ABSTRACT
This study aimed to investigate the efficacy of different COVID-19 booster vaccines by measuring the serum antibody titer. SARS-CoV-2 anti-nucleocapsid protein antibody (N-Ab), anti-spike protein antibody (S-Ab), and neutralizing antibody (Neut.Ab) were measured before and 4-6 weeks after booster vaccinations in healthcare personnel with a previous vaccination within 3-6 months. Personnel who previously received two doses of ChAdOx1 vaccine or two doses of BNT162b2 vaccine received the BNT162b2 vaccine (AAP and PPP groups, respectively). Personnel who previously received two doses of mRNA-1273 received the same vaccine as a booster dose (MMM group). Of the 917 participants, the AAP, MMM, and PPP groups comprised 837 (91.3%), 27 (2.9%), and 53 (5.8%) participants, respectively. The pre-booster S-Ab and Neut.Ab titer were significantly lower in the AAP group. After the booster vaccination, all participants were positive for S-Ab and Neut.Ab; furthermore, the S-Ab and Neut.Ab titer significantly increased in all three groups, although the post-booster S-Ab was lower in the AAP group than in the other groups. The post-booster Neut.Ab titer showed no significant difference among the groups. Our study's results suggest that booster vaccination, after two prior vaccinations, shows a significant effect regardless of the type of vaccine administered.
ABSTRACT
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.
ABSTRACT
The coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 can lead to acute respiratory distress syndrome. Awake venovenous extracorporeal membrane oxygenation is known to be effective in patients with critical COVID-19 and respiratory failure. This report describes the rehabilitation course and functional progress of a 63-year-old man who contracted severe COVID-19 and underwent awake venovenous extracorporeal membrane oxygenation. He started rehabilitation from the time of isolation while receiving venovenous extracorporeal membrane oxygenation and underwent a 30-day course of inpatient comprehensive rehabilitation. He regained functional independence and cognitive abilities and was able to walk without assistance at hospital discharge without any complications. This study demonstrates the feasibility of starting rehabilitation for COVID-19 early while the patient is on awake venovenous extracorporeal membrane oxygenation and eventually achieving a favorable outcome.