a t cell-inducing prime-boost vaccine for elephant endotheliotropic herpesvirus (eehv)

Elephant endotheliotropic herpesviruses (eehv) are a major threat to juvenile asian elephants due to eehv induced haemorrhagic disease (eehv-hd). there are no efficacious antiviral therapies or vaccines yet. notably, the target cells for eehv in vivo are unclear and monocytes/macrophages have been proposed as such. since immunity against herpesviruses relies on cellular responses, we aimed to devise a t cell-inducing vaccine. accordingly, we applied reverse vaccinology techniques to design an eehv vaccine that prevents death and severe disease not using external (glycoprotein) antigens. specifically, we used a modified vaccinia ankara (mva) viral vector as priming vaccine and an adjuvanted protein formulation each containing two antigens as boost, creating a heterologous prime-boost vaccine. in a first-in-elephant proof-of-concept trial, this prototype vaccine was tested for safety (and immunogenicity) in three adult elephants. we used a modified ifn-g release point-of-care, vaccine-specific whole blood stimulation assay to determine immune responses with rt-qpcr as first readout. a complete lack of adverse reactions post-vaccination strongly suggests that this heterologous prime-boost vaccine can be safely used in elephants. recall ifn-g responses to our candidate antigens were observed against a background of reactions caused by the latent infection that exists in all elephants. of diagnostic value for the immune reaction were abs that could be detected against the candidate antigens using western blot. rna from preserved stimulated whole blood was used to determine the immune reaction via rna sequencing and assessment of differential gene expression pre- vs. post-vaccination. over representation gene analysis (ora) demonstrated that the vaccine induced a cd8+ and cd4+ t cell-based immune cell composition. further deg analysis demonstrated the th1 bias of the antigen-specific immune response. these results support a further evaluation of this prototype vaccine in young elephants as the target population for vaccination against eehv-hd.