The Lancet. Infectious diseases · 2026
Safety and immunogenicity of an adenoviral-vectored vaccine against Crimean-Congo haemorrhagic fever in the UK (CCHF01): an open-label, first-in-human, non-randomised, phase 1 clinical trial.
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Pollock Katrina M, Saunders Jack E, Fowler Jamie, Camara Susana, Kakai Ilona, Eordogh Agnes, Plested Gareth, Green Catherine M, da Silva Carla Ferreira, de Whalley Philip, Islam Mohammod K, Marchevsky Natalie G, Belij-Rammerstorfer Sandra, Lambe Teresa, CCHF01 Study Team
Аннотация
BACKGROUND: There are no approved vaccines for Crimean-Congo haemorrhagic fever virus (CCHFV), which remains a WHO priority pathogen for vaccine development. We evaluated the safety and immunogenicity of ChAdOx2 Crimean-Congo haemorrhagic fever (CCHF), a novel, non-replicating adenoviral-vectored vaccine, in a first-in-human phase 1 clinical trial.
METHODS: CCHF01 was an open-label, first-in-human, non-randomised, phase 1 trial conducted at a single centre, the University of Oxford Centre for Clinical Vaccinology and Tropical Medicine in Oxford, UK. Healthy adults aged 18-55 years, with no confirmed or suspected previous CCHFV infection and no known clinically significant medical comorbidities, received two intramuscular doses of ChAdOx2 CCHF administered 12 weeks apart. Six participants were enrolled into a lead-in cohort (cohort 1). 40 participants were enrolled in cohort 2 and stratified by previous vaccination with a ChAdOx-vectored vaccine: cohort 2A (ChAdOx exposed; n=20) and cohort 2B (ChAdOx naive; n=20). Primary outcomes were safety and tolerability, assessed in all participants who received at least one vaccine dose. Secondary outcome was CCHFV glycoprotein-specific binding antibody responses, assessed at prespecified timepoints in participants who received two vaccine doses with available data. The trial was registered on the ISRCTN registry (ISRCTN12 351 734) and is now complete.
FINDINGS: Between Aug 31, 2023, and Jan 31, 2024, 46 adult participants aged 18-55 years were enrolled. Of these, 44 received the second vaccine dose; two were discontinued from further vaccination: one due to persistent neutropenia and one following a mild self-limiting allergic reaction after the first vaccination. Solicited local adverse events occurred in 30 (65%) of 46 participants after the first vaccination and 30 (68%) of 44 after the second vaccination, and solicited systemic adverse events occurred in 39 (85%) of 46 participants after the first vaccination and 28 (64%) of 44 participants after the second vaccination. Reactogenicity was predominantly mild, with injection-site pain and fatigue being the most commonly reported local and systemic adverse events. No serious adverse events were reported. Median CCHFV glycoprotein Gc-specific IgG response was 26·17 arbitrary units (AU) 28 days after first vaccination and was 88·20 AU 28 days after second vaccination. Median GP38-specific IgG response was 92·74 AU 28 days after first vaccination and 1064·13 AU 28 days after second vaccination.
INTERPRETATION: ChAdOx2 CCHF demonstrated acceptable tolerability and induced CCHFV-specific humoral immune responses in this phase 1 trial. These findings provide proof of principle for vaccination against CCHFV and support further clinical development of this vaccine. The effect of previous ChAdOx-vectored vaccination on immunogenicity could not be conclusively determined because of the study sample size and age differences between groups.
FUNDING: UK Research and Innovation.
METHODS: CCHF01 was an open-label, first-in-human, non-randomised, phase 1 trial conducted at a single centre, the University of Oxford Centre for Clinical Vaccinology and Tropical Medicine in Oxford, UK. Healthy adults aged 18-55 years, with no confirmed or suspected previous CCHFV infection and no known clinically significant medical comorbidities, received two intramuscular doses of ChAdOx2 CCHF administered 12 weeks apart. Six participants were enrolled into a lead-in cohort (cohort 1). 40 participants were enrolled in cohort 2 and stratified by previous vaccination with a ChAdOx-vectored vaccine: cohort 2A (ChAdOx exposed; n=20) and cohort 2B (ChAdOx naive; n=20). Primary outcomes were safety and tolerability, assessed in all participants who received at least one vaccine dose. Secondary outcome was CCHFV glycoprotein-specific binding antibody responses, assessed at prespecified timepoints in participants who received two vaccine doses with available data. The trial was registered on the ISRCTN registry (ISRCTN12 351 734) and is now complete.
FINDINGS: Between Aug 31, 2023, and Jan 31, 2024, 46 adult participants aged 18-55 years were enrolled. Of these, 44 received the second vaccine dose; two were discontinued from further vaccination: one due to persistent neutropenia and one following a mild self-limiting allergic reaction after the first vaccination. Solicited local adverse events occurred in 30 (65%) of 46 participants after the first vaccination and 30 (68%) of 44 after the second vaccination, and solicited systemic adverse events occurred in 39 (85%) of 46 participants after the first vaccination and 28 (64%) of 44 participants after the second vaccination. Reactogenicity was predominantly mild, with injection-site pain and fatigue being the most commonly reported local and systemic adverse events. No serious adverse events were reported. Median CCHFV glycoprotein Gc-specific IgG response was 26·17 arbitrary units (AU) 28 days after first vaccination and was 88·20 AU 28 days after second vaccination. Median GP38-specific IgG response was 92·74 AU 28 days after first vaccination and 1064·13 AU 28 days after second vaccination.
INTERPRETATION: ChAdOx2 CCHF demonstrated acceptable tolerability and induced CCHFV-specific humoral immune responses in this phase 1 trial. These findings provide proof of principle for vaccination against CCHFV and support further clinical development of this vaccine. The effect of previous ChAdOx-vectored vaccination on immunogenicity could not be conclusively determined because of the study sample size and age differences between groups.
FUNDING: UK Research and Innovation.