TY - JOUR
T1 - Safety and Immunogenicity of Accelerated Heterologous Two-dose Ebola Vaccine Regimens in Adults With and Without HIV in Africa
AU - Mwesigwa, Betty
AU - Sawe, Fredrick
AU - Oyieko, Janet
AU - Mwakisisile, Joel
AU - Viegas, Edna
AU - Akintunde, Gideon Akindiran
AU - Kosgei, Josphat
AU - Kokogho, Afoke
AU - Ntinginya, Nyanda
AU - Jani, Ilesh
AU - Shukarev, Georgi
AU - Hooper, Jay W
AU - Kwilas, Steven A
AU - Ward, Lucy A
AU - Rusnak, Janice
AU - Bounds, Callie
AU - Overman, Rachel
AU - Badorrek, Christopher S
AU - Eller, Leigh Anne
AU - Eller, Michael A
AU - Polyak, Christina S
AU - Moodley, Amber
AU - Tran, Chi L
AU - Costanzo, Margaret C
AU - Leggat, David J
AU - Paquin-Proulx, Dominic
AU - Naluyima, Prossy
AU - Nkafu Anumendem, Dickson
AU - Gaddah, Auguste
AU - Luhn, Kerstin
AU - Hendriks, Jenny
AU - McLean, Chelsea
AU - Douoguih, Macaya
AU - Kibuuka, Hannah
AU - Robb, Merlin L
AU - Robinson, Cynthia
AU - Ake, Julie A
N1 - Published by Oxford University Press on behalf of Infectious Diseases Society of America 2024.
PY - 2024/4/24
Y1 - 2024/4/24
N2 - BACKGROUND: Shorter prophylactic vaccine schedules may offer more rapid protection against Ebola in resource-limited settings.METHODS: This randomized, observer-blind, placebo-controlled, phase 2 trial conducted in five sub-Saharan African countries included people without HIV (PWOH, n = 249) and people living with HIV (PLWH, n = 250). Adult participants received one of two accelerated Ebola vaccine regimens (MVA-BN-Filo, Ad26.ZEBOV administered 14 days apart [n = 79] or Ad26.ZEBOV, MVA-BN-Filo administered 28 days apart [n = 322]) or saline/placebo (n = 98). The primary endpoints were safety (adverse events [AEs]) and immunogenicity (Ebola virus [EBOV] glycoprotein-specific binding antibody responses). Binding antibody responders were defined as participants with a > 2.5-fold increase from baseline or the lower limit of quantification if negative at baseline.RESULTS: The mean age was 33.4 years, 52% of participants were female, and among PLWH, the median (interquartile range) CD4+ cell count was 560.0 (418.0-752.0) cells/μL. AEs were generally mild/moderate with no vaccine-related serious AEs or remarkable safety profile differences by HIV status. At 21 days post-dose 2, EBOV glycoprotein-specific binding antibody response rates in vaccine recipients were 99% for the 14-day regimen (geometric mean concentrations [GMCs]: 5168 enzyme-linked immunosorbent assay units (EU)/mL in PWOH; 2509 EU/mL in PLWH), and 98% for the 28-day regimen (GMCs: 6037 EU/mL in PWOH; 2939 EU/mL in PLWH). At 12 months post-dose 2, GMCs in PWOH and PLWH were 635 and 514 EU/mL, respectively, for the 14-day regimen and 331 and 360 EU/mL, respectively, for the 28-day regimen.CONCLUSIONS: Accelerated 14- and 28-day Ebola vaccine regimens were safe and immunogenic in PWOH and PLWH in Africa.TRIAL REGISTRATION: NCT02598388.
AB - BACKGROUND: Shorter prophylactic vaccine schedules may offer more rapid protection against Ebola in resource-limited settings.METHODS: This randomized, observer-blind, placebo-controlled, phase 2 trial conducted in five sub-Saharan African countries included people without HIV (PWOH, n = 249) and people living with HIV (PLWH, n = 250). Adult participants received one of two accelerated Ebola vaccine regimens (MVA-BN-Filo, Ad26.ZEBOV administered 14 days apart [n = 79] or Ad26.ZEBOV, MVA-BN-Filo administered 28 days apart [n = 322]) or saline/placebo (n = 98). The primary endpoints were safety (adverse events [AEs]) and immunogenicity (Ebola virus [EBOV] glycoprotein-specific binding antibody responses). Binding antibody responders were defined as participants with a > 2.5-fold increase from baseline or the lower limit of quantification if negative at baseline.RESULTS: The mean age was 33.4 years, 52% of participants were female, and among PLWH, the median (interquartile range) CD4+ cell count was 560.0 (418.0-752.0) cells/μL. AEs were generally mild/moderate with no vaccine-related serious AEs or remarkable safety profile differences by HIV status. At 21 days post-dose 2, EBOV glycoprotein-specific binding antibody response rates in vaccine recipients were 99% for the 14-day regimen (geometric mean concentrations [GMCs]: 5168 enzyme-linked immunosorbent assay units (EU)/mL in PWOH; 2509 EU/mL in PLWH), and 98% for the 28-day regimen (GMCs: 6037 EU/mL in PWOH; 2939 EU/mL in PLWH). At 12 months post-dose 2, GMCs in PWOH and PLWH were 635 and 514 EU/mL, respectively, for the 14-day regimen and 331 and 360 EU/mL, respectively, for the 28-day regimen.CONCLUSIONS: Accelerated 14- and 28-day Ebola vaccine regimens were safe and immunogenic in PWOH and PLWH in Africa.TRIAL REGISTRATION: NCT02598388.
U2 - 10.1093/cid/ciae215
DO - 10.1093/cid/ciae215
M3 - Article
C2 - 38657084
SN - 1058-4838
JO - Clinical Infectious Diseases
JF - Clinical Infectious Diseases
ER -