With no vaccine yet developed against the Bundibugyo virus (BDBV) species of orthoebolaviruses currently circulating in the Democratic Republic of Congo (DRC), the outbreak is anticipated to exceed the 2013-2016 epidemic. Investigators now report on the first longitudinal study in humans to seek evidence that an older vaccine targeting Ebola virus (EBOV) might offer some protection. 1
"As public health authorities respond to the ongoing outbreak, an important question is whether currently licensed Ebola virus disease vaccines generate cross-reactive immune responses that might be relevant to evaluate during the current outbreak," explain Megan Halbrook, PhD, Department of Epidemiology, University of California, Los Angeles, and colleagues.
The investigators identified 482 individuals in Mbandaka, Equateur Province and 505 in Beni, North Kivu Province who had received the rVSV∆-ZEBOV-GP vaccine in 2018 during the WHO ring-vaccination response to the EBOV outbreak, and had provided serologic samples in 7 data collections over 5 years. The longitudinal cross-reactive antibody response to the EBOV and non-EBOV species after receiving the rVSV∆-ZEBOV-GP vaccine was assessed by a pan-filovirus multiplex immunoassay, with seroreactivity expressed in units of median fluorescent intensity (MFI).
Both regions had experienced recurrent outbreaks with multiple Orthoebolavirus species in that period. The investigators found that at baseline, 16 (3%) of the Mbandaka cohort and 62 (10%) in Beni had been seroreactive to BDBV glycoprotein. In Mbandaka, BDBV glycoprotein antibody reactivity remained stable at 6 months after vaccination, before increasing from a mean MFI of 1238 at 2.5 years with 16 (5%) seroreactive, to 4845 at 3.5 years with 116 (35%) seroreactive. In Beni, BDBV reactivity increased rapidly after vaccination to mean MFI of 6678 with 283 (52%) seroreactive at 21 days; and to a mean MFI of 6852 with 270 (54%) seroreactive at 6 months.
"The differing patterns of BDBV glycoprotein seroreactivity observed between Beni and Mbandaka warrant further investigation into the epidemiological and immunological factors associated with this seroreactivity, including the epidemiological significance of baseline seroreactivity observed before vaccination," Halbrook and colleagues commented.
Among the factors not related to vaccination that they suggest could have influenced BDBV glycoprotein seroreactivity, are previous filovirus exposure, immune priming, and environmental or other epidemiological conditions. They also speculate that the differing anti-BDBV antibody reactivity trajectories in the 2 communities could arisefrom such factors as variation in exposures before and during the study period, and undocumented filovirus exposures.
What You Need to Know
In a five-year longitudinal study of over 900 outbreak-affected individuals in the DRC, the licensed rVSV∆-ZEBOV-GP Ebola vaccine (targeting the Zaire species) was associated with cross-reactive antibody responses to the Bundibugyo species (BDBV), the strain now driving the current outbreak.
Seroreactivity patterns differed markedly between the two study sites—rising slowly over years in Mbandaka versus spiking rapidly within weeks in Beni—suggesting factors beyond vaccination, such as prior filovirus exposure, may shape the response.
Commentators caution that since the study measured only antibody presence rather than neutralizing capacity, the actual protective benefit against BDBV remains unproven, and deploying the vaccine on this basis risks fostering false complacency that could increase transmission.
In accompanying commentary, Abhishek Prasad, PhD and Thomas Geisbert, PhD, Glveston National Laboraty, University of Texas Medical Branch, Galveston, TX, note that this study, like the earlier PREVAC trial "are limited in that they only measured the presence and relative magnitude of BDBV-reactive antibodies but cannot be used to establish whether these antibodies are neutralizing, or non-neutralising and what degree of protection, if any, they confer."2-3
Prasad and Geisbert acknowledge the urgent need to contain the outbreak and mitigate human suffering, but advise of unintended consequences that could follow distribution of an unproven vaccine.
They warn, for example, "vaccination can induce complacency in health-care workers and community members, where the assumption of immunity might lead to the relaxation of infection avoidance measures and result in increased transmission if the vaccine is not fully protective."
Read more about the US policies around the disease: Ebola and the Ongoing Tale of US Failures
References
1. Halbrook M, Merritt S, Hoff NA, et al. Bundibugyo virus glycoprotein seroreactivity following recombinant vesicular stomatitis virus-Zaire Ebola virus glycoprotein vaccination in outbreak-affected populations of the Democratic Republic of the Congo: a longitudinal cohort study. The Lancet. 2026; 408:1019-1028.
2. Prasad AN, Geisbert TW. rVSV∆-ZEBOV-GP vaccine-induced seroreactivity to Bundibugyo virus: a cross-protection dilemma. The Lancet. 2026; 408:973-976.
3. Lhomme E, Wiedeman A, Ayouba, A, et al. Cross-reactive Bundibugyo antibody responses after receipt of licensed Ebola vaccines. N Engl J Med. 2026; 395:612-615.
