reported the critical role of antibodies in rVSV-mediated protection, and a limited role of CD8+ T cells32,35. 8-week interval in humans by immunobridging. Immunogenicity and protective efficacy data were obtained for Ad26.ZEBOV and MVA-BN-Filo vaccine regimens using a fully lethal EBOV Kikwit challenge model in cynomolgus monkeys (nonhuman primates [NHP]). The association between EBOV neutralizing antibodies, glycoprotein (GP)-binding antibodies, and GP-reactive T cells and survival in NHP was assessed by logistic regression analysis. Binding antibodies against the EBOV surface GP were identified as the immune parameter with the strongest correlation to survival post EBOV challenge, and used to infer the predicted protective effect of the vaccine in humans using published data from phase I studies. The human vaccine-elicited EBOV GP-binding antibody levels are in a range associated with significant protection against mortality in NHP. Based on this immunobridging analysis, the EBOV GP-specific-binding antibody levels elicited by the Ad26.ZEBOV, MVA-BN-Filo vaccine regimen in humans will likely provide protection against EBOV disease. Subject terms: Immunology, Vaccines Introduction The frequency and magnitude of Ebola computer virus (EBOV) outbreaks are apparently around the increase1, emphasizing the need for prophylactic vaccines2, as well as reactive vaccination and other steps to rapidly contain outbreaks. However, conducting traditional randomized controlled efficacy studies of a prophylactic Ebola vaccine is only feasible in large outbreaks Hesperidin and brings logistical difficulties. Anticipating circumstances under which vaccine efficacy demonstration may not be technically or ethically feasible, guidelines for demonstrating a likelihood of clinical benefit include: the FDA Animal Rule3, European Medicine Agency conditional approval4 or approval under outstanding circumstances5, and Health Canada extraordinary use of a new drug6. These guidelines stipulate that an immunological marker that correlates with protection in a suitable animal model could be used to demonstrate likelihood of clinical benefit as a basis for licensure, with additional postlicensure commitments. Recently, BioThrax? became the first vaccine licensed under the FDA Animal Rule7. While immunobridging assumes that this protective mechanism is usually conserved between the animal model and humans, the immunological marker selected for immunobridging only needs to correlate with the desired benefit, and is not necessarily involved in the mechanism of protection3. For EBOV disease (EVD), nonhuman primates (NHP) are the most relevant animal model8,9, exhibiting Hesperidin the major hallmarks of hemorrhagic fever such as clotting abnormalities Hesperidin as well as liver and kidney damage, albeit with differences in disease course and severity associated with a higher lethality rate10. In this case, cynomolgus monkeys (value for the effect of viral weight?ITGB3 EVD. At the selected challenge dose of 100 pfu the model is usually stringent, with 100% mortality and extremely rapid disease progression, and is considered an acceptable model of human EVD by regulatory government bodies. GP-binding antibodies were selected as the immunological marker from which to infer the vaccine protective effect in humans, i.e., immunobridging, based on human immunogenicity data obtained in the same assay. The outcome of this exploratory immunobridging analysis indicates that it is highly likely that this immune response.
reported the critical role of antibodies in rVSV-mediated protection, and a limited role of CD8+ T cells32,35