Determinants of antibody persistence across doses and continents after single-dose rVSV-ZEBOV vaccination for Ebola virus disease: an observational cohort study
<strong>Background</strong> 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...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Journal article |
| Published: |
Elsevier
2018
|
| _version_ | 1797083225812631552 |
|---|---|
| author | Huttner, A Agnandji, S Combescure, C Fernandes, J Bache, E Kabwende, L Ndungu, F Brosnahan, J Monath, T Lemaître, B Grillet, S Botto, M Engler, O Portmann, J Siegrist, D Bejon, P Silvera, P Kremsner, P Siegrist, C Krishna, S Addo, M Becker, S Krähling, V Njuguna, P Kieny, M Ahmed, R Anderson, J Auderset, F Borgianni, L Ciabattini, A Haks, M Harandi, A Heppner, D Gerlini, A Medaglini, D Ottenhoff, T Pejoski, D Page, M Pozzi, G Santoro, F Dubey, S Fernandes, J Nakaya, H Orourke, F Pozzi, G Rothenberger, S |
| author_facet | Huttner, A Agnandji, S Combescure, C Fernandes, J Bache, E Kabwende, L Ndungu, F Brosnahan, J Monath, T Lemaître, B Grillet, S Botto, M Engler, O Portmann, J Siegrist, D Bejon, P Silvera, P Kremsner, P Siegrist, C Krishna, S Addo, M Becker, S Krähling, V Njuguna, P Kieny, M Ahmed, R Anderson, J Auderset, F Borgianni, L Ciabattini, A Haks, M Harandi, A Heppner, D Gerlini, A Medaglini, D Ottenhoff, T Pejoski, D Page, M Pozzi, G Santoro, F Dubey, S Fernandes, J Nakaya, H Orourke, F Pozzi, G Rothenberger, S |
| author_sort | Huttner, A |
| collection | OXFORD |
| description | <strong>Background</strong> 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. <strong>Methods</strong> 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). <strong>Findings</strong> 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. <strong>Interpretation</strong> 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. |
| first_indexed | 2024-03-07T01:38:42Z |
| format | Journal article |
| id | oxford-uuid:9617ec77-41bd-40aa-9288-d3eeb9223b61 |
| institution | University of Oxford |
| last_indexed | 2024-03-07T01:38:42Z |
| publishDate | 2018 |
| publisher | Elsevier |
| record_format | dspace |
| spelling | oxford-uuid:9617ec77-41bd-40aa-9288-d3eeb9223b612022-03-26T23:50:51ZDeterminants of antibody persistence across doses and continents after single-dose rVSV-ZEBOV vaccination for Ebola virus disease: an observational cohort studyJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:9617ec77-41bd-40aa-9288-d3eeb9223b61Symplectic Elements at OxfordElsevier2018Huttner, AAgnandji, SCombescure, CFernandes, JBache, EKabwende, LNdungu, FBrosnahan, JMonath, TLemaître, BGrillet, SBotto, MEngler, OPortmann, JSiegrist, DBejon, PSilvera, PKremsner, PSiegrist, CKrishna, SAddo, MBecker, SKrähling, VNjuguna, PKieny, MAhmed, RAnderson, JAuderset, FBorgianni, LCiabattini, AHaks, MHarandi, AHeppner, DGerlini, AMedaglini, DOttenhoff, TPejoski, DPage, MPozzi, GSantoro, FDubey, SFernandes, JNakaya, HOrourke, FPozzi, GRothenberger, S<strong>Background</strong> 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. <strong>Methods</strong> 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). <strong>Findings</strong> 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. <strong>Interpretation</strong> 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. |
| spellingShingle | Huttner, A Agnandji, S Combescure, C Fernandes, J Bache, E Kabwende, L Ndungu, F Brosnahan, J Monath, T Lemaître, B Grillet, S Botto, M Engler, O Portmann, J Siegrist, D Bejon, P Silvera, P Kremsner, P Siegrist, C Krishna, S Addo, M Becker, S Krähling, V Njuguna, P Kieny, M Ahmed, R Anderson, J Auderset, F Borgianni, L Ciabattini, A Haks, M Harandi, A Heppner, D Gerlini, A Medaglini, D Ottenhoff, T Pejoski, D Page, M Pozzi, G Santoro, F Dubey, S Fernandes, J Nakaya, H Orourke, F Pozzi, G Rothenberger, S Determinants of antibody persistence across doses and continents after single-dose rVSV-ZEBOV vaccination for Ebola virus disease: an observational cohort study |
| title | Determinants of antibody persistence across doses and continents after single-dose rVSV-ZEBOV vaccination for Ebola virus disease: an observational cohort study |
| title_full | Determinants of antibody persistence across doses and continents after single-dose rVSV-ZEBOV vaccination for Ebola virus disease: an observational cohort study |
| title_fullStr | Determinants of antibody persistence across doses and continents after single-dose rVSV-ZEBOV vaccination for Ebola virus disease: an observational cohort study |
| title_full_unstemmed | Determinants of antibody persistence across doses and continents after single-dose rVSV-ZEBOV vaccination for Ebola virus disease: an observational cohort study |
| title_short | Determinants of antibody persistence across doses and continents after single-dose rVSV-ZEBOV vaccination for Ebola virus disease: an observational cohort study |
| title_sort | determinants of antibody persistence across doses and continents after single dose rvsv zebov vaccination for ebola virus disease an observational cohort study |
| work_keys_str_mv | AT huttnera determinantsofantibodypersistenceacrossdosesandcontinentsaftersingledoservsvzebovvaccinationforebolavirusdiseaseanobservationalcohortstudy AT agnandjis determinantsofantibodypersistenceacrossdosesandcontinentsaftersingledoservsvzebovvaccinationforebolavirusdiseaseanobservationalcohortstudy AT combescurec determinantsofantibodypersistenceacrossdosesandcontinentsaftersingledoservsvzebovvaccinationforebolavirusdiseaseanobservationalcohortstudy AT fernandesj determinantsofantibodypersistenceacrossdosesandcontinentsaftersingledoservsvzebovvaccinationforebolavirusdiseaseanobservationalcohortstudy AT bachee determinantsofantibodypersistenceacrossdosesandcontinentsaftersingledoservsvzebovvaccinationforebolavirusdiseaseanobservationalcohortstudy AT kabwendel determinantsofantibodypersistenceacrossdosesandcontinentsaftersingledoservsvzebovvaccinationforebolavirusdiseaseanobservationalcohortstudy AT ndunguf determinantsofantibodypersistenceacrossdosesandcontinentsaftersingledoservsvzebovvaccinationforebolavirusdiseaseanobservationalcohortstudy AT brosnahanj determinantsofantibodypersistenceacrossdosesandcontinentsaftersingledoservsvzebovvaccinationforebolavirusdiseaseanobservationalcohortstudy AT monatht determinantsofantibodypersistenceacrossdosesandcontinentsaftersingledoservsvzebovvaccinationforebolavirusdiseaseanobservationalcohortstudy AT lemaitreb determinantsofantibodypersistenceacrossdosesandcontinentsaftersingledoservsvzebovvaccinationforebolavirusdiseaseanobservationalcohortstudy AT grillets determinantsofantibodypersistenceacrossdosesandcontinentsaftersingledoservsvzebovvaccinationforebolavirusdiseaseanobservationalcohortstudy AT bottom determinantsofantibodypersistenceacrossdosesandcontinentsaftersingledoservsvzebovvaccinationforebolavirusdiseaseanobservationalcohortstudy AT englero determinantsofantibodypersistenceacrossdosesandcontinentsaftersingledoservsvzebovvaccinationforebolavirusdiseaseanobservationalcohortstudy AT portmannj determinantsofantibodypersistenceacrossdosesandcontinentsaftersingledoservsvzebovvaccinationforebolavirusdiseaseanobservationalcohortstudy AT siegristd determinantsofantibodypersistenceacrossdosesandcontinentsaftersingledoservsvzebovvaccinationforebolavirusdiseaseanobservationalcohortstudy AT bejonp determinantsofantibodypersistenceacrossdosesandcontinentsaftersingledoservsvzebovvaccinationforebolavirusdiseaseanobservationalcohortstudy AT silverap determinantsofantibodypersistenceacrossdosesandcontinentsaftersingledoservsvzebovvaccinationforebolavirusdiseaseanobservationalcohortstudy AT kremsnerp determinantsofantibodypersistenceacrossdosesandcontinentsaftersingledoservsvzebovvaccinationforebolavirusdiseaseanobservationalcohortstudy AT siegristc determinantsofantibodypersistenceacrossdosesandcontinentsaftersingledoservsvzebovvaccinationforebolavirusdiseaseanobservationalcohortstudy AT krishnas determinantsofantibodypersistenceacrossdosesandcontinentsaftersingledoservsvzebovvaccinationforebolavirusdiseaseanobservationalcohortstudy AT addom determinantsofantibodypersistenceacrossdosesandcontinentsaftersingledoservsvzebovvaccinationforebolavirusdiseaseanobservationalcohortstudy AT beckers determinantsofantibodypersistenceacrossdosesandcontinentsaftersingledoservsvzebovvaccinationforebolavirusdiseaseanobservationalcohortstudy AT krahlingv determinantsofantibodypersistenceacrossdosesandcontinentsaftersingledoservsvzebovvaccinationforebolavirusdiseaseanobservationalcohortstudy AT njugunap determinantsofantibodypersistenceacrossdosesandcontinentsaftersingledoservsvzebovvaccinationforebolavirusdiseaseanobservationalcohortstudy AT kienym determinantsofantibodypersistenceacrossdosesandcontinentsaftersingledoservsvzebovvaccinationforebolavirusdiseaseanobservationalcohortstudy AT ahmedr determinantsofantibodypersistenceacrossdosesandcontinentsaftersingledoservsvzebovvaccinationforebolavirusdiseaseanobservationalcohortstudy AT andersonj determinantsofantibodypersistenceacrossdosesandcontinentsaftersingledoservsvzebovvaccinationforebolavirusdiseaseanobservationalcohortstudy AT audersetf determinantsofantibodypersistenceacrossdosesandcontinentsaftersingledoservsvzebovvaccinationforebolavirusdiseaseanobservationalcohortstudy AT borgiannil determinantsofantibodypersistenceacrossdosesandcontinentsaftersingledoservsvzebovvaccinationforebolavirusdiseaseanobservationalcohortstudy AT ciabattinia determinantsofantibodypersistenceacrossdosesandcontinentsaftersingledoservsvzebovvaccinationforebolavirusdiseaseanobservationalcohortstudy AT haksm determinantsofantibodypersistenceacrossdosesandcontinentsaftersingledoservsvzebovvaccinationforebolavirusdiseaseanobservationalcohortstudy AT harandia determinantsofantibodypersistenceacrossdosesandcontinentsaftersingledoservsvzebovvaccinationforebolavirusdiseaseanobservationalcohortstudy AT heppnerd determinantsofantibodypersistenceacrossdosesandcontinentsaftersingledoservsvzebovvaccinationforebolavirusdiseaseanobservationalcohortstudy AT gerlinia determinantsofantibodypersistenceacrossdosesandcontinentsaftersingledoservsvzebovvaccinationforebolavirusdiseaseanobservationalcohortstudy AT medaglinid determinantsofantibodypersistenceacrossdosesandcontinentsaftersingledoservsvzebovvaccinationforebolavirusdiseaseanobservationalcohortstudy AT ottenhofft determinantsofantibodypersistenceacrossdosesandcontinentsaftersingledoservsvzebovvaccinationforebolavirusdiseaseanobservationalcohortstudy AT pejoskid determinantsofantibodypersistenceacrossdosesandcontinentsaftersingledoservsvzebovvaccinationforebolavirusdiseaseanobservationalcohortstudy AT pagem determinantsofantibodypersistenceacrossdosesandcontinentsaftersingledoservsvzebovvaccinationforebolavirusdiseaseanobservationalcohortstudy AT pozzig determinantsofantibodypersistenceacrossdosesandcontinentsaftersingledoservsvzebovvaccinationforebolavirusdiseaseanobservationalcohortstudy AT santorof determinantsofantibodypersistenceacrossdosesandcontinentsaftersingledoservsvzebovvaccinationforebolavirusdiseaseanobservationalcohortstudy AT dubeys determinantsofantibodypersistenceacrossdosesandcontinentsaftersingledoservsvzebovvaccinationforebolavirusdiseaseanobservationalcohortstudy AT fernandesj determinantsofantibodypersistenceacrossdosesandcontinentsaftersingledoservsvzebovvaccinationforebolavirusdiseaseanobservationalcohortstudy AT nakayah determinantsofantibodypersistenceacrossdosesandcontinentsaftersingledoservsvzebovvaccinationforebolavirusdiseaseanobservationalcohortstudy AT orourkef determinantsofantibodypersistenceacrossdosesandcontinentsaftersingledoservsvzebovvaccinationforebolavirusdiseaseanobservationalcohortstudy AT pozzig determinantsofantibodypersistenceacrossdosesandcontinentsaftersingledoservsvzebovvaccinationforebolavirusdiseaseanobservationalcohortstudy AT rothenbergers determinantsofantibodypersistenceacrossdosesandcontinentsaftersingledoservsvzebovvaccinationforebolavirusdiseaseanobservationalcohortstudy |