Fusion Cytokines IL-7-Linker-IL-15 Promote Mycobacterium Tuberculosis Subunit Vaccine to Induce Central Memory like T Cell-Mediated Immunity

Abstract

Tuberculosis (TB), caused by Mycobacterium tuberculosis (M. tuberculosis), is among the most serious infectious diseases worldwide. Adjuvanted protein subunit vaccines have been demonstrated as a kind of promising novel vaccine. This study proposed to investigate whether cytokines interliukine-7 (IL-7) and interliukine-15 (IL-15) help TB subunit vaccines induce long-term cell-mediated immune responses, which are required for vaccination against TB. In this study, mice were immunized with the M. tuberculosis protein subunit vaccines combined with adnovirus-mediated cytokines IL-7, IL-15, IL-7-IL-15, and IL-7-Linker-IL-15 at 0, 2, and 4 weeks, respectively. Twenty weeks after the last immunization, the long-term immune responses, especially the central memory-like T cells (TCM like cell)-mediated immune responses, were determined with the methods of cultured IFN-γ-ELISPOT, expanded secondary immune responses, cell proliferation, and protective efficacy against Mycobacterium bovis Bacilli Calmette-Guerin (BCG) challenge, etc. The results showed that the group of vaccine + rAd-IL-7-Linker-IL-15 induced a stronger long-term antigen-specific TCM like cells-mediated immune responses and had higher protective efficacy against BCG challenge than the vaccine + rAd-vector control group, the vaccine + rAd-IL-7 and the vaccine + rAd-IL-15 groups. This study indicated that rAd-IL-7-Linker-IL-15 improved the TB subunit vaccine’s efficacy by augmenting TCM like cells and provided long-term protective efficacy against Mycobacteria.

The effect of previous SARS-CoV-2 infection on systemic immune responses in individuals with tuberculosis

“…Our findings showed that the TB/Prex-SCoV-2 group had lower amounts of systemic soluble factors such GM-CSF ( 29 ), IL-15 ( 30 ), IL-1β ( 31 ), IL-7 ( 30 ), TNF-β ( 32 ), IL-12(p70) ( 33 ), IL-17 all of which are considered essential for Mtb control ( 34 ). Nevertheless, there was no difference in the bacillary load in sputum when compared to the TB group.…”

Randomized, Double-Blind, Placebo-Controlled Trial of MUC1 Peptide Vaccine for Prevention of Recurrent Colorectal Adenoma

“…Phosphodiesterase inhibitors inhibit MDSC (42), as does priming with systemic poly IC-LC (19). Administration of cytokines such as IL-7 and IL-15 could promote T cell functioning (43).…”

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

“…Similarly, recombinant NDV expressing mIL-7/ mIL-15 also improved the anti-tumor activity of the NDV LX strain (166), while the delivery of mIL-7/mIL-15 co-expression plasmids as molecular adjuvants with the Toxoplasma gondii calcium-dependent protein kinase 1 (TgCDPK1) DNA vaccine enhanced Toxoplasma-specific IgG2a levels and CD8 + / CD4 + IFN-g + T cell frequencies induced by the vaccine and prolonged the survival of mice post lethal infection by approximately 7 days (149). Furthermore, mIl-7/mIl-15 genes subcloned into an adenovirus were able to extend the protective efficacy of the M. tuberculosis subunit vaccine (LT70 and MH fusion protein) by augmenting M. tuberculosis-specific central memory-like T cell responses (167). When mIl-7/mIl-2 were coadministered with the ovalbumin (OVA) DNA vaccine, mIL-7 and mIL-2 mutually improved its immunogenicity by upregulating the specific antibody titer, IFN-g production, and T cell proliferation (168).…”