Abstract

Antibody responses to rVSV-ZEBOV vaccination for Ebola virus disease across doses and continents: five-year durability

Huttner A, Agnandji ST, Engler O, Hooper JW, Kwilas S, Ricks K, Clements TL, Jonsdottir HR, Nakka SS, Rothenberger S, Kremsner P, Z?st R, Medaglini D, Ottenhoff T, Harandi AM, Ca S
Clin Microbiol Infect. 2023;S1198-743X

Permenent descriptor

OBJECTIVES: To report five-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 2014-5 were followed for up to four (Lambar?n?, Gabon) and five (Geneva, Switzerland) years. We report seropositivity rates, geometric mean titres (GMTs) and population distribution of ZEBOV-GP ELISA IgG antibodies, neutralising antibodies (pseudovirus and live-virus neutralisation) and antibody avidity; the primary outcome was ZEBOV-GP ELISA IgG GMTs at four or five years compared to one year (Y1) after immunisation. RESULTS: Among the 168 eligible vaccinees (Geneva: 97, Lambar?n?: 71) enrolled one-year post-immunisation, 146 (87%) remained enrolled at four years (Geneva: n=88, Lambar?n?: n=58) and 84 (87%, Geneva) at five years post-vaccination. ZEBOV-GP ELISA IgG GMTs plateaued, with no declining trend from one 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 pfu of rVSV-ZEBOV), their avidity matching that of ZEBOV convalescents. Live-virus neutralising 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). CONCLUSIONS: 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 neutralising antibodies suggests the contribution of antibody-mediated protective mechanisms other than neutralisation. Long-term clinical efficacy of rVSV-ZEBOV, however, requires further study.