Efficacy of recombinant Marek’s disease vaccine 301B/1 expressing membrane-anchored chicken interleukin-15

Authors: Kim, Taejoong; Hearn, Cari; Heidari, Mohammad

Submitted to: Avian Diseases
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 3/24/2024
Publication Date: 4/8/2024
Citation: Kim, T.N., Hearn, C.J., Heidari, M. 2024. Efficacy of recombinant Marek’s disease vaccine 301B/1 expressing membrane-anchored chicken interleukin-15. Avian Diseases. 68(2):117-128. https://doi.org/10.1637/aviandiseases-D-23-00068.
DOI: https://doi.org/10.1637/aviandiseases-D-23-00068

Interpretive Summary: Marek’s disease (MD) is an economically important disease of chickens characterized by T cell tumors and a suppressed immune system in susceptible birds. Since the late 1960s, MD has been controlled by mass vaccination of commercial flocks. However, as the Marek’s disease virus (MDV), the causative agent, has repeatedly evolved to evade MD vaccines, there is a need for new and improve vaccines. In this study, we generated a recombinant MD vaccine candidate that also expresses cytokine IL-15 to enhance the immune response to MDV infection. The expression of IL-15 was confirmed in vaccinated animals and, more importantly, the activation of an important immune cell type, natural killer (NK) cells, was also verified. However, the protection afforded by the recombinant MD vaccine was not improved compared to the original MD vaccine. Nonetheless, this strategy to express immunomodulators should be explored further in the rational design of new vaccines.

Technical Abstract: Cytokines are co-administrated with vaccines or co-expressed in the vaccine virus genome to improve protective efficacy by stimulating immune responses. Using glycosylphosphatidylinositol (GPI) anchoring by attachment to the target cytokine, we constructed recombinant MDV vaccine strain 301B/1 (v301B/1-rtg-IL-15) that expresses chicken interleukin-15 (IL-15) as the membrane-bound form at the cell -surface. We evaluated the vaccine efficacy of v301B/1-rtg-IL-15 given as a bivalent MD vaccine in combination with turkey herpesvirus (HVT) against a very virulent plus MDV strain 648A challenge. The efficacy was compared with that of conventional bivalent MD vaccine, as a mixture with HVT plus parental v301B/1 or v301B/1-IL-15, which expresses a natural form of IL-15. The membrane-bound IL-15 expression did not interfere with the virus growth of recombinant v301B/1-rtg-IL-15. However, the MD incidence in birds vaccinated with v301B/1-rtg-IL-15 was higher than that of conventional bivalent MD vaccine containing parental v301B/1 virus although the v301B/1-rtg-IL-15 vaccinated group showed increased natural killer cell activation at day 5 of vaccination, the same day as challenge. Overall, the protection of v301B/1-rtg-IL-15 was not improved from that of v301B/1 against very virulent plus MDV challenge.