Long-term antibody responses to the Ebola virus and the vaccine vector after rVSV-ZEBOV vaccination in DRC

Abstract

Zaïre ebolavirus (EBOV) remains a serious threat with a high case fatality rate in humans, particularly in the Democratic Republic of Congo (DRC). To cope with previous epidemics, the single-dose and prophylactic rVSV-ZEBOV vaccine was widely applied. However, evidence on the duration of protection and, consequently, the need or timing for booster doses is lacking. Therefore, we investigated in a cross-sectional study design the antibody persistence and neutralizing capacity against three strains of the Orthoebolavirus zaïrense species within healthcare workers (HCWs) who were previously vaccinated in different outbreaks across DRC. The presence of vector-directed immunity was studied via seropositivity to VSV proteins. In total, 133 HCWs were recruited and grouped according to their time from initial vaccination (1-2, 2-3, >3 years), in addition to a control group of 20 unvaccinated HCWs. In 1-2 year vaccinated participants (n = 10), an overall high antibody response (100 % seropositivity) specific to the vaccine-targeted EBOV glycoprotein (GP) of the Kikwit strain was observed, in comparison to <50 % seropositivity to the Mayinga and Kissidougou GP EBOV variants. This antibody trend persisted up to 4 years after vaccination, but overall seropositivity rates decreased to 76.8 % (Kikwit), 38.3 % (Mayinga), and 44.6 % (Kissidougou) for participants vaccinated >3 years ago. Only a minority (n = 6) among all time groups of HCWs with high antibody titers still had demonstrable neutralizing capacity. No persistent VSV-specific antibody responses were observed at any time, suggesting no to low interference with booster doses. Complementing prior findings, our results thus suggest a persistently detectable but strain-specific and slowly declining antibody response to EBOV up to 4 years after vaccination. Our data supports the administration of booster doses after 1-2 years for optimal protection, highlights potential strain-restrictive vaccine-induced immunity, and may inform on correlates of long-term protection.

Keywords: Correlates of protection; Durability; Ebola virus disease; Neutralizing antibody; Strain-specific; Vaccination.