Efficacy of heterologous boosting against SARS-CoV-2 using a recombinant interferon-armed fusion protein vaccine (V-01): a randomized, double-blind and placebo-controlled phase III trial.

Waning of neutralizing titres along with decline of protection efficacy after the second dose of COVID-19 vaccines was observed, including China-made inactivated vaccines. Efficacy of a heterologous boosting using one dose of a recombinant SARS-CoV-2 fusion protein vaccine (V-01) in inactivated vaccine-primed population was studied, aimed to restore the immunity. A randomized, double-blind and placebo-controlled phase III trial was conducted in healthy people aged 18 years or older in Pakistan and Malaysia. Each eligible participant received one dose of the V-01 vaccine developed by Livzon Mabpharm Inc. or placebo within the 3-6 months after the two-dose primary regimen, and was monitored for safety and efficacy. The primary endpoint was protection against confirmed symptomatic SARS-CoV-2 infection. A total of 10,218 participants were randomly assigned to receive a vaccine or placebo. Virus-neutralizing antibodies were assessed in 419 participants. A dramatic increase (11.3-fold; 128.3-1452.8) of neutralizing titres was measured in the V-01 group at 14 days after the booster. Over two months of surveillance, vaccine efficacy was 47.8% (95%CI: 22.6-64.7) according to the intention-to-treat principle. The most common adverse events were transient, mild-to-moderate pain at the injection site, fever, headache, and fatigue. Serious adverse events occurred almost equally in V-01 (0.12%) and placebo (0.16%) groups. The heterologous boosting with the V-01 vaccine was safe and efficacious, which could elicit robust humoral immunity under the epidemic of the Omicron variant.Trial registration: ClinicalTrials.gov identifier: NCT05096832.

Immunogenicity and safety of a recombinant fusion protein vaccine (V-01) against coronavirus disease 2019 in healthy adults: a randomized, double-blind, placebo-controlled, phase II trial.

BACKGROUND: Innovative coronavirus disease 2019 (COVID-19) vaccines, with elevated global manufacturing capacity, enhanced safety and efficacy, simplified dosing regimens, and distribution that is less cold chain-dependent, are still global imperatives for tackling the ongoing pandemic. A previous phase I trial indicated that the recombinant COVID-19 vaccine (V-01), which contains a fusion protein (IFN-PADRE-RBD-Fc dimer) as its antigen, is safe and well tolerated, capable of inducing rapid and robust immune responses, and warranted further testing in additional clinical trials. Herein, we aimed to assess the immunogenicity and safety of V-01, providing rationales of appropriate dose regimen for further efficacy study. METHODS: A randomized, double-blind, placebo-controlled phase II clinical trial was initiated at the Gaozhou Municipal Centre for Disease Control and Prevention (Guangdong, China) in March 2021. Both younger (n = 440; 18-59 years of age) and older (n = 440; ≥60 years of age) adult participants in this trial were sequentially recruited into two distinct groups: two-dose regimen group in which participants were randomized either to follow a 10 or 25 µg of V-01 or placebo given intramuscularly 21 days apart (allocation ratio, 3:3:1, n = 120, 120, 40 for each regimen, respectively), or one-dose regimen groups in which participants were randomized either to receive a single injection of 50 µg of V-01 or placebo (allocation ratio, 3:1, n = 120, 40, respectively). The primary immunogenicity endpoints were the geometric mean titers of neutralizing antibodies against live severe acute respiratory syndrome coronavirus 2, and specific binding antibodies to the receptor binding domain (RBD). The primary safety endpoint evaluation was the frequencies and percentages of overall adverse events (AEs) within 30 days after full immunization. RESULTS: V-01 provoked substantial immune responses in the two-dose group, achieving encouragingly high titers of neutralizing antibody and anti-RBD immunoglobulin, which peaked at day 35 (161.9 [95% confidence interval [CI]: 133.3-196.7] and 149.3 [95%CI: 123.9-179.9] in 10 and 25 µg V-01 group of younger adults, respectively; 111.6 [95%CI: 89.6-139.1] and 111.1 [95%CI: 89.2-138.4] in 10 and 25 µg V-01 group of older adults, respectively), and remained high at day 49 after a day-21 second dose; these levels significantly exceed those in convalescent serum from symptomatic COVID-19 patients (53.6, 95%CI: 31.3-91.7). Our preliminary data show that V-01 is safe and well tolerated, with reactogenicity predominantly being absent or mild in severity and only one vaccine-related grade 3 or worse AE being observed within 30 days. The older adult participants demonstrated a more favorable safety profile compared with those in the younger adult group: with AEs percentages of 19.2%, 25.8%, 17.5% in older adults vs. 34.2%, 23.3%, 26.7% in younger adults at the 10, 25 µg V-01 two-dose group, and 50 µg V-01 one-dose group, respectively. CONCLUSIONS: The vaccine candidate V-01 appears to be safe and immunogenic. The preliminary findings support the advancement of the two-dose, 10 µg V-01 regimen to a phase III trial for a large-scale population-based evaluation of safety and efficacy. TRIAL REGISTRATION: http://www.chictr.org.cn/index.aspx (No. ChiCTR2100045107, http://www.chictr.org.cn/showproj.aspx?proj=124702).

Improving participation and engagement with a COVID-19 surveillance programme in an outpatient setting.

BACKGROUND: On 3 August 2020, Public Health Scotland commenced a prospective surveillance study to monitor the prevalence of COVID-19 among asymptomatic outpatients attending dental clinics across 14 health boards in Scotland. OBJECTIVES: The primary aim of this quality improvement project was to increase the number of COVID-19 tests carried out in one of the participating sites, Glasgow Dental Hospital and School. The secondary aim was to identify barriers to patient participation and staff engagement when implementing a public health initiative in an outpatient setting. METHOD: A quality improvement working group met weekly to discuss hospital findings, identify drivers and change ideas. Details on reasons for patient non-participation were recorded and questionnaires on project barriers were distributed to staff. In response to findings, rapid interventions were implemented to fast-track increases in the numbers of tests being carried out. RESULTS: Over 16 weeks, 972 tests were carried out by Glasgow Dental Hospital and School Secondary Care Services. The number of tests per week increased from 19 (week 1) to 129 (week 16). This compares to a similar 'control' site, where the number of tests carried out remained unchanged; 38 (week 1) to 36 (week 16). The most frequent reason given for non-participation was fear that the swab would hurt. For staff, lack of time and forgetting to ask patients were identified as the most significant barriers. CONCLUSION: Public health surveillance programmes can be integrated rapidly into outpatient settings. This project has shown that a quality improvement approach can be successful in integrating such programmes. The key interventions used were staff engagement initiatives and front-line data collection. Implementation barriers were also identified using staff questionnaires.

Impact of COVID-19 Lockdown on Physical Activity Among the Chinese Youths: The COVID-19 Impact on Lifestyle Change Survey (COINLICS).

Background: The study sought to assess the changes in physical activity (PA) and sedentary time among Chinese youths at different stages after the COVID-19 outbreak. Methods: It was based on a retrospective online survey conducted in May 2020. More than 10,000 youths voluntarily recalled their PA-related information at three stages: before COVID-19 (January), during lockdown (February), and after lockdown (May). χ2 tests were conducted to evaluate the significance of the differences in participants' characteristics between sexes, and Wilcoxon Rank Sum tests were performed to examine the significance of differences in changes in PA and sedentary behavior levels between sexes. Results: A total of 8,115 participants were included, with a mean age of 20. The percentage of no PA per week increased significantly and then slightly fell, and that of ≥150 min/week substantially decreased and then rebounded partially (all p < 0.001) (for instance, the percentage of ≥150 min/week of PA total decreased from 38.6 to 19.4%, then rebounded back to 25.3%). Means hours per day spent in sedentary behaviors had significantly increased during lockdown comparing to pre-COVID-19 (all p < 0.001). There were more participants reported reduced PA level than those indicated increased, and more participating youths had their sedentary behavior level increased than those who had it decreased. Conclusions: The study found COVID-19 had both immediate and longer-term impacts on self-reported physical activities and sedentary behaviors among Chinese youths. Relevant efforts should be strengthened to get youths physically moving again.

Identification of SARS-CoV-2 entry inhibitors among already approved drugs.

To discover effective drugs for COVID-19 treatment amongst already clinically approved drugs, we developed a high throughput screening assay for SARS-CoV-2 virus entry inhibitors using SARS2-S pseudotyped virus. An approved drug library of 1800 small molecular drugs was screened for SARS2 entry inhibitors and 15 active drugs were identified as specific SARS2-S pseudovirus entry inhibitors. Antiviral tests using native SARS-CoV-2 virus in Vero E6 cells confirmed that 7 of these drugs (clemastine, amiodarone, trimeprazine, bosutinib, toremifene, flupenthixol, and azelastine) significantly inhibited SARS2 replication, reducing supernatant viral RNA load with a promising level of activity. Three of the drugs were classified as histamine receptor antagonists with clemastine showing the strongest anti-SARS2 activity (EC50 = 0.95 ± 0.83 µM). Our work suggests that these 7 drugs could enter into further in vivo studies and clinical investigations for COVID-19 treatment.