Co-administration of chicken IL-2 alleviates clinical signs and replication of the ILTV chicken embryo origin vaccine by pre-activating natural killer cells and cytotoxic T lymphocytes

ABSTRACT The chicken embryo origin (CEO) vaccine of infectious laryngotracheitis virus (ILTV) confers the best protection against ILTV but causes adverse reactions due to its swift replication, thus limiting its use in poultry flocks. Seeking a strategy to alleviate the adverse reactions of the vaccine is most desirable for its safe use. Here, we observed that co-administration of chIL-2 significantly alleviated the clinical signs induced by the CEO vaccine in chickens. To address the underlying mechanism, we examined the cellular immune response of chickens treated with or without chIL-2 by multicolor flow cytometry and evaluated the impact of chIL-2 on the protective efficacy and replication of the CEO vaccine after the challenge. The results showed that co-administration of chIL-2 was associated with a decrease in the clinical signs and CEO viral load in tissues and induced a rapid and significant expansion of natural killer (NK) cells and cytotoxic T lymphocytes (CTLs) as well as upregulated expression of cytotoxic and T-cell-related cytokines at the early stage, especially in trachea and conjunctiva. However, chIL-2 treatment has no negative effect on the recall responses of NK cells, γδ T cells, and CTLs associated with the protective efficacy of the CEO vaccine after the ILTV challenge. Collectively, our results suggest that co-administration of chIL-2 with the CEO vaccine ameliorated the replication of the CEO vaccine by enhancing chicken NK cell and CTLs responses without affecting its protective efficacy. IMPORTANCE Chickens immunized with the infectious laryngotracheitis chicken embryo origin (CEO) vaccine (Medivac, PT Medion Farma Jaya) experience adverse reactions, hindering its safety and effective use in poultry flocks. To improve the effect of the vaccine, we sought to find a strategy to alleviate the respiratory reactions associated with the vaccine. Here, we confirmed that co-administering the CEO vaccine with chIL-2 by oral delivery led to significant alleviation of the vaccine reactions in chickens after immunization. Furthermore, we found that the co-administration of chIL-2 with the CEO vaccine reduced the clinical signs of the CEO vaccine while enhancing natural killer cells and cytotoxic T lymphocyte response to decrease viral loads in their tissues, particularly in the trachea and conjunctiva. Importantly, we demonstrated that the chIL-2 treatment can ameliorate the replication of the CEO vaccine without compromising its effectiveness. This study provides new insights into further applications of chIL-2 and a promising strategy for alleviating the adverse reaction of vaccines. Chickens immunized with the infectious laryngotracheitis chicken embryo origin (CEO) vaccine (Medivac, PT Medion Farma Jaya) experience adverse reactions, hindering its safety and effective use in poultry flocks. To improve the effect of the vaccine, we sought to find a strategy to alleviate the respiratory reactions associated with the vaccine. Here, we confirmed that co-administering the CEO vaccine with chIL-2 by oral delivery led to significant alleviation of the vaccine reactions in chickens after immunization. Furthermore, we found that the co-administration of chIL-2 with the CEO vaccine reduced the clinical signs of the CEO vaccine while enhancing natural killer cells and cytotoxic T lymphocyte response to decrease viral loads in their tissues, particularly in the trachea and conjunctiva. Importantly, we demonstrated that the chIL-2 treatment can ameliorate the replication of the CEO vaccine without compromising its effectiveness. This study provides new insights into further applications of chIL-2 and a promising strategy for alleviating the adverse reaction of vaccines.