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

Tanja Maehr (), Javier Lopez, Gabby Drake, Frederico M. Ferreira, Richard Fraser, Rebecca Mckown, Reshma Kailath, Susan Morris, Adam Chambers, Leo P. Graves, Susan L. Walker, Akbar Dastjerdi, Katie L. Edwards, Helder I. Nakaya and Falko Steinbach ()
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Tanja Maehr: University of Surrey
Javier Lopez: Chester Zoo
Gabby Drake: Chester Zoo
Frederico M. Ferreira: University of São Paulo Medical School
Richard Fraser: Chester Zoo
Rebecca Mckown: Chester Zoo
Reshma Kailath: University of Oxford
Susan Morris: University of Oxford
Adam Chambers: Bioinnovation Hub
Leo P. Graves: Bioinnovation Hub
Susan L. Walker: Chester Zoo
Akbar Dastjerdi: Animal and Plant Health Agency (APHA) Weybridge
Katie L. Edwards: Chester Zoo
Helder I. Nakaya: Hospital Israelita Albert Einstein
Falko Steinbach: University of Surrey

Nature Communications, 2025, vol. 16, issue 1, 1-15

Abstract: Abstract 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.

Date: 2025
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DOI: 10.1038/s41467-025-64004-x

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