A safe, T cell-inducing heterologous vaccine against elephant endotheliotropic herpesvirus in a proof-of-concept study

Journal article

We report the results of the world’s first trial of a vaccine against elephant endotheliotropic herpesvirus (EEHV) in elephants. EEHV-induced haemorrhagic disease is a major threat to juvenile Asian elephants. A vaccine preventing severe disease and death would support conservation efforts for this endangered species. We developed a heterologous, recombinant modified vaccinia virus Ankara prime and adjuvanted protein boost vaccine, containing regulatory protein EE2 and major capsid protein. Vaccine design targeted Th1 and cytotoxic T cell responses, crucial for herpesvirus immunity. In a proof-of-concept trial, safety and immunogenicity were tested in adult elephants. A modified interferon-γ release (IFNG) point-of-care vaccine-specific whole blood assay was established to avoid sample transport-related loss of immune readouts and determine T cell responses by RT-qPCR first. Subsequently, RNA sequencing was utilised to investigate transcriptomic changes post-vaccination. No adverse reactions were observed following heterologous vaccination. IFNG responses to candidate antigens were detected against the pre-existing latent immunity in adult elephants. Over-representation analysis revealed induction of T cell-associated pathways. Thus, we show that the vaccine has a favourable safety profile and stimulates EEHV-specific T cell-biased immune responses, warranting further evaluation.

Authors: Maehr, T; Lopez, J; Drake, G; Ferreira, FM; Fraser, R

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: Nature Research
• Journal: Nature Communications
• Volume: 16
• Issue: 1
• Article number: 8374
• Publication date: 2025-10-03
• Acceptance date: 2025-09-01
• DOI: 10.1038/s41467-025-64004-x
• EISSN: 2041-1723
• ISSN: 2041-1723
• Language: English