CEEZAD study finds Use of the Invariant Natural Killer T Cell Agonist α-Galactosylceramide as Adjuvant Can Lead to Vaccine-Associated Enhanced Respiratory Disease in Influenza-Vaccinated Pigs

 

An article co-authored by the Director of the Center of Excellence for Emerging and Zoonotic Animal Diseases (CEEZAD, www.ceezad.org) and the Center on Emerging and Zoonotic Infectious Diseases (CEZID; https://www.k-state.edu/cezid/) discusses findings of recent research linking a Natural Killer T (NKT) cell agonist to enhanced respiratory disease in influenza-vaccinated pigs.

The article was co-authored by Dr. Juergen A. Richt, Regents and University Distinguished Professor at Kansas State University and director of CEEZAD and CEZID. It was published in the September issue of Vaccines.

Other co-authors include Igor Morozov, Taeyong Kwon, Dashzeveg Bold, Velmurugan Balaraman, Bianca Libanori Artiaga, Jamie Henningson, Cassidy Keating, Daniel Madden and Chester McDowell, all of the Department of Diagnostic Medicine and Pathobiology at Kansas State University and CEEZAD.

Invariant natural killer T (iNKT) cells are glycolipid-reactive T cells with potent immunoregulatory properties. iNKT cells activated with the marine-sponge-derived glycolipid, α-galactosylceramide (αGC), are able to provide T cell help that has shown considerable promise for a wide array of therapeutic applications. This includes harnessing iNKT-cell-mediated immune responses to adjuvant whole inactivated influenza virus (WIV) vaccines.

An important concern with WIV vaccines is that under certain circumstances, they are capable of triggering vaccine-associated enhanced respiratory disease (VAERD) in influenza virus infected swine. This immunopathological phenomenon can arise after immunization with an oil-in-water (OIW) adjuvanted WIV vaccine, followed by infection with a hemagglutinin and neuraminidase mismatched challenge influenza virus. This elicits antibodies (Abs) that bind immunodominant epitopes in the HA2 region of the heterologous virus, which supposedly can cause enhanced virus fusion activity to the host cell and increased infection.

In this recently published research, CEEZAD scientists showed that αGC can induce severe VAERD in pigs. However, instead of stimulating high concentrations of HA2-specific Abs, αGC elicits high concentrations of interferon (IFN)-γ-secreting cells, both in the lungs and systemically. Additionally, the study found that VAERD mediated by iNKT cells results in distinct cytokine profiles and altered adaptation of the challenge virus following infection when compared to an OIW adjuvant.

Overall, these results provide a cautionary note about considering the formulation of WIV vaccines with iNKT-cell agonists as a potential strategy to modulate antigen-specific immunity.