rVSVΔG-ZEBOV-GP induces over 40-fold increase in GP-ELISA antibody response in HIV patientsTrial shows vaccine triggers strong response in people with HIV

BACKGROUND: A single dose of the replication-competent rVSVΔG-ZEBOV-GP vaccine is recommended by the WHO Strategic Advisory Group of Experts on Immunization during Ebola virus disease outbreaks. We aimed to assess the immunogenicity, safety, and tolerability of this vaccine in adults and adolescents with HIV. METHODS: In this phase 2, multicentre, double-blind, randomised, placebo-controlled trial, we enrolled participants aged 13-70 years who had laboratory-confirmed HIV infection, were on antiretroviral therapy (ART), had an undetectable viral load (<40 copies per mL), and had a CD4 count of 200 cells per μL or more at four ambulatory settings in Montreal and Ottawa (Canada), Dakar (Senegal), and Bobo-Dioulasso (Burkina Faso). Sequential enrolment of five study cohorts occurred over time at each study site according to CD4 counts: cohort 1 (adults [age 18-70 years] with a CD4 count ≥500 cells per μL), cohort 2 (adults with a CD4 count of >350 and <500 cells per μL), cohort 3 (adults with a CD4 count of 200-350 cells per μL), cohort 4 (adolescents [age 13-17 years] with a CD4 count ≥200 cells per μL), and cohort 5 (adults and adolescents with a CD4 count ≥200 cells per μL). Participants were randomly assigned 4:1 to receive one dose (cohorts 1-4) or two doses (56 days apart; cohort 5) of rVSVΔG-ZEBOV-GP or placebo, administered at day 0. An unmasked staff member at each site prepared the vaccine or placebo; all other study personnel and participants were masked to group assignments. Participants were followed up to day 365. The primary immunogenicity endpoints, assessed in the per-protocol population, were Ebola virus-specific antibody responses measured by glycoprotein ELISA (GP-ELISA; geometric mean titre ratio [GMTR]) and neutralisation (geometric mean fold increase [GMFI] of plaque reduction neutralisation test [PRNT]) on day 28 in cohorts 1-5 combined (combined cohort), and 28 days after the second dose of vaccine or placebo in cohort 5. The primary safety endpoints, assessed in the as-treated population, were: the occurrence of each solicited local and systemic adverse event during a 14-day follow-up period after each vaccination; fever, joint pain (arthralgia), joint swelling (arthritis), rash, and blisters or vesicular lesions during a 42-day follow-up period after vaccination; any haematological and biochemical laboratory abnormality at 0, 3, 7, 14, and 28 days after each vaccine; occurrence of any unsolicited adverse event during a 42-day follow-up period after each vaccination; and occurrence of vaccine-related serious adverse events up to day 365 of the study. The trial is registered at ClinicalTrials.gov (NCT03031912) and is complete. FINDINGS: Between Aug 1, 2017, and March 3, 2022, we assessed 647 individuals for eligibility, 251 of whom were enrolled. 120 (48%) participants were male, 130 (52%) were female, 225 (90%) were Black (Black African or African Canadian), and median age was 52·0 years (IQR 48·0-56·0). 51 participants were enrolled in cohort 1, 50 in cohort 2, 50 in cohort 3, 50 in cohort 4, and 50 in cohort 5. 202 (80%) participants were assigned to receive rVSVΔG-ZEBOV-GP and 49 (20%) were assigned to receive placebo. One dose of rVSVΔG-ZEBOV-GP elicited superior immune responses compared with placebo, with GP-ELISA antibodies in the combined cohort (per-protocol population) increasing over 40-fold (GMTR 42·90, 95% CI 31·49-58·43; p<0·0001). In cohort 5, the GP-ELISA geometric mean titre 28 days after the second dose was over 200-fold higher in the rVSV-ZEBOV-GP group than in the placebo group (GMTR 208·66, 95% CI 115·57-376·72; p<0·0001). GFMI of PRNT titres was 11·51 (95% CI 9·82-13·50) at day 28 for participants in the combined cohort who received one dose of rVSVΔG-ZEBOV-GP and 86·64 (95% CI 69·85-107·46) 28 days after a second dose in cohort 5. Solicited adverse events up to 42 days after vaccination were mild to moderate in severity and transient. In the 14 days after the first dose of vaccine, the most common adverse events were injection site pain (130 of 201 participants, 65%), headache (109 of 201, 54%), fatigue (91 of 201, 45%), and joint pain (50 of 201, 25%). Unsolicited adverse events to day 42 were not different between participants who received rVSVΔG-ZEBOV-GP (103 of 201, 51%) and those who received placebo (22 of 49, 45%; p=0·52). No clinically significant changes in CD4 cell counts, HIV viral load, or haematological and biochemical laboratory tests were observed. INTERPRETATION: A single dose of rVSVΔG-ZEBOV-GP is highly immunogenic in people living with HIV on ART with an undetectable viral load, with a tolerable safety profile. A two-dose regimen in a subset of participating adolescents and adults showed a significant boosting at day 28, with no increase in reactogenicity compared with the first dose. FUNDING: International Development Research Centre, US Department of Health and Human Services, Administration for Strategic Preparedness and Response, Biomedical Advanced Research and Development Authority, and the Coalition for Epidemic Preparedness. TRANSLATION: For the French translation of the abstract see Supplementary Materials section.