We also observed a dose effect on VSV-EBOV’s immunogenicity. Titers of EBOV-GP-binding and neutralizing antibodies were significantly weaker in low-dose (3 x 105 pfu) recipients, affecting the seropositivity rates of the less sensitive assays. Until correlates of protection against EBOV are established, any prediction as to whether this reduction in antibody titers would have a detrimental effect on protection remains speculative. Assay sensitivities vary substantially, and correlations between antibody titers elicited in VSV-EBOV-immunized non-human primates and humans have not yet been established. Similarly, direct correlations between immune responses elicited in humans by VSV-EBOV and the chimpanzee adenovirus 3 (ChAd3)–vectored vaccine are yet lacking. At high doses (≥107 and 2 x 1011 pfu, respectively), both vaccines appear to elicit initial EBOV-GP-specific responses of a similar magnitude. An advantage of VSV-EBOV, which contributed to its selection for further trials in West Africa, is its anticipated potential as a single-dose vaccine.
6 The end of a trial – and the beginning of everything
The trial, whose follow-up period had been extended from six to 12 months after the emergence of vaccine-related arthritides, terminated on schedule on 26 January 2016. At that time, all cases of arthritis had resolved. No other safety signals emerged in the 12-month post vaccination period. Six-month immune durability data were extremely promising;50 12-month analyses are ongoing. Exploratory analyses of innate responses are also ongoing, as we move closer to understanding how and why certain vaccinees experienced peripheral vaccine virus dissemination, while others did not (manuscript in preparation).
Our trial population is highly unique; they are the first volunteers in the world who were randomized to receive the VSV-EBOV vaccine. Those who received the vaccine at any dose and completed full follow-up (n=100) will soon be asked to participate in a prospective observational cohort study that will launch in November 2016 and evaluate immune durability in the five years following vaccination.
Final note
The VSV-EBOV vaccine was selected for further phase 3 testing in Guinea, Sierra Leone and Liberia. It is also now being used by WHO in an operational ring vaccination strategy whenever additional cases of EVD are diagnosed. Its safety and efficacy require further definition in these target populations. As low-grade, transient symptoms would not impact the use of an effective Ebola vaccine, the further
characterization of frequency and severity of arthritis-, dermatitis- or vasculitis-related symptoms (or sequelae, if any) in African populations will critically inform the development of VSV-EBOV.
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