SORA

Advancing, promoting and sharing knowledge of health through excellence in teaching, clinical practice and research into the prevention and treatment of illness

Determinants of antibody persistence across doses and continents after single-dose rVSV-ZEBOV vaccination for Ebola virus disease: an observational cohort study.

Huttner, A; Agnandji, ST; Combescure, C; Fernandes, JF; Bache, EB; Kabwende, L; Ndungu, FM; Brosnahan, J; Monath, TP; Lemaître, B; et al. Huttner, A; Agnandji, ST; Combescure, C; Fernandes, JF; Bache, EB; Kabwende, L; Ndungu, FM; Brosnahan, J; Monath, TP; Lemaître, B; Grillet, S; Botto, M; Engler, O; Portmann, J; Siegrist, D; Bejon, P; Silvera, P; Kremsner, P; Siegrist, C-A; VEBCON; VSV-EBOVAC; VSV-EBOPLUS Consortia (2018) Determinants of antibody persistence across doses and continents after single-dose rVSV-ZEBOV vaccination for Ebola virus disease: an observational cohort study. Lancet Infect Dis, 18 (7). pp. 738-748. ISSN 1474-4457 https://doi.org/10.1016/S1473-3099(18)30165-8
SGUL Authors: Krishna, Sanjeev

[img]
Preview
PDF Accepted Version
Available under License Creative Commons Attribution Non-commercial No Derivatives.

Download (868kB) | Preview

Abstract

BACKGROUND: The recombinant vesicular stomatitis virus (rVSV) vaccine expressing the Zaire Ebola virus (ZEBOV) glycoprotein is efficacious in the weeks following single-dose injection, but duration of immunity is unknown. We aimed to assess antibody persistence at 1 and 2 years in volunteers who received single-dose rVSV-ZEBOV in three previous trials. METHODS: In this observational cohort study, we prospectively followed-up participants from the African and European phase 1 rVSV-ZEBOV trials, who were vaccinated once in 2014-15 with 300 000 (low dose) or 10-50 million (high dose) plaque-forming units (pfu) of rVSV-ZEBOV vaccine to assess ZEBOV glycoprotein (IgG) antibody persistence. The primary outcome was ZEBOV glycoprotein-specific IgG geometric mean concentrations (GMCs) measured yearly by ELISA compared with 1 month (ie, 28 days) after immunisation. We report GMCs up to 2 years (Geneva, Switzerland, including neutralising antibodies up to 6 months) and 1 year (Lambaréné, Gabon; Kilifi, Kenya) after vaccination and factors associated with higher antibody persistence beyond 6 months, according to multivariable analyses. Trials and the observational study were registered at ClinicalTrials.gov (Geneva: NCT02287480 and NCT02933931; Kilifi: NCT02296983) and the Pan-African Clinical Trials Registry (Lambaréné PACTR201411000919191). FINDINGS: Of 217 vaccinees from the original studies (102 from the Geneva study, 75 from the Lambaréné study, and 40 from the Kilifi study), 197 returned and provided samples at 1 year (95 from the Geneva study, 63 from the Lambaréné, and 39 from the Kilifi study) and 90 at 2 years (all from the Geneva study). In the Geneva group, 44 (100%) of 44 participants who had been given a high dose (ie, 10-50 million pfu) of vaccine and who were seropositive at day 28 remained seropositive at 2 years, whereas 33 (89%) of 37 who had been given the low dose (ie, 300 000 pfu) remained seropositive for 2 years (p=0·042). In participants who had received a high dose, ZEBOV glycoprotein IgG GMCs decreased significantly between their peak (at 1-3 months) and month 6 after vaccination in Geneva (p<0·0001) and Lambaréné (p=0·0298) but not in Kilifi (p=0·5833) and subsequently remained stable at all sites apart from Geneva, where GMC in those given a high dose of vaccine increased significantly between 6 months and 1 year (p=0·0264). Antibody persistence was similar at 1 year and at 6 months in those who had received a low dose of vaccine, with lower titres among participants from the Geneva study at 2 years than at 1 year after vaccination (GMC ratio 0·61, 95% CI 0·49-0·77; p<0·0001). In multivariable analyses, predictors of increased IgG GMCs beyond 6 months included high-dose versus low-dose vaccination (Geneva p=0·0133; Lambaréné p=0·008) and vaccine-related arthritis (p=0·0176), but not sex, age, or baseline seropositivity (all p>0·05). Neutralising antibodies seem to be less durable, with seropositivity dropping from 64-71% at 28 days to 27-31% at 6 months in participants from the Geneva study. INTERPRETATION: Antibody responses to single-dose rVSV-ZEBOV vaccination are sustained across dose ranges and settings, a key criterion in countries where booster vaccinations would be impractical. FUNDING: The Wellcome Trust and Innovative Medicines Initiative 2 Joint Undertaking.

Item Type: Article
Additional Information: © 2018. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/
Keywords: Adult, Antibodies, Viral, Cohort Studies, Dose-Response Relationship, Drug, Ebola Vaccines, Ebolavirus, Female, Hemorrhagic Fever, Ebola, Humans, Kenya, Male, Medication Adherence, Middle Aged, Switzerland, VEBCON, VSV-EBOVAC, VSV-EBOPLUS Consortia, Humans, Hemorrhagic Fever, Ebola, Ebola Vaccines, Antibodies, Viral, Cohort Studies, Dose-Response Relationship, Drug, Adult, Middle Aged, Kenya, Switzerland, Female, Male, Ebolavirus, Medication Adherence, Adult, Antibodies, Viral, Cohort Studies, Dose-Response Relationship, Drug, Ebola Vaccines, Ebolavirus, Female, Hemorrhagic Fever, Ebola, Humans, Kenya, Male, Medication Adherence, Middle Aged, Switzerland, 1103 Clinical Sciences, 1108 Medical Microbiology, Microbiology
SGUL Research Institute / Research Centre: Academic Structure > Infection and Immunity Research Institute (INII)
Journal or Publication Title: Lancet Infect Dis
ISSN: 1474-4457
Language: eng
Dates:
DateEvent
July 2018Published
5 April 2018Published Online
14 February 2018Accepted
Publisher License: Creative Commons: Attribution-Noncommercial-No Derivative Works 4.0
Projects:
Project IDFunderFunder ID
203077Wellcome Trusthttp://dx.doi.org/10.13039/100004440
PubMed ID: 29627147
Web of Science ID: WOS:000436794600034
Go to PubMed abstract
URI: https://openaccess.sgul.ac.uk/id/eprint/111741
Publisher's version: https://doi.org/10.1016/S1473-3099(18)30165-8

Actions (login required)

Edit Item Edit Item