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Different forms of vaccines have been developed to prevent the SARS-CoV-2 virus and subsequent COVID-19 disease. Several are in widespread use globally. OBJECTIVES: To assess the efficacy and safety of COVID-19 vaccines (as a full primary vaccination series or a booster dose) against SARS-CoV-2.We searched the Cochrane COVID-19 Study Register and the COVID-19 L·OVE platform (last search date 5 November 2021). We also searched the WHO International Clinical Trials Registry Platform, regulatory agency websites, and Retraction Watch.We included randomized controlled trials (RCTs) comparing COVID-19 vaccines to placebo, no vaccine, other active vaccines, or other vaccine schedules.We used standard Cochrane methods. We used GRADE to assess the certainty of evidence for all except immunogenicity outcomes. We synthesized data for each vaccine separately and presented summary effect estimates with 95% confidence intervals (CIs). MAIN RESULTS: We included and analyzed 41 RCTs assessing 12 different vaccines, including homologous and heterologous vaccine schedules and the effect of booster doses. Thirty-two RCTs were multicentre and five were multinational. The sample sizes of RCTs were 60 to 44,325 participants. Participants were aged: 18 years or older in 36 RCTs; 12 years or older in one RCT; 12 to 17 years in two RCTs; and three to 17 years in two RCTs. Twenty-nine RCTs provided results for individuals aged over 60 years, and three RCTs included immunocompromized patients. No trials included pregnant women. Sixteen RCTs had two-month follow-up or less, 20 RCTs had two to six months, and five RCTs had greater than six to 12 months or less. Eighteen reports were based on preplanned interim analyses. Overall risk of bias was low for all outcomes in eight RCTs, while 33 had concerns for at least one outcome. We identified 343 registered RCTs with results not yet available. This abstract reports results for the critical outcomes of confirmed symptomatic COVID-19, severe and critical COVID-19, and serious adverse events only for the 10 WHO-approved vaccines. For remaining outcomes and vaccines, see main text. The evidence for mortality was generally sparse and of low or very low certainty for all WHO-approved vaccines, except AD26.COV2.S (Janssen), which probably reduces the risk of all-cause mortality (risk ratio (RR) 0.25, 95% CI 0.09 to 0.67; 1 RCT, 43,783 participants; high-certainty evidence). Confirmed symptomatic COVID-19 High-certainty evidence found that BNT162b2 (BioNtech/Fosun Pharma/Pfizer), mRNA-1273 (ModernaTx), ChAdOx1 (Oxford/AstraZeneca), Ad26.COV2.S, BBIBP-CorV (Sinopharm-Beijing), and BBV152 (Bharat Biotect) reduce the incidence of symptomatic COVID-19 compared to placebo (vaccine efficacy (VE): BNT162b2: 97.84%, 95% CI 44.25% to 99.92%; 2 RCTs, 44,077 participants; mRNA-1273: 93.20%, 95% CI 91.06% to 94.83%; 2 RCTs, 31,632 participants; ChAdOx1: 70.23%, 95% CI 62.10% to 76.62%; 2 RCTs, 43,390 participants; Ad26.COV2.S: 66.90%, 95% CI 59.10% to 73.40%; 1 RCT, 39,058 participants; BBIBP-CorV: 78.10%, 95% CI 64.80% to 86.30%; 1 RCT, 25,463 participants; BBV152: 77.80%, 95% CI 65.20% to 86.40%; 1 RCT, 16,973 participants). Moderate-certainty evidence found that NVX-CoV2373 (Novavax) probably reduces the incidence of symptomatic COVID-19 compared to placebo (VE 82.91%, 95% CI 50.49% to 94.10%; 3 RCTs, 42,175 participants). There is low-certainty evidence for CoronaVac (Sinovac) for this outcome (VE 69.81%, 95% CI 12.27% to 89.61%; 2 RCTs, 19,852 participants). Severe or critical COVID-19 High-certainty evidence found that BNT162b2, mRNA-1273, Ad26.COV2.S, and BBV152 result in a large reduction in incidence of severe or critical disease due to COVID-19 compared to placebo (VE: BNT162b2: 95.70%, 95% CI 73.90% to 99.90%; 1 RCT, 46,077 participants; mRNA-1273: 98.20%, 95% CI 92.80% to 99.60%; 1 RCT, 28,451 participants; AD26.COV2.S: 76.30%, 95% CI 57.90% to 87.50%; 1 RCT, 39,058 participants; BBV152: 93.40%, 95% CI 57.10% to 99.80%; 1 RCT, 16,976 participants). Moderate-certainty evidence found that NVX-CoV2373 probably reduces the incidence of severe or critical COVID-19 (VE 100.00%, 95% CI 86.99% to 100.00%; 1 RCT, 25,452 participants). Two trials reported high efficacy of CoronaVac for severe or critical disease with wide CIs, but these results could not be pooled. Serious adverse events (SAEs) mRNA-1273, ChAdOx1 (Oxford-AstraZeneca)/SII-ChAdOx1 (Serum Institute of India), Ad26.COV2.S, and BBV152 probably result in little or no difference in SAEs compared to placebo (RR: mRNA-1273: 0.92, 95% CI 0.78 to 1.08; 2 RCTs, 34,072 participants; ChAdOx1/SII-ChAdOx1: 0.88, 95% CI 0.72 to 1.07; 7 RCTs, 58,182 participants; Ad26.COV2.S: 0.92, 95% CI 0.69 to 1.22; 1 RCT, 43,783 participants); BBV152: 0.65, 95% CI 0.43 to 0.97; 1 RCT, 25,928 participants). In each of these, the likely absolute difference in effects was fewer than 5/1000 participants. Evidence for SAEs is uncertain for BNT162b2, CoronaVac, BBIBP-CorV, and NVX-CoV2373 compared to placebo (RR: BNT162b2: 1.30, 95% CI 0.55 to 3.07; 2 RCTs, 46,107 participants; CoronaVac: 0.97, 95% CI 0.62 to 1.51; 4 RCTs, 23,139 participants; BBIBP-CorV: 0.76, 95% CI 0.54 to 1.06; 1 RCT, 26,924 participants; NVX-CoV2373: 0.92, 95% CI 0.74 to 1.14; 4 RCTs, 38,802 participants). For the evaluation of heterologous schedules, booster doses, and efficacy against variants of concern, see main text of review.Compared to placebo, most vaccines reduce, or likely reduce, the proportion of participants with confirmed symptomatic COVID-19, and for some, there is high-certainty evidence that they reduce severe or critical disease. There is probably little or no difference between most vaccines and placebo for serious adverse events. Over 300 registered RCTs are evaluating the efficacy of COVID-19 vaccines, and this review is updated regularly on the COVID-NMA platform (covid-nma.com). Implications for practice Due to the trial exclusions, these results cannot be generalized to pregnant women, individuals with a history of SARS-CoV-2 infection, or immunocompromized people. Most trials had a short follow-up and were conducted before the emergence of variants of concern. Implications for research Future research should evaluate the long-term effect of vaccines, compare different vaccines and vaccine schedules, assess vaccine efficacy and safety in specific populations, and include outcomes such as preventing long COVID-19. Ongoing evaluation of vaccine efficacy and effectiveness against emerging variants of concern is also vital.

Background Which components of the immune response to SARS-CoV-2 vaccination best protect against subsequent infection remains unclear. We explored SARS-CoV-2 specific antibody and B-cell responses post 3rd dose vaccine and their relationship to subsequent SARS-CoV-2 infection. Methods In a multicentre prospective cohort, adult subjects provided samples before and 14 days (d14) post 3rd dose vaccine with Pfizer-BioNTech 162b2. At 18-22 weeks post vaccine, subjects self-reported SARS-CoV-2 infection (confirmed by PCR or antigen test). We used electrochemiluminescence assays to quantify antibodies to SARS-CoV-2 spike subunit 1 (S1), subunit 2 (S2) and receptor-binding domain (RBD) in plasma (reported in WHO IU/mL). In a subset of subjects, we assessed SARS-CoV-2 specific differentiated B-cell (plasma cell) and memory B-cell responses from peripheral blood mononuclear cells. Unstimulated plasma cells, and memory B cells stimulated with R848 and IL2, were seeded on plates coated with RBD or full Spike antigen and antigen-specific responses measured by ELISpot (Mabtech ELISpot, Sweden). We compared between group differences by Wilcoxon signed rank or Mann–Whitney tests. Data are median [IQR] unless specified. Results Of 133 subjects (age 43 [32-50], 81.2% female (table 1), 77 subjects in the B-cell subgroup (table 2)), 47 (35.3%) reported SARS-CoV-2 infection post 3rd vaccine. Antibody titres, plasma cell and memory B-cell responses all increased significantly at d14 post 3rd vaccine (Table 1 & 2, all P< 0.001). Although d14 antibody titres did not differ in those with and without subsequent infection (table 1), those reporting subsequent infection had significantly lower d14 RBD-specific plasma cells and a lower proportion of RBD-specific memory B-cells (Figure 1a-b, both P< 0.05). Similar results were observed with full-spike-specific memory B-cell responses (Figure 1d). The differences persisted when the non-infected group was restricted only to those reporting a confirmed close contact (n=26). Conclusion Infection following 3rd dose vaccine is associated with lower d14 circulating and memory B cell responses, but not antibody titres, suggesting B-cell responses better predict protection against subsequent SARS-CoV-2 infection. Disclosures All Authors: No reported disclosures.

Background Quantifying neutralising capacity of circulating SARS-COV-2 antibodies is critical in evaluating protective humoral immune responses generated post-infection/post-vaccination. Here we describe a novel medium-throughput flow cytometry based micro-neutralisation assay to evaluate Neutralising Antibody (NAb) responses against live SARS-CoV-2 Wild Type (D641G) and Variants of Concern (VoC) in convalescent/vaccinated populations. Methods Micro-Neutralisation assay (Micro-NT) was performed in 96-well plates using clinical isolate 2019-nCoV/Italy-INMI1, D641G (SARS-CoV-2/human/IRL/AIIDV1446/2020) and/or VOCs Beta (SARS-CoV-2/human/IRL/AIIDV1752/2021) and Omicron (SARS-Cov-2/human/IRL/AIIDV2326/2021). Plasma samples (All Ireland Infectious Diseases (AIID) Cohort) were serially diluted (8 points, half-log) from 1/20 and pre-incubated with SARS-CoV-2 (1h, 37°C). Virus-plasma mixture were added onto VERO E6/VERO-E6 TMPRSS2 cells for 18h. Percentage infected cells was analysed by automated flow cytometry following trypsinisation, fixation and SARS-CoV-2 Nucleoprotein intracellular staining. Half-maximal Neutralisation Titres (NT50) was determined using four-parameter logistic regression. Our assay was compared to Plaque Reduction Neutralisation Test (PRNT) and validated against WHO anti-SARS-CoV-2 Immunoglobulin Standards. Results Using WHO Standards with low, medium or high anti-SARS-CoV-2 IgG, both Micro-NT and PRNT achieved comparable NT50 values (Table 1). Micro-NT was found to be highly reproducible (inter-assay CV of 11.39%). Screening 190 convalescent samples and 11 COVID-19 naive controls (AIID cohort) we achieved an assay sensitivity of 90% and specificity of 81%. We demonstrated that Micro-NT has broad dynamic range differentiating NT50s < 1/20 to > 1/5000 (Figure 1). We could also characterise immune-escape VoC, observing up to 10-fold reduction in NT50 against Beta (Figure 2). Table 1:NT50s of Low, Medium and High Titre Anti-SARS-CoV-2 IgG Standards measured against Live SARS-CoV-2 using PRNT and Micro-NT Neutralising Capacity of low, medium and high-titre anti-SARS-CoV-2 IgG (WHO, International Standards) against live SARS-CoV-2 (2019-nCoV/Italy-INMI1) measured using PRNT and Micro-NT Assays on Vero E6 cells, as well as the potency of NAbs in each sample in International Units (IU/ml) as determined by the WHO. Figure 1:Dynamic Range of Micro-NT Micro-NT has a broad Dynamic Range, distinguishing low (A), medium (B) and high (C) neutralising plasma samples against live SARS-CoV-2 (2019-nCoV/Italy-INMI1) from a cohort of COVID-19 convalescent individuals (AIID cohort), as well as negative samples from COVID-19 naïve samples (D). Graphs show 3 representative samples of each NT50 range. (E) shows the population distribution of 190 Convalescent plasma samples as measured by Micro-NT on Vero E6 cells. Figure 2:Reduced Neutralisation Capacities measured against SARS-CoV-2 VoC using Micro-NT Low (A), Medium (B) and High (C) anti-SARS-CoV-2 IgG (WHO Standards) show different neutralising capacities against WT (D614G) SARS-CoV-2 and variants Beta and Omicron, measured using Micro-NT on Vero-E6-TMPRSS2 cells. Conclusion Our flow-cytometry-based Micro-NT is a robust and reliable assay to quantify NAb titres, an important evaluation endpoint in clinical trials. It has higher throughput (96 well format versus 12 well) and reduced infection time (18h vs 48-96h) compared to the gold standard PRNT. Disclosures All Authors: No reported disclosures.

Background A wide array of assays to detect the serologic response to SARS-CoV-2 have been developed since the emergence of the pandemic. The majority of these are either qualitative or semi-quantitative, detect antibodies against one antigenic target, and are not adaptable to new antigens. Methods We developed a new, multiplex immunoassay to detect antibodies against the receptor binding domain, S1 and S2 spike subunits and nucleocapsid (N) antigens of SARS-CoV-2 (the CEPHR SARS-CoV-2 Serology Assay). This assay uses electrochemiluminescence technology which allows for a broad dynamic range, and a linker format which allows for the addition of new antigenic targets. We tested this assay on a series of biobanked samples and validated its performance against the Abbott SARS-CoV-2 IgG and Abbott SARS-CoV-2 IgG II assays, and the MesoScale Diagnostics V-PLEX SARS-CoV-2 Panel 2 Kit. Results Participant demographics are shown in Table 1. The mean (standard deviation (SD)) intra-assay (within plate) coefficient of variation (CV) of 80 plasma samples run on the same plate was 3.9% (2.9) for N, 3.8% (6.2) for RBD, 3.8% (5.9) for S1 and 3.9% (5.3) for S2. The mean (SD) inter-assay CV derived from 5 samples run across 3 days by two different operators was 11% (6.5) for N, 13% (5.7) for RBD, 14% (8.9) for S1 and 13% (5.1) for S2. In the convalescent group (n=193), overall sensitivity for each assay was; RBD 82% (95% CI 76-87), S1 86% (81-91%), S2 88% (83 – 92%) and N 72% (64 – 78%). Sensitivity improved when analysis included only individuals who were sampled more than 14 days from onset of symptoms (n=166), RBD 87% (81 – 95%), S1 91% (85 – 95%), S2 91% (85 – 95%) but not for the N-target (73% (66-80%)). In vaccinated individuals (n = 58), 100% (94-100%) had both detectable RBD and S1 antibodies. Overall specificity was 96% (87-99%) for RBD, 90% (78-97%) for S1, 94% (84-99%) for S2 and 90% (78-97%) for N. There was excellent correlation between the Abbott IgG II and both CEPHR anti-RBD IgG (rho 0.91) and CEPHR anti-S1 IgG (rho 0.9, both p < 0.001, Figure 1.) and the V-PLEX full spike and both CEPHR RBD IgG (rho 0.83) and S1 IgG (rho 0.82, both p < 0.001, Figure 4). Table 1Participant demographics Correlation between CEPHR RBD, Abbott SARS-CoV-2 IgG II anti spike assay and V-PLEX Spike assay. Vertical dashed line represents CEPHR RBD positivity threshold, horizontal dashed line indicates Abbott positivity threshold. B: Correlation between CEPHR RBD and MSD V-PLEX Spike IgG. Vertical dashed line represents CEPHR RBD positivity threshold, no positivity threshold provided by MSD. Conclusion The CEPHR SARS-CoV-2 Serology Assay is a robust, customisable, multiplex serologic assay for the detection of several different IgG specific to SARS-CoV-2. Disclosures All Authors: No reported disclosures.

BACKGROUND The pan-European VACCELERATE network aims to implement the first transnational harmonized and sustainable vaccine trial Volunteer Registry, being a single entry point for potential volunteers of large-scale vaccine trials across Europe. This work exhibits a set of harmonized vaccine trial–related educational and promotional tools for the general public, designed and disseminated by the pan-European VACCELERATE network. OBJECTIVE This study primarily aimed to design and develop a standard toolkit to increase positive attitudes and access to trustworthy information for better access and increased recruitment to vaccine trials for the public. More specifically, the produced tools are focused on inclusiveness and equity, and are targeting different population groups, including underserved ones, as potential volunteers for the VACCELERATE Volunteer Registry (older individuals, migrants, children, and adolescents). The promotional and educational material is aligned with the main objectives of the Volunteer Registry to increase public literacy and awareness regarding vaccine-related clinical research or trials and trial participation, including informed consent and legal issues, side effects, and frequently asked questions regarding vaccine trial design. METHODS Tools were developed per the aims and principles of the VACCELERATE project, focusing on trial inclusiveness and equity, and are adjusted to local country-wise requirements to improve public health communication. The produced tools are selected based on the cognitive theory, inclusiveness, and equity of differently aged and underrepresented groups, and standardized material from several official trustworthy sources (eg, COVID-19 Vaccines Global Access; the European Centre for Disease Prevention and Control; the European Patients’ Academy on Therapeutic Innovation; Gavi, the Vaccine Alliance; and the World Health Organization). A team of multidisciplinary specialists (infectious diseases, vaccine research, medicine, and education) edited and reviewed the subtitles and scripts of the educational videos, extended brochures, interactive cards, and puzzles. Graphic designers selected the color palette, audio settings, and dubbing for the video story-tales and implemented QR codes. RESULTS This study presents the first set of harmonized promotional and educational materials and tools (ie, educational cards, educational and promotional videos, extended brochures, flyers, posters, and puzzles) for vaccine clinical research (eg, COVID-19 vaccines). These tools inform the public about possible benefits and disadvantages of trial participation and build confidence among participants about the safety and efficacy of COVID-19 vaccines and the health care system. This material has been translated into several languages and is intended to be freely and easily accessible to facilitate dissemination among VACCELERATE network participant countries and the European and global scientific, industrial, and public community. CONCLUSIONS The produced material could help fill knowledge gaps of health care personnel, providing the appropriate future patient education for vaccine trials, and tackling vaccine hesitancy and parents’ concerns for potential participation of children in vaccine trials.

Summary Background In DISCOVER, a multinational, randomised controlled trial, emtricitabine and tenofovir alafenamide compared with emtricitabine and tenofovir disoproxil fumarate showed non-inferior efficacy for HIV prevention and improved bone mineral density and renal safety biomarkers at week 48. We report outcomes analysed after all participants had completed 96 weeks of follow-up. Methods This study is an ongoing, randomised, double-blind, multicentre, active-controlled, phase 3, non-inferiority trial done at 94 community, public health, and hospital-associated clinics located in Europe and North America. Adult cisgender men and transgender women who have sex with men, both with a high risk of acquiring HIV as determined by self-reported sexual behaviour or recent sexually transmitted infections, were randomly assigned (1:1) to receive either emtricitabine and tenofovir alafenamide (200/25 mg) tablets daily, with matched placebo tablets (emtricitabine and tenofovir alafenamide group), or emtricitabine and tenofovir disoproxil fumarate (200/300 mg) tablets daily, with matched placebo tablets (emtricitabine and tenofovir disoproxil fumarate group). The primary efficacy outcome was incident HIV infection. Incidence of HIV-1 infection per 100 person-years was assessed when the last participant had completed 96 weeks of follow-up. This trial is registered with ClinicalTrials.gov , number NCT02842086 . Findings Between Sept 13, 2016, and June 30, 2017, 5387 participants were randomly assigned to receive emtricitabine and tenofovir alafenamide (n=2694) or emtricitabine and tenofovir disoproxil fumarate (n=2693), contributing 10 081 person-years of follow-up. At 96 weeks of follow-up, there were eight HIV infections in participants who had received emtricitabine and tenofovir alafenamide (0·16 infections per 100 person-years [95% CI 0·07–0·31]) and 15 in participants who had received emtricitabine and tenofovir disoproxil fumarate (0·30 infections per 100 person-years [0·17–0·49]). Emtricitabine and tenofovir alafenamide maintained its non-inferiority to emtricitabine and tenofovir disoproxil fumarate for HIV prevention (IRR 0·54 [95% CI 0·23–1·26]). Approximately 78–82% of participants reported taking study medication more than 95% of the time across all study visits. Rates of sexually transmitted infections remained high and similar across groups (21 cases per 100 person-years for rectal gonorrhoea and 28 cases per 100 person-years for rectal chlamydia). Emtricitabine and tenofovir alafenamide continued to show superiority over emtricitabine and tenofovir disoproxil fumarate in all but one of the six prespecified bone mineral density and renal biomarkers. There was more weight gain among participants who had received emtricitabine and tenofovir alafenamide (median weight gain 1·7 kg vs 0·5 kg, p Interpretation Emtricitabine and tenofovir alafenamide is safe and effective for longer-term pre-exposure prophylaxis in cisgender men and transgender women who have sex with men. Funding Gilead Sciences.

Introduction Sleep problems are commonly reported in people with HIV (PWH) and may be exacerbated by HIV-induced inflammation. We determined associations between systemic inflammation and objective/subjective sleep measures in PWH and demographically/lifestyle similar HIV-negative controls. Methods Objective sleep measures from 7-day actigraphy (e.g. mean/standard deviation (SD) of wake after sleep onset [WASO], sleep duration/efficiency), overnight oximetry (oxygen desaturation index [ODI]), and patient-reported measures (Insomnia Severity Index [ISI] and Patient-Reported Outcomes Measurement Information System [PROMIS] sleep questionnaires) were assessed in participants in the multicenter POPPY-Sleep Study in the UK and Ireland. Principal Component Analysis using 31 plasma inflammatory biomarkers followed by cluster analysis previously identified 3 distinct inflammatory clusters: 1 (low inflammation), 2 (immune activation) and 3 (systemic inflammation). Baseline characteristics and between-cluster differences in sleep outcomes were assessed using Kruskal-Wallis or logistic regression/Chi-squared tests. Results The 465 participants (74% PWH, median [interquartile range] age 54 [50-60] years) were mainly male (80%), men having sex with men (71%) and white (88%). Among PWH, most (98%) were on antiretroviral therapy, 92% had viral load ≤50 cps/mL and CD4 cell count was 610 [470-785] cells/mm3. Overall, 18% met ISI criteria for insomnia (ISI≥ 15), and other sleep measures suggested generally good sleep (e.g., ODI 3.1/hr [1.5-6.4]). Clusters 1 (n=209), 2 (n=47) and 3 (n=209) differed significantly for HIV status (73%, 60%, 78%, p=0.03); BMI (24.8, 25.9, 26.2 kg/m2, p=0.002); systolic blood pressure (126, 135, 126 mmHg, p=0.002); cardiovascular disease (39%, 28%, 53%, p=0.001) and arthritis (8%, 9%,16%, p=0.02) – all factors associated with sleep problems. There were no clinically relevant between-biomarker-cluster differences in the proportions with insomnia (17%, 18%, 20%) either before (p=0.76) or after (p=0.75) adjustment for potential confounders. Few associations were observed among other actigraphy, oximetry and PROMIS measures. Conclusion Despite observed differences in clinical factors associated with sleep problems, we found no consistent or strong associations between inflammatory biomarker clusters and a range of sleep outcomes. Although associations could exist with other sleep outcomes (e.g. sleep architecture) or biomarker types (e.g. cerebrospinal fluid) not assessed, our findings do not support a strong association between sleep and plasma inflammatory biomarkers in this population. Support (If Any) NIH R01HL131049

Background: Although reports suggest that most individuals with COVID-19 develop detectable antibodies post infection, the kinetics, durability, and relative differences between IgM and IgG responses beyond the first few weeks after symptom onset remain poorly understood. Methods: Within a large, well-phenotyped, diverse, prospective cohort of subjects with and without SARS-CoV-2 PCR-confirmed infection and historical controls derived from cohorts with high prevalence of viral coinfections and samples taken during prior flu seasons, we measured SARS-CoV-2 serological responses (both IgG and IgM) using commercially available assays. We calculated sensitivity and specificity, relationship with disease severity and mapped the kinetics of antibody seropositivity and antibody levels over time using generalised additive models. Findings: We analysed 1,001 samples from 752 subjects, 327 with confirmed SARS-CoV-2 (29.7% with severe disease) spanning a period of 90 days from symptom onset. Sensitivity was lower (44.1-47.1%) early ( 80% after 10 days. IgM positivity increased earlier than IgG-targeted assays but positivity peaked between day 32 and 38 post onset of symptoms and declined thereafter, a dynamic that was confirmed when antibody levels were analysed, with more rapid decline observed with IgM. Early (

Thermoforming, a commonly used method to manufacture components from fibre reinforced thermoplastic laminates, involves heating the composite to its melt/softening temperature and then applying suitable forces to mould the composite to the required shape. Acquiring complex curvature shapes involves flow phenomena such as interply slip, intraply shear and squeeze flow. To date, the intraply shear mechanism is the least well understood. Approaches have been made to determine both longitudinal and transverse steady intraply shear viscosities of molten unidirectional continuous fibre-reinforced composites in the past but with conflicting results. No truly comprehensive characterisation has been carried out on these materials under a steady shear rate deformation mode. The present study concentrated on experimentally establishing the intraply shear behaviour of carbon fibre reinforced polyetheretherketone (APC-2). Two basic orientations were considered, one where the fibres in the lay-up were parallel to the pull-out direction and the other where the fibres were perpendicular to the pull-out direction. Values of longitudinal and transverse shear viscosities were determined for shear rates between 0.002 and 0.02 s −1 . The viscosity was highly shear-rate dependent, and was best modelled using a ‘power-law’. At a rate of 0.01 s −1 the longitudinal viscosity was in the 1 MPa s range, and approximately 2.5 times the transverse value. These values are several orders of magnitude greater than those determined using more traditional means, such as torsional rheometry, but agree with results obtained using a picture frame test method.

A literature survey is presented on sheet-forming methods and mechanisms for continuous fiber reinforced thermoplastics. The diaphragm forming process is shown to be one of the more promising fabrication routes for complex-curvature structures. The primary deformation mechanisms involved in the sheet-forming processes are identified and discussed. Earlier approaches to develop mathematical models either have been kinematically based or have treated only one of the primary deformation mechanisms. A promising constitutive model for the highly anisotropic behavior of the composite at forming temperature is examined. The composite sheet is assumed to behave as a transversely isotropic Newtonian fluid that is both incompressible and inextensible in the fiber direction. The second section of the paper treats the experimental development of the polymeric diaphragm forming process for thermoplastic composites. The viscoelastic properties of the diaphragm material are characterized by dynamic mechanical analysis. The rate sensitivity of the phenomenon of shear-buckling during forming of certain cross-ply and quasi-isotropic composite laminates is investigated, using a shallow female mold. Finally, the interface condition between the diaphragm and the composite during forming is examined.

An experimental autoclave with a forming rate control system and sophisticated data acquisition facilities has been employed for polymeric diaphragm form ing of carbon fibre reinforced polyetheretherketone (PEEK). Central displacement mea surements were recorded using a high temperature linear variable differential transformer (LVDT), while forming into a hemispherical mould. Using this facility the pressure versus displacement relationships were established for Upilex-R, Upilex-S, and Kapton-H and superplastic aluminium (Supral) diaphragms. Both Upilex-S and Kapton-H were found to have similar stiffness values, about eight times greater than Upilex-R, while the Supral is about sixteen times stiffer than Upilex-R. Pressure versus displacement characteristics are reported for (0°)8, (0°)16, (0°/90°) 2 s, (0°/90°)4 s and (0°/+45°/-45°/90°) s carbon fibre reinforced PEEK (APC-2) layups, which show that the laminate stiffness at forming tem perature is very low relative to the diaphragm stiffness of Upilex-S, Kapton or Supral. The effect of diaphragm stiffness on squeeze flow is clearly demonstrated as the stiffer di aphragms, Upilex-S and Supral, require higher pressures to complete the forming and consequently cause increased squeeze flow over that shown when using Upilex-R. How ever, it has also been demonstrated that the use of these stiffer diaphragms reduces the risk of laminate buckling. When forming with Upilex-R diaphragms, out of plane buckling was eliminated for a (0°/+45°/-45°/90°), APC-2 layup by reducing the forming rate to 6 mm/mm

Dielectric Analysis (DEA) is a widely used method to measure the cure of many common thermosetting resins systems such as epoxies, polyesters, polyurethanes, polyimides, silicones, bismaleimides and phenolics. The objective of this work is to investigate the curing characteristics of a thermoplastic, Cyclic Butylene Terephthalate (CBT) (supplied by Cyclics Corporation) which polymerises to form Polybutylene Terephthalate (PBT). This paper reports on the results of ongoing experimental investigations in which DEA is used to relate the curing cycle to composite structural features and mechanical performance of a complex composite part. Through adjustments in curing parameters, the significant processing parameters have been identified which optimise the production cycle for thermoplastic PBT composite parts. The recorded ion viscosity is used to determine change in material viscosity, cure rate and cure time. These results have been analysed and presented as a processing guide for correct process control.

An experimental programme on diaphragm forming of thermoplastic composite laminates has successfully demonstrated the critical deformation mechanisms which occur during the forming stage of the process. Both single and complex curvature parts were formed in an experimental autoclave which had sophisticated process control facilities for the independent control of both pressurisation and forming rates. When a 90° bend was formed into a female mould the mechanism of interply slip was clearly demonstrated. These 90° bends were formed from both unidirectional and cross ply layups of APC-2 and in all cases the degree of post forming spring forward was between 1.5° and 2.5°. The factors which influence laminate buckling during the forming of complex curvature components were shown to be; the rate of forming, the ratio of layup area to the forming area and the stiffness of the diaphragms. The higher forming pressures required for the suffer diaphragms indirectly caused severe squeeze flow and surface ply erosion. The latter effect was alleviated by the use of a slip ply between the laminate and the diaphragm in single curvature parts.

An experimental autoclave has been designed and commissioned for polymeric diaphragm forming of continuous fibre-reinforced thermoplastic composite parts. The stand-alone autoclave is heated using a standard heater band and is pressurized by compressed nitrogen gas. Unidirectional and cross-ply stacked prepregs of carbon fibre-reinforced polyetheretherketone have been successfully formed over a 90° single-curvature bend. Forming is effected by applying differential pressures across a double polyimide diaphragm. Innovative tool design, resulting in cheap and light mould construction, combined with transfer gas cooling under pressure, gives cycle times of 75 minutes. Part reproducibility and quality is confirmed by nondestructive evaluation. Commercial opportunities for polymeric diaphragm forming techniques with thermoplastic composites are also discussed.

Dielectric analysis (DEA) is the most common technique used to determine the state of cure in-process for many thermosetting resins systems such as epoxies, polyesters, polyurethanes, polyimides, silicones, bismaleimides, and phenolics. The objective of this work is to investigate the processing characteristics of cyclic butylene terephthalate (CBT) (supplied by Cyclics Corporation) which polymerises to form a thermoplastic, polybutylene terephthalate (PBT). This paper reports on the interim results of ongoing experimental investigations in which DEA is used to correlate the process cycle to composite structural features and mechanical performance of a complex composite part. Through adjustments in process cycle, the significant processing parameters have been identified which optimise the production of thermoplastic PBT composite parts. The recorded ion viscosity is used to indicate change in material viscosity, conversion rate and process time. These results have been analysed and presented as a guide for correct process control.

Background The pan-European VACCELERATE network aims to implement the first transnational harmonized and sustainable vaccine trial Volunteer Registry, being a single entry point for potential volunteers of large-scale vaccine trials across Europe. This work exhibits a set of harmonized vaccine trial–related educational and promotional tools for the general public, designed and disseminated by the pan-European VACCELERATE network. Objective This study primarily aimed to design and develop a standard toolkit to increase positive attitudes and access to trustworthy information for better access and increased recruitment to vaccine trials for the public. More specifically, the produced tools are focused on inclusiveness and equity, and are targeting different population groups, including underserved ones, as potential volunteers for the VACCELERATE Volunteer Registry (older individuals, migrants, children, and adolescents). The promotional and educational material is aligned with the main objectives of the Volunteer Registry to increase public literacy and awareness regarding vaccine-related clinical research or trials and trial participation, including informed consent and legal issues, side effects, and frequently asked questions regarding vaccine trial design. Methods Tools were developed per the aims and principles of the VACCELERATE project, focusing on trial inclusiveness and equity, and are adjusted to local country-wise requirements to improve public health communication. The produced tools are selected based on the cognitive theory, inclusiveness, and equity of differently aged and underrepresented groups, and standardized material from several official trustworthy sources (eg, COVID-19 Vaccines Global Access; the European Centre for Disease Prevention and Control; the European Patients’ Academy on Therapeutic Innovation; Gavi, the Vaccine Alliance; and the World Health Organization). A team of multidisciplinary specialists (infectious diseases, vaccine research, medicine, and education) edited and reviewed the subtitles and scripts of the educational videos, extended brochures, interactive cards, and puzzles. Graphic designers selected the color palette, audio settings, and dubbing for the video story-tales and implemented QR codes. Results This study presents the first set of harmonized promotional and educational materials and tools (ie, educational cards, educational and promotional videos, extended brochures, flyers, posters, and puzzles) for vaccine clinical research (eg, COVID-19 vaccines). These tools inform the public about possible benefits and disadvantages of trial participation and build confidence among participants about the safety and efficacy of COVID-19 vaccines and the health care system. This material has been translated into several languages and is intended to be freely and easily accessible to facilitate dissemination among VACCELERATE network participant countries and the European and global scientific, industrial, and public community. Conclusions The produced material could help fill knowledge gaps of health care personnel, providing the appropriate future patient education for vaccine trials, and tackling vaccine hesitancy and parents’ concerns for potential participation of children in vaccine trials.