SHIC-Funded Work Determines Human JEV Vaccine May Work for Pigs

The Swine Health Information Center funded a study to evaluate potential tools to protect swine health and mitigate the impact of Japanese encephalitis virus infection in pigs. Led by Dr. Thomas P. Monath with Substipharma Biologics SA, the study sought to determine whether an existing single-dose JEV vaccine for humans has the potential to be safe and effective to prevent infection, clinical disease in swine, and transmission of the virus.

Find the industry summary for SHIC project #24-056 here.

JEV is not currently established in the mainland United States, but its introduction could create significant animal health and public health concerns. Pigs can play an important role in the JEV transmission cycle by amplifying the virus, making the swine population an important consideration in an emergency response. JEV is transmitted principally by mosquitoes, using pigs and birds as amplifying hosts, with spillover to humans. JEV affects a wide area of temperate and tropical parts of the Asia–Pacific region. The 2022 expansion of JEV in continental Australia has raised awareness of the threat to the US.

Although routine JEV vaccination of swine is practiced in some Asian countries, there are no veterinary vaccines currently approved for use in the US. An effective swine vaccine could become an important tool to reduce the amount of virus circulating in a population and limit the role pigs play in JEV amplification during an outbreak.

Investigation of the impact of JEV vaccination in pigs

ImoJev^® is a recombinant live, attenuated vaccine using the yellow fever 17D vaccine as a vector for expressing the prM-E envelope genes of an attenuated Japanese encephalitis vaccine strain SA-14-14-2 widely used in parts of Asia for human immunization. The study to investigate the potential impact of the use of this vaccine included three primary objectives 1) demonstrate the efficacy of ImoJev^® in protecting pigs from challenge with JEV, 2) demonstrate the safety and immunogenicity of ImoJev^® in swine, and 3) demonstrate the minimum effective dose for immunization with ImoJev^®.

US crossbred pigs ranging from 6-8 weeks of age were utilized during the study and were tested to determine West Nile Virus serostatus. Rectal temperatures were tracked for all pigs. The virus for the pig challenge model used viremia as the indicator of protection against JEV (genotype IV) peripheral challenge which does not cause clinical illness. Samples collected during the study included blood (viremia, WNV serostatus and antibody detection), nasal, oral and rectal swabs (viral plaque assay) , and the brainstem (medulla) and cerebrum for tissue lesions, histology, and viral plaque assay.

The study identified important differences between humans and pigs

Across the studies, vaccinated pigs developed neutralizing antibodies and demonstrated substantially lower levels of JEV in their blood following exposure to the challenge virus. In one challenge study, all pigs receiving the two-dose intramuscular vaccination program were protected from detectable viremia, with only one animal showing a very low-level breakthrough infection. Lower virus levels in infected pigs could reduce the potential for pigs to amplify JEV and contribute to transmission and could protect pregnant sows from abortion and stillbirth.

The subsequent dose-range experiment reinforced the finding that pigs receiving two doses had significantly lower peak virus levels and overall virus exposure than unvaccinated control animals. The levels of viremia observed in vaccinated pigs were substantially below those considered necessary for efficient infection of mosquito vectors.

Neutralizing antibody levels against four JEV genotypes elicited by the vaccine exceeded the 1:10 threshold for protection (correlate of protection) established for humans.

No safety signals nor vaccine shedding were detected in pigs receiving the ImoJev® vaccine. The results indicated that two intramuscular doses were required for robust, consistent immunogenicity. Unlike the human vaccination program, pigs required a higher vaccine dose and a two-dose schedule to produce a robust and consistent immune response. Intramuscular administration also produced the most reliable results.

More work is needed before a vaccine could be used

Additional research is needed to demonstrate the protective threshold for all five JEV genotypes and to show protection against viremia and disease in pigs challenged with both homologous and heterologous JEV genotype viruses. It cannot be predicted which JEV genotype would be introduced into the US. A better challenge model system with adverse clinical outcomes (other than viremia) would be required to support experimental studies.

While the vaccine proved to be less immunogenic in pigs than in nonhuman primates and humans, it could potentially be utilized as a veterinary vaccine for emergency preparedness against a JEV introduction into the US swine population.

The Swine Health Information Center, launched in 2015 with Pork Checkoff funding, protects and enhances the health of the US swine herd by minimizing the impact of emerging disease threats through preparedness, coordinated communications, global disease monitoring, analysis of swine health data, and targeted research investments. As a conduit of information and research, SHIC encourages sharing of its publications and research. Forward, reprint, and quote SHIC material freely. For more information, visit https://www.swinehealth.org or contact Dr. Lisa Becton at [email protected].