rVSVΔG-ZEBOV-GP is the first approved vaccine with clinical efficacy against Ebola virus disease. Although a seroprotective threshold has not been defined for those at occupational risk of exposure, the current vaccine strategy is to attain a sustained high level of antibody titres. The aim of this trial was to explore the effects of delayed boosting upon both the height and duration of antibody titres following primary immunisation. In this open-label phase 2 randomised controlled trial, we compared antibody titres at month 36in participants who had received a homologous booster dose at month 18following primary immunisation with those who had received no booster. From Oct 25, 2016, to Jan 29, 2020, healthy adults aged 18years or older deemed at occupational risk of exposure to Ebola virus due to laboratory work, clinical duties, or travel to an active endemic region were recruited from four hospital clinics in the USA and one hospital clinic in Canada and received primary vaccination with 2×107 plaque-forming unit per mL of VSVΔG-ZEBOV-GP. 18months later, individuals who consented and were still eligible were randomly assigned 1:1 to receive either a homologous booster dose or no booster. Study visits for safety and serial blood collections for antibody titres were done on enrolled participants at months 0, 1, 3, 6, 12, 18, 19, 24, 30, and 36. Through July, 2021, a web-based application was used for randomisation, including assignments with schedules for each of the five sites using mixed permuted blocks. The trial was not masked to participants or site staff. The primary endpoint was a comparison of geometric mean titres (GMTs) of anti-Ebola virus glycoprotein IgG antibody at month 36 (ie, 18months after randomisation) for all randomly assigned participants who completed the 36months of follow-up (primary analysis cohort). Investigators were aware of antibody titres from baseline (enrolment) through month 18but were masked to summary data by randomisation group after month 18. This study is registered with ClinicalTrials.gov (NCT02788227). Of the 248participants who enrolled and received their primary immunisation, 114proceeded to the randomisation step at month 18. The two randomisation groups were balanced: 57participants (24 [42%] of whom were female; median age was 42years [IQR 35-50]) were randomly assigned to the booster group and 57 (24 [42%] of whom were female; median age was 42years [IQR 36-51]) to the no-booster group. Of those randomly assigned, 92participants (45 in the booster group and 47in the no-booster group) completed 36months of follow-up. At 18months after primary immunisation, GMTs in the no-booster group increased from a baseline of 10ELISA units (EU)/mL (95% CI 7-14) to 1451EU/mL (1118-1882); GMTs in the booster group increased from 9EU/mL (6-16) to 1769EU/mL (1348-2321). At month 19, GMTs were 31 408EU/mL (23 181-42 554) for the booster group and 1406EU/mL (1078-1833) for the no-booster group; at month 36, GMTs were 10 146EU/mL (7960-12 933) for the booster group and 1240EU/mL (984-1563) for the no-booster group. Accordingly, the geometric mean ratio (GMR) of antibody titres had increased almost 21-fold more in the booster versus no-booster group at 1month after booster administration (GMR 20·6; 95% CI 18·2-23·0; p<0·0001) and was still over 7-fold higher at month 36 (GMR 7·8; 95% CI 5·5-10·2; p<0·0001). Consistent with previous reports of this vaccine's side-effects, transient mono-articular or oligo-articular arthritis was diagnosed in 18 (9%) of 207primary vaccination recipients; after randomisation, arthritis was diagnosed in one (2%)of 57participants in the no-booster group. No new cases of arthritis developed after booster administration. Four serious adverse events occurred following randomisation: one (epistaxis) in the booster group and three (gastrointestinal haemorrhage, prostate cancer, and tachyarrhythmia) in the no-booster group. None of the serious adverse events was judged attributable to the booster vaccination assignment. In addition to no new safety concerns and in marked contrast to earlier trials evaluating short-term boosting, delaying a rVSVΔG-ZEBOV-GP booster until month 18resulted in an increase in GMT that remained several-fold above the no-booster group GMT for at least 18months. These findings could have implications for defining the optimal timing of booster doses as pre-exposure prophylaxis in populations at ongoing risk for Ebola virus exposure. The Division of Intramural Research and the Division of Clinical Research of the National Institute of Allergyand Infectious Diseases at the US National Institutes of Health, Canadian Immunization Research Network through the Public Health Agency of Canada, Canadian Institutes of Health Research, and the US Defense Threat Reduction Agency.
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Nov 1, 2024
Raden Mas Teja Nursasongka + 5
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