities, in an age-escalation manner, into 18–55 years, 56–69 years, and 70 years and older immunogenicity subgroups. Participants were eligible if they did not have severe or uncontrolled medical comorbidities or a high frailty score (if aged ≥65 years). First, participants were recruited to a low-dose cohort, and within each age group, participants were randomly assigned to receive either intramuscular ChAdOx1 nCoV-19 (2·2 × 1010 virus particles) or a control vaccine, MenACWY, using block randomisation and stratified by age and dose group and study site, using the following ratios: in the 18–55 years group, 1:1 to either two doses of ChAdOx1 nCoV-19 or two doses of MenACWY; in the 56–69 years group, 3:1:3:1 to one dose of ChAdOx1 nCoV-19, one dose of MenACWY, two doses of ChAdOx1 nCoV-19, or two doses of MenACWY; and in the 70 years and older, 5:1:5:1 to one dose of ChAdOx1 nCoV-19, one dose of MenACWY, two doses of ChAdOx1 nCoV-19, or two doses of MenACWY. Prime-booster regimens were given 28 days apart. Participants were then recruited to the standard-dose cohort (3·5–6·5 × 1010 virus particles of ChAdOx1 nCoV-19) and the same randomisation procedures were followed, except the 18–55 years group was assigned in a 5:1 ratio to two doses of ChAdOx1 nCoV-19 or two doses of MenACWY. Participants and investigators, but not staff administering the vaccine, were masked to vaccine allocation. The specific objectives of this report were to assess the safety and humoral and cellular immunogenicity of a single-dose and two-dose schedule in adults older than 55 years. Humoral responses at baseline and after each vaccination until 1 year after the booster were assessed using an in-house standardised ELISA, a multiplex immunoassay, and a live severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) microneutralisation assay (MNA80). Cellular responses were assessed using an ex-vivo IFN-γ enzyme-linked immunospot assay. The coprimary outcomes of the trial were efficacy, as measured by the number of cases of symptomatic, virologically confirmed COVID-19, and safety, as measured by the occurrence of serious adverse events. Analyses were by group allocation in participants who received the vaccine. Here, we report the preliminary findings on safety, reactogenicity, and cellular and humoral immune responses. This study is ongoing and is registered with ClinicalTrials.gov, NCT04400838, and ISRCTN, 15281137. Between May 30 and Aug 8, 2020, 560 participants were enrolled: 160 aged 18–55 years (100 assigned to ChAdOx1 nCoV-19, 60 assigned to MenACWY), 160 aged 56–69 years (120 assigned to ChAdOx1 nCoV-19: 40 assigned to MenACWY), and 240 aged 70 years and older (200 assigned to ChAdOx1 nCoV-19: 40 assigned to MenACWY). Seven participants did not receive the boost dose of their assigned two-dose regimen, one participant received the incorrect vaccine, and three were excluded from immunogenicity analyses due to incorrectly labelled samples. 280 (50%) of 552 analysable participants were female. Local and systemic reactions were more common in participants given ChAdOx1 nCoV-19 than in those given the control vaccine, and similar in nature to those previously reported (injection-site pain, feeling feverish, muscle ache, headache), but were less common in older adults (aged ≥56 years) than younger adults. In those receiving two standard doses of ChAdOx1 nCoV-19, after the prime vaccination local reactions were reported in 43 (88%) of 49 participants in the 18–55 years group, 22 (73%) of 30 in the 56–69 years group, and 30 (61%) of 49 in the 70 years and older group, and systemic reactions in 42 (86%) participants in the 18–55 years group, 23 (77%) in the 56–69 years group, and 32 (65%) in the 70 years and older group. As of Oct 26, 2020, 13 serious adverse events occurred during the study period, none of which were considered to be related to either study vaccine. In participants who received two doses of vaccine, median anti-spike SARS-CoV-2 IgG responses 28 days after the boost dose were similar across the three age cohorts (standard-dose groups: 18–55 years, 20 713 arbitrary units [AU]/mL [IQR 13 898–33 550], n=39; 56–69 years, 16 170 AU/mL [10 233–40 353], n=26; and ≥70 years 17 561 AU/mL [9705–37 796], n=47; p=0·68). Neutralising antibody titres after a boost dose were similar across all age groups (median MNA80 at day 42 in the standard-dose groups: 18–55 years, 193 [IQR 113–238], n=39; 56–69 years, 144 [119–347], n=20; and ≥70 years, 161 [73–323], n=47; p=0·40). By 14 days after the boost dose, 208 (>99%) of 209 boosted participants had neutralising antibody responses. T-cell responses peaked at day 14 after a single standard dose of ChAdOx1 nCoV-19 (18–55 years: median 1187 spot-forming cells [SFCs] per million peripheral blood mononuclear cells [IQR 841–2428], n=24; 56–69 years: 797 SFCs [383–1817], n=29; and ≥70 years: 977 SFCs [458–1914], n=48). ChAdOx1 nCoV-19 appears to be better tolerated in older adults than in younger adults and has similar immunogenicity across all age groups after a boost dose. Further assessment of the efficacy of this vaccine is warranted in all age groups and individuals with comorbidities. UK Research and Innovation, National Institutes 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.

More than 190 vaccines are currently in development to prevent infection by the novel severe acute respiratory syndrome coronavirus 2. Animal studies suggest that while neutralizing antibodies against the viral spike protein may correlate with protection, additional antibody functions may also be important in preventing infection. Previously, we reported early immunogenicity and safety outcomes of a viral vector coronavirus vaccine, ChAdOx1 nCoV-19 (AZD1222), in a single-blinded phase 1/2 randomized controlled trial of healthy adults aged 18–55 years ( NCT04324606 ). Now we describe safety and exploratory humoral and cellular immunogenicity of the vaccine, from subgroups of volunteers in that trial, who were subsequently allocated to receive a homologous full-dose (SD/SD D56; n  = 20) or half-dose (SD/LD D56; n  = 32) ChAdOx1 booster vaccine 56 d following prime vaccination. Previously reported immunogenicity data from the open-label 28-d interval prime-boost group (SD/SD D28; n  = 10) are also presented to facilitate comparison. Additionally, we describe volunteers boosted with the comparator vaccine (MenACWY; n  = 10). In this interim report, we demonstrate that a booster dose of ChAdOx1 nCoV-19 is safe and better tolerated than priming doses. Using a systems serology approach we also demonstrate that anti-spike neutralizing antibody titers, as well as Fc-mediated functional antibody responses, including antibody-dependent neutrophil/monocyte phagocytosis, complement activation and natural killer cell activation, are substantially enhanced by a booster dose of vaccine. A booster dose of vaccine induced stronger antibody responses than a dose-sparing half-dose boost, although the magnitude of T cell responses did not increase with either boost dose. These data support the two-dose vaccine regime that is now being evaluated in phase 3 clinical trials. Two doses of the coronavirus disease 2019 vaccine ChAdOx1 nCoV-19 boost antibody responses and functions in phase 1/2 trial participants.

The media have played an important part in presenting arguments for and against vaccination. The potential for the media to influence public attitudes to vaccines is becoming increasingly crucial to address. To understand the differing roles and responsibilities in the communication of vaccine trials we draw insight from a retrospective study of 349 survey responses and 102 semi-structured interviews conducted in 2020 with participants in the United Kingdom's first-in-human clinical trial of the Oxford-AstraZeneca COVID-19 vaccine. We found that trial participants had mixed views as to whether their participation conferred responsibility to communicate more widely about their trial experiences. Some participants perceived themselves to have an altruistic obligation to communicate to the media about the trial, and others felt that those who did share their participation had ‘attention-seeking’ motives. When participants did speak out they preferred to do so anonymously. Frustration was also reported with sensationalised and false media stories. Social media was viewed as a means to accelerate misinformation or as a force for recruitment and public education about trials. Participants were pleased to see trial investigators and trial team playing prominent roles in the media and this instilled confidence in the vaccine and the trial. We discuss these evolving roles and responsibilities for trial communication, concentrating on the views of participants about experiences, opportunities, and risks. We argue that the pandemic has demonstrated the need for clinical trials to be made more transparent as a scientific practice that requires better public understanding and engagement. For high-profile vaccine trials we recommend; (1) explicit and comprehensive guidance aimed at all participants for interactions with the media; (2) prioritising having open and effectively expressed accounts of trial composition, processes, and participation; (3) offering support and a direct communication channel for journalists to report trials by utilising internal press officers to engage with journalists.

Analysis of the UK government's plans to increase health visitor numbers over the next 3 years. The health visitor role is described and reasons why numbers needs to be increased are considered, including rising birth rates and increased immigration. 0 references