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.