Id3 and Bcl6 Promote the Development of Long-Term Immune Memory Induced by Tuberculosis Subunit Vaccine

Abstract

Long-lived memory cell formation and maintenance are usually regulated by cytokines and transcriptional factors. Adjuvant effects of IL-7 have been studied in the vaccines of influenza and other pathogens. However, few studies investigated the adjuvant effects of cytokines and transcriptional factors in prolonging the immune memory induced by a tuberculosis (TB) subunit vaccine. To address this research gap, mice were treated with the Mycobacterium tuberculosis (M. tuberculosis) subunit vaccine Mtb10.4-HspX (MH) plus ESAT6-Ag85B-MPT64<190–198>-Mtb8.4-Rv2626c (LT70), together with adeno-associated virus-mediated IL-7 or lentivirus-mediated transcriptional factor Id3, Bcl6, Bach2, and Blimp1 at 0, 2, and 4 weeks, respectively. Immune responses induced by the vaccine were examined at 25 weeks after last immunization. The results showed that adeno-associated virus-mediated IL-7 allowed the TB subunit vaccine to induce the formation of long-lived memory T cells. Meanwhile, IL-7 increased the expression of Id3, Bcl6, and bach2—the three key transcription factors for the generation of long-lived memory T cells. The adjuvant effects of transcriptional factors, together with TB fusion protein MH/LT70 vaccination, showed that both Bcl6 and Id3 increased the production of antigen-specific antibodies and long-lived memory T cells, characterized by high proliferative potential of antigen-specific CD4+ and CD8+ T cells, and IFN-γ secretion in CD4+ and CD8+ T cells, respectively, after re-exposure to the same antigen. Overall, our study suggests that IL-7 and transcriptional factors Id3 and Bcl6 help the TB subunit vaccine to induce long-term immune memory, which contributes to providing immune protection against M. tuberculosis infection.

IL-7 in SARS-CoV-2 Infection and as a Potential Vaccine Adjuvant

“…Another study confirmed that administration of IL-7 induced higher levels of transcription factors including Id3, bcl6 and bach2, and increased antibody and memory T cells when mice received adeno-associated virus-delivered IL-7 (rAAV-IL-7) with a tuberculosis subunit vaccine (43). Non-traumatic administration of recombinant glycosylated simian IL-7 (rs-IL-7gly) into the vaginal mucosa triggered overexpression of chemokines and cytokines and enhanced strong antibody responses in macaques (44).…”

Optimizing the Boosting Schedule of Subunit Vaccines Consisting of BCG and “Non-BCG” Antigens to Induce Long-Term Immune Memory

“…At 28 weeks after vaccine immunization, the antigen-specific effector memory T cells would fade away, so the vaccine-induced long-lived memory T cells were analyzed ( 41 ). The immune responses following antigen stimulation to monitor the number and function of vaccine-induced long-lived memory T cells indirectly by two methods as follow ( 25 , 41 ).…”

“…Our previous experiment showed that at 25 weeks following subunit vaccine immunization, once antigen stimulation could not induce cytokines production ( 41 ), which suggests that T EM cells wane at that time ( 42 ). Therefore, at 28 weeks after vaccination only long-lived memory T cells (T SCM and T CM ) exist.…”

“…Upon antigen stimulation antigen-specific T SCM and T CM cells proliferate and differentiate into T EM and T eff cells, and then produce cytokine IFN-γ ( 32 , 43 , 44 ). Based on the principle, in our previous studies we detected the role long-lived memory T cells through analyzing IFN-γ production following stimulation with same antigen twice every 9 days ( 25 , 41 ).…”

Adjuvants and Antigen-Delivery Systems for Subunit Vaccines against Tuberculosis

“…In this Special Issue, the results of the adjuvant effects of the cytokine IL-7and transcriptional factors (Id3, Bcl6, Bach2, and Blimp1) in increasing the duration of the immune memory induced by tuberculosis subunit vaccines was studied in mice by Han et al [ 23 ]. Groups of mice were immunized three times at two-week intervals with the M. tuberculosis subunit vaccine Mtb10.4-HspX (MH) plus ESAT6-Ag85B-MPT64 <190–198> -Mtb8.4-Rv2626c (LT70), together with adeno-associated virus-mediated IL-7 or lentivirus-mediated transcriptional factor Id3, Bcl6, Bach2, and Blimp1.…”