Duck IL-7 as a novel adjuvant improves the humoral immune response to an inactivated duck tembusu virus vaccine.

Duck tembusu virus (DTMUV), belonging to the Flavivirus genus, Flaviviridae family, has caused huge economic losses in the duck industry. However, the inactivated DTMUV vaccine requires multiple immunizations and has incomplete effectiveness. The humoral immune response is a key factor in the control of DTMUV infection. IL-7 derived from mammals has the ability to enhance antibody production. Whether duck IL-7 (duIL-7) possesses the ability to improve the humoral immunity of inactivated DTMUV vaccine has not yet been declared. Here, a beta-propiolactone (BPL)-inactivated DTMUV vaccine was employed to characterize the adjuvant property of duIL-7 in humoral immune responses. Intramuscular injection of DTMUV inactivated vaccine with or without duIL-7 was administered twice to the ducks. The results showed that duIL-7 was able to promote rapid antibody responses and enhance DTMUV-specific IgG and neutralizing antibody production to the vaccine. T follicular helper (Tfh) cells play a key role in assisting long humoral immunity. It was found that duIL-7 upregulated duIl-6 and duIl-21 gene expression at 3 w post first vaccination, which encode Tfh cell differentiation-related cytokines duIL-6 and duIL-21, respectively. This may be the reason that duIL-7 could prolong the humoral immune response to the inactivated DTMUV vaccine. Next, the ability of duIL-7 to simplify the immunization procedure of the inactivated DTMUV vaccine was tested. When ducks were immunized once, the titers of neutralizing antibodies in ducks from the inactivated DTMUV vaccine supplemented with duIL-7 group were significantly higher than those of ducks from the inactivated DTMUV vaccine group (P < 0.05). In addition, duIL-7 could assist the inactivated DTMUV vaccine in maintaining neutralizing antibodies at high levels during the whole experimental period. The viral titers in the ducks immunized with the inactivated DTMUV vaccine and duIL-7 were lower than those in the ducks immunized with the inactivated DTMUV vaccine alone at 3 days post infection (3 dpi, P < 0.05). Overall, duIL-7 possessed the ability to promote and prolong humoral immune responses to the inactivated DTMUV vaccine, even at one dose. This study provides a new efficient adjuvant for inactivated DTMUV vaccine development.

The Broad Immunomodulatory Effects of IL-7 and Its Application In Vaccines.

Interleukin-7 (IL-7) is produced by stromal cells, keratinocytes, and epithelial cells in host tissues or tumors and exerts a wide range of immune effects mediated by the IL-7 receptor (IL-7R). IL-7 is primarily involved in regulating the development of B cells, T cells, natural killer cells, and dendritic cells via the JAK-STAT, PI3K-Akt, and MAPK pathways. This cytokine participates in the early generation of lymphocyte subsets and maintain the survival of all lymphocyte subsets; in particular, IL-7 is essential for orchestrating the rearrangement of immunoglobulin genes and T-cell receptor genes in precursor B and T cells, respectively. In addition, IL-7 can aid the activation of immune cells in anti-virus and anti-tumor immunity and plays important roles in the restoration of immune function. These biological functions of IL-7 make it an important molecular adjuvant to improve vaccine efficacy as it can promote and extend systemic immune responses against pathogens by prolonging lymphocyte survival, enhancing effector cell activity, and increasing antigen-specific memory cell production. This review focuses on the biological function and mechanism of IL-7 and summarizes its contribution towards improved vaccine efficacy. We hope to provide a thorough overview of this cytokine and provide strategies for the development of the future vaccines.