Abstract
Ebolaviruses pose significant public health problems due to their high lethality, unpredictable emergence, and localization to the poorest areas of the world. In addition to implementation of standard public health control procedures, a number of experimental human vaccines are being explored as a further means for outbreak control. Recombinant cytomegalovirus (CMV)-based vectors are a novel vaccine platform that have been shown to induce substantial levels of durable, but primarily T-cell-biased responses against the encoded heterologous target antigen. Herein, we demonstrate the ability of rhesus CMV (RhCMV) expressing Ebola virus (EBOV) glycoprotein (GP) to provide protective immunity to rhesus macaques against lethal EBOV challenge. Surprisingly, vaccination was associated with high levels of GP-specific antibodies, but with no detectable GP-directed cellular immunity.
Highlights
Ebolaviruses pose significant public health problems due to their high lethality, unpredictable emergence, and localization to the poorest areas of the world
This resulted in deletion of the rhesus CMV (RhCMV) Rh112 open-reading frame (ORF), an ORF known to be dispensable for secondary RhCMV infection and virus persistence[29]
The ability of a recombinant RhCMV deleted for Rh112 to induce T cell responses against its heterologous expressed simian immunodeficiency virus (SIV) target antigen shows that Rh112 is not required for induction of T cell immunity in CMV-immune NHPs29
Summary
Ebolaviruses pose significant public health problems due to their high lethality, unpredictable emergence, and localization to the poorest areas of the world. Results from experimental animal studies using these vaccines indicate that antibody and cellular immunity can be important for protection against EBOV8. Interim results from an ongoing phase 3 cluster randomized trial indicate that at least one of these candidates, based on vesicular stomatitis virus, may be highly efficacious and safe[9]. It remains to be seen whether the other vaccine candidates currently in human clinical trials will prove as protective against EBOV, and which immunological mechanisms are involved
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