Asian Elephant mRNA Vaccine Restrains Viremia and Prevents Disease Following Primary Infection
Background
Elephant endotheliotropic herpesvirus 1A (EEHV1A) causes a fatal hemorrhagic disease in young Asian elephants. The period when maternal antibodies wane but natural immunity has not yet developed is particularly risky. Infection leads to rapid vascular endothelial cell damage and systemic hemorrhage, making it a major cause of death in young Asian elephants in zoos.
Early detection through genetic testing and administration of antiviral drugs are used, but the therapeutic effect is inconsistent, and the condition can rapidly worsen after the onset of symptoms. The difficulty in stably culturing the virus in the laboratory has also hindered the development of traditional attenuated or inactivated vaccines. To overcome these limitations, researchers designed a multivalent messenger RNA (mRNA) vaccine using four viral glycoproteins (gB, gH, gL, and gO) that the virus uses to attach to and fuse with host cells.
Key Findings
The researchers observed two 6- and 7-year-old male Asian elephants that were transferred from Dublin Zoo to the Cincinnati Zoo and Botanical Garden in November 2023. Both individuals were seronegative for EEHV1A. They received the experimental vaccine for the first time in October 2024, followed by a booster dose in the same month.
After vaccination, antibodies recognizing all four glycoproteins significantly increased. However, the antibody titers began to decrease 102 days after the booster dose, indicating that the duration of immunity may not be indefinite. Subsequently, the younger individual and the older individual developed EEHV1A viremia in February and March 2025, respectively. The vaccine did not completely prevent infection.
The clinical course differed from typical high-risk primary infections. In both individuals, the viral load in the blood remained below 6,000 viral genome equivalents (VGE)/mL, and no hematological abnormalities or hemorrhagic disease symptoms were observed. The virus was cleared without antiviral treatment, and their health was maintained. The antibody titers against the four antigens measured after viremia were close to the levels observed in elephants that had experienced natural infection, suggesting that the infection may have re-stimulated the immune memory.
Significance and Outlook
These results suggest that the vaccine may have induced a defensive immunity that suppresses viral replication to a low level, preventing the disease from progressing to a fatal stage, rather than a sterilizing immunity that blocks EEHV1A invasion. This study represents an early example of applying a herpesvirus mRNA vaccine to actual target species, and, according to the researchers, the first use of mRNA vaccines in endangered mammals.
However, the observation was limited to two individuals, and there was no unvaccinated control group, so it is not yet possible to confirm the efficacy. It is also possible that the two individuals would not have developed severe disease anyway. It remains to be determined how much neutralizing antibodies and cellular immunity contribute to protection, and when booster doses should be administered in response to the decline in antibody levels. Only by collecting long-term follow-up data from elephants vaccinated at multiple facilities and comparing the severity and survival rates can the preventive effect of the vaccine be quantitatively assessed.
UNLABELLED: Juvenile Asian elephants who have lost maternal antibodies are particularly susceptible to fatal hemorrhagic disease caused by primary infection with elephant endotheliotropic herpesvirus 1A (EEHV1A). To address this vulnerability, a multi-antigen EEHV1A mRNA vaccine has been administered to EEHV1A seronegative calves at four institutions. However, the extent to which this vaccine confers protective immunity remains an open question. In November 2023, two juvenile male calves (aged 6 and 7 years) were transferred from Dublin Zoo to the Cincinnati Zoo and Botanical Garden and confirmed to be seronegative for EEHV1A. Both calves received an experimental EEHV1A mRNA vaccine in October 2024, followed by a booster dose in November. Post-vaccination serological responses were robust, with significant antibody production against vaccine-encoded glycoproteins (gB, gH, gL, and gO), although titers started to decline by day 102 post-booster. In February 2025, the younger calf developed EEHV1A viremia, followed by the older calf in March. Both maintained viral loads below 6,000 viral genome equivalents (VGE)/mL and exhibited no hematological abnormalities or clinical signs of disease. Serum collected post-viremia revealed sustained antibody titers against the four vaccine antigens, approaching levels observed in naturally infected elephants. Despite confirmed viremia, both calves remained clinically healthy, and viral loads resolved without therapeutic intervention. These findings suggest that immunity generated against the EEHV proteins encoding the conserved herpesvirus attachment fusion complex can confer protective immunity and mitigate disease severity following primary infection in juvenile elephants. IMPORTANCE: This study delivers an early demonstration of applying mRNA vaccination to a herpesvirus outside conventional laboratory models and, to our knowledge, the first such use in an endangered mammalian species. EEHV-HD is the leading cause of death in juv
In zoos and conservation facilities, it may be possible to select young elephants with declining maternal antibodies, vaccinate them, and then monitor antibody titers and EEHV levels in the blood after booster doses. If infection is confirmed, the low viral load and normal blood tests may provide a basis for reducing unnecessary treatment.
Industrially, this demonstrates that even for wild animal viruses that are difficult to culture, vaccine candidates can be rapidly produced by simply obtaining the nucleotide sequence and combining multiple antigens. However, before actual implementation, standardization of dosage, booster schedule, and storage/transport conditions, as well as larger-scale safety and efficacy data, are required.