Safety and immunogenicity of a SARS-CoV-2 recombinant protein nanoparticle vaccine (GBP510) adjuvanted with AS03: A randomised, placebo-controlled, observer-blinded phase 1/2 trial.

Background: Vaccination has helped to mitigate the COVID-19 pandemic. Ten traditional and novel vaccines have been listed by the World Health Organization for emergency use. Additional alternative approaches may better address ongoing vaccination globally, where there remains an inequity in vaccine distribution. GBP510 is a recombinant protein vaccine, which consists of self-assembling, two-component nanoparticles, displaying the receptor-binding domain (RBD) in a highly immunogenic array. Methods: This randomised, placebo-controlled, observer-blinded phase 1/2 study was conducted to evaluate the safety and immunogenicity of GBP510 (2-doses at a 28-day interval) adjuvanted with or without AS03 in adults aged 19-85 years at 14 hospital sites in Korea. This study was consisted of two stages (stage I, healthy adults aged 19-55 years; stage II, 240 healthy adults aged 19-85 years). Healthy participants who did not previously receive any vaccine within 4 weeks (2 weeks for flu vaccine) prior to the study, no history of COVID-19 vaccination/medication, and were naïve to SARS-CoV-2 infection at screening were eligible for the study enrollment. Participants were block-randomized in a 2:2:1 ratio to receive 2 doses of 10 µg GBP510 adjuvanted with AS03 (group 1), 10 µg unadjuvanted GBP510 (group 2) or placebo intramuscularly in stage I, while they were block-randomized in a 2:2:1:1 ratio to receive 10 µg GBP510 adjuvanted with AS03 (group 1), 25 µg GBP510 adjuvanted with AS03 (group 3), 25 µg unadjuvanted GBP510 (group 4) or placebo in stage II. The primary safety outcomes were solicited and unsolicited adverse events, while primary immunogenicity outcomes included anti-SARS-CoV-2 RBD IgG antibodies; neutralizing antibody responses; and T-cell immune responses. Safety assessment included all participants who received at least 1 dose of study intervention (safety set). Immunogenicity assessment included all participants who completed the vaccination schedule and had valid immunogenicity assessment results without any major protocol deviations (per-protocol set). This study was registered with ClinicalTrials.gov (NCT04750343). Findings: Of 328 participants who were enrolled between February 1 and May 28, 2021, 327 participants received at least 1 dose of vaccine. Each received either 10 µg GBP510 adjuvanted with AS03 (Group 1, n = 101), 10 µg unadjuvanted GBP510 (Group 2, n = 10), 25 µg GBP510 adjuvanted with AS03 (Group 3, n = 104), 25 µg unadjuvanted GBP510 (Group 4, n = 51), or placebo (n = 61). Higher reactogenicity was observed in the GBP510 adjuvanted with AS03 groups compared to the non-adjuvanted and placebo groups. The most frequently reported solicited local adverse event (AE) was injection site pain after any vaccination: (88·1% in group 1; 50·0% in group 2; 92·3% in group 3; 66·7% in group 4). Fatigue and myalgia were two most frequently reported systemic AEs and more frequently reported in GBP510 adjuvanted with AS03 recipients (79·2% and 78·2% in group 1; 75·0% and 79·8% in group 3, respectively) than in the unadjuvanted vaccine recipients (40·0% and of 40·0% in group 2; 60·8% and 47·1% in group 4) after any vaccination. Reactogenicity was higher post-dose 2 compared to post-dose 1, particularly for systemic AEs. The geometric mean concentrations of anti-SARS-CoV-2-RBD IgG antibody reached 2163·6/2599·2 BAU/mL in GBP510 adjuvanted with AS03 recipients (10 µg/25 µg) by 14 days after the second dose. Two-dose vaccination of 10 µg or 25 µg GBP510 adjuvanted with AS03 induced high titres of neutralizing antibody via pseudovirus (1369·0/1431·5 IU/mL) and wild-type virus (949·8/861·0 IU/mL) assay. Interpretation: GBP510 adjuvanted with AS03 was well tolerated and highly immunogenic. These results support further development of the vaccine candidate, which is currently being evaluated in Phase 3. Funding: This work was supported, in whole or in part, by funding from CEPI and the Bill & Melinda Gates Foundation Investment ID OPP1148601. The Bill & Melinda Gates Foundation supported this project for the generation of IND-enabling data and CEPI supported this clinical study.

Disordered eating and self-harm as risk factors for poorer mental health during the COVID-19 pandemic: a UK-based birth cohort study.

BACKGROUND: Young adults and especially those with pre-existing mental health conditions, such as disordered eating and self-harm, appear to be at greater risk of developing metal health problems during the COVID-19 pandemic. However, it is unclear whether this increased risk is affected by any changes in lockdown restrictions, and whether any lifestyle changes could moderate this increased risk. METHODS: In a longitudinal UK-based birth cohort (The Avon Longitudinal Study of Parents and Children, ALSPAC) we assessed the relationship between pre-pandemic measures of disordered eating and self-harm and mental health during the COVID-19 pandemic in 2657 young adults. Regression models examined the relationship between self-reported disordered eating, self-harm, and both disordered eating and self-harm at age 25 years and depressive symptoms, anxiety symptoms and mental wellbeing during a period of eased restrictions in the COVID-19 pandemic (May-July 2020) when participants were aged 27-29 years. Analyses were adjusted for sex, questionnaire completion date, pre-pandemic socioeconomic disadvantage and pre-pandemic mental health and wellbeing. We also examined whether lifestyle changes (sleep, exercise, alcohol, visiting green space, eating, talking with family/friends, hobbies, relaxation) in the initial UK lockdown (April-May 2020) moderated these associations. RESULTS: Pre-existing disordered eating, self-harm and comorbid disordered eating and self-harm were all associated with the reporting of a higher frequency of depressive symptoms and anxiety symptoms, and poorer mental wellbeing during the pandemic compared to individuals without disordered eating and self-harm. Associations remained when adjusting for pre-pandemic mental health measures. There was little evidence that interactions between disordered eating and self-harm exposures and lifestyle change moderators affected pandemic mental health and wellbeing. CONCLUSIONS: Young adults with pre-pandemic disordered eating, self-harm and comorbid disordered eating and self-harm were at increased risk for developing symptoms of depression, anxiety and poor mental wellbeing during the COVID-19 pandemic, even when accounting for pre-pandemic mental health. Lifestyle changes during the pandemic do not appear to alter this risk. A greater focus on rapid and responsive service provision is essential to reduce the impact of the pandemic on the mental health of these already vulnerable individuals. The aim of this project was to explore the mental health of young adults with disordered eating behaviours (such as fasting, vomiting/taking laxatives, binge-eating and excessive exercise) and self-harm during the COVID-19 pandemic. We analysed data from an established study that has followed children from birth (in 1991 and 1992) up to present day, including during the pandemic when participants were 28 years old. We looked at the relationship between disordered eating and/or self-harm behaviours from before the pandemic and mental health problems (symptoms of depression and anxiety) and mental wellbeing during the pandemic. We also explored whether there were any lifestyle changes (such as changes in sleep, exercise, visiting green space) that might be linked to better mental health and wellbeing in young adults with disordered eating and self-harm. We found that young adults with prior disordered eating and/or self-harm had more symptoms of depression and anxiety, and worse mental wellbeing than individuals without prior disordered eating or self-harm. However, lifestyle changes did not appear to affect mental health and wellbeing in these young adults. Our findings suggest that people with a history of disordered eating and/or self-harm were at high risk for developing mental health problems during the pandemic, and they will need help from mental health services.