Antibody responses to recombinant vesicular stomatitis virus-Zaire Ebolavirus vaccination for Ebola virus disease across doses and continents
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Antibody responses to recombinant vesicular stomatitis virus-Zaire Ebolavirus vaccination for Ebola virus disease across doses and continents : 5-year durability. / Huttner, Angela; Agnandji, Selidji Todagbe; Engler, Olivier; Hooper, Jay W; Kwilas, Steve; Ricks, Keersten; Clements, Tamara L; Jonsdottir, Hulda R; Nakka, Sravya Sowdamini; Rothenberger, Sylvia; Kremsner, Peter; Züst, Roland; Medaglini, Donata; Ottenhoff, Tom; Harandi, Ali M; Siegrist, Claire-Anne; VEBCON; VSV-EBOVAC Consortium; VSV-EBOPLUS Consortium.
In: CLIN MICROBIOL INFEC, Vol. 29, No. 12, 12.2023, p. 1587-1594.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Antibody responses to recombinant vesicular stomatitis virus-Zaire Ebolavirus vaccination for Ebola virus disease across doses and continents
T2 - 5-year durability
AU - Huttner, Angela
AU - Agnandji, Selidji Todagbe
AU - Engler, Olivier
AU - Hooper, Jay W
AU - Kwilas, Steve
AU - Ricks, Keersten
AU - Clements, Tamara L
AU - Jonsdottir, Hulda R
AU - Nakka, Sravya Sowdamini
AU - Rothenberger, Sylvia
AU - Kremsner, Peter
AU - Züst, Roland
AU - Medaglini, Donata
AU - Ottenhoff, Tom
AU - Harandi, Ali M
AU - Siegrist, Claire-Anne
AU - VEBCON
AU - Addo, Marylyn Martina
AU - VSV-EBOVAC Consortium
AU - VSV-EBOPLUS Consortium
N1 - Copyright © 2023 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.
PY - 2023/12
Y1 - 2023/12
N2 - OBJECTIVES: To report 5-year persistence and avidity of antibodies produced by the live-attenuated recombinant vesicular stomatitis virus (rVSV) expressing the Zaire Ebolavirus (ZEBOV) glycoprotein (GP), known as rVSV-ZEBOV (Ervebo®).METHODS: Healthy adults vaccinated with 300,000 or 10-50 million plaque-forming units of rVSV-ZEBOV in the WHO-coordinated trials of 2014-2015 were followed for up to 4 (Lambaréné, Gabon) and 5 (Geneva, Switzerland) years. We report seropositivity rates, geometric mean titres (GMTs), and population distribution of ZEBOV-GP ELISA IgG antibodies, neutralizing antibodies (pseudovirus and live-virus neutralization) and antibody avidity; the primary outcome was ZEBOV-GP ELISA IgG GMTs at 4 or 5 years compared with 1 year (Y1) after immunization.RESULTS: Among the 168 eligible vaccinees (Geneva: 97 and Lambaréné: 71) enrolled 1 year post-immunization, 146 (87%) remained enrolled at 4 years (Geneva: n = 88, Lambaréné: n = 58), and 84 (87%, Geneva) at 5 years post-vaccination. ZEBOV-GP ELISA IgG GMTs plateaued, with no declining trend from 1 year through the last time point assessed (1147.8 [95% CI 874.3-1507.0] at Y1 versus 1548.1 [95% CI 1136.6-2108.5] at Y5 in Geneva volunteers receiving ≥10 million plaque-forming units of rVSV-ZEBOV), their avidity matching that of ZEBOV convalescents. Live-virus neutralizing antibodies were detected for shorter periods and in fewer vaccinees (53/95 [56%] at Y1 versus 35/84 [42%] at Y5 in Geneva volunteers, all dose levels).DISCUSSION: Titres at Y1 emerged as a correlate of antibody persistence at Y5. The findings of persistent ZEBOV-GP ELISA IgG titres yet shorter-lasting, lower titres of live-virus neutralizing antibodies suggest the contribution of antibody-mediated protective mechanisms other than neutralization. Long-term clinical efficacy of rVSV-ZEBOV, however, requires further study.
AB - OBJECTIVES: To report 5-year persistence and avidity of antibodies produced by the live-attenuated recombinant vesicular stomatitis virus (rVSV) expressing the Zaire Ebolavirus (ZEBOV) glycoprotein (GP), known as rVSV-ZEBOV (Ervebo®).METHODS: Healthy adults vaccinated with 300,000 or 10-50 million plaque-forming units of rVSV-ZEBOV in the WHO-coordinated trials of 2014-2015 were followed for up to 4 (Lambaréné, Gabon) and 5 (Geneva, Switzerland) years. We report seropositivity rates, geometric mean titres (GMTs), and population distribution of ZEBOV-GP ELISA IgG antibodies, neutralizing antibodies (pseudovirus and live-virus neutralization) and antibody avidity; the primary outcome was ZEBOV-GP ELISA IgG GMTs at 4 or 5 years compared with 1 year (Y1) after immunization.RESULTS: Among the 168 eligible vaccinees (Geneva: 97 and Lambaréné: 71) enrolled 1 year post-immunization, 146 (87%) remained enrolled at 4 years (Geneva: n = 88, Lambaréné: n = 58), and 84 (87%, Geneva) at 5 years post-vaccination. ZEBOV-GP ELISA IgG GMTs plateaued, with no declining trend from 1 year through the last time point assessed (1147.8 [95% CI 874.3-1507.0] at Y1 versus 1548.1 [95% CI 1136.6-2108.5] at Y5 in Geneva volunteers receiving ≥10 million plaque-forming units of rVSV-ZEBOV), their avidity matching that of ZEBOV convalescents. Live-virus neutralizing antibodies were detected for shorter periods and in fewer vaccinees (53/95 [56%] at Y1 versus 35/84 [42%] at Y5 in Geneva volunteers, all dose levels).DISCUSSION: Titres at Y1 emerged as a correlate of antibody persistence at Y5. The findings of persistent ZEBOV-GP ELISA IgG titres yet shorter-lasting, lower titres of live-virus neutralizing antibodies suggest the contribution of antibody-mediated protective mechanisms other than neutralization. Long-term clinical efficacy of rVSV-ZEBOV, however, requires further study.
KW - Adult
KW - Animals
KW - Humans
KW - Hemorrhagic Fever, Ebola
KW - Ebolavirus/genetics
KW - Antibody Formation
KW - Democratic Republic of the Congo
KW - Ebola Vaccines
KW - Vesicular Stomatitis
KW - Antibodies, Viral
KW - Vaccination
KW - Antibodies, Neutralizing
KW - Immunoglobulin G
KW - Antibodies, Blocking
U2 - 10.1016/j.cmi.2023.08.026
DO - 10.1016/j.cmi.2023.08.026
M3 - SCORING: Journal article
C2 - 37661067
VL - 29
SP - 1587
EP - 1594
JO - CLIN MICROBIOL INFEC
JF - CLIN MICROBIOL INFEC
SN - 1198-743X
IS - 12
ER -
