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Updated: Jun 18, 2026
Protective Efficacy and Pulmonary Immune Response Following Subcutaneous and Intranasal BCG Administration in Mice
Published on: September 19, 2016
Immunogenicity and Protective Effects of an Ag85B Tuberculosis Subunit Vaccine Formulated with Synthetic TLR4
Soo-Min Kim1,2, Jin-Seung Yun1, EunJung Shin3
1Division of Infectious Disease Vaccine Research, Center for Vaccine Research, National Institute of Health, Korea Disease Control and Prevention Agency, 212 Osongsaengmyeong 2-ro, Osong-eup, Heungdeok-gu, Cheongju 28160, Republic of Korea.
Background/Objectives:
Tuberculosis (TB) remains a major global health challenge, and the Bacillus Calmette-Guérin (BCG) vaccine has limited efficacy against adult pulmonary disease. Protein subunit vaccines are a promising alternative but require strong adjuvants to induce cell-mediated immunity. Synthetic agonists targeting toll-like receptor 4 (TLR4) and stimulators of interferon genes (STINGs) have emerged as effective immunostimulants. Therefore, we aimed to evaluate the immunogenicity and protective efficacy of Ag85B-based subunit vaccines formulated with synthetic TLR4 and STING agonists in a BCG-boosted mouse model.
Methods:
Three synthetic adjuvants-QTP709-1, QTP709-3, and QTP701-were formulated as oil-in-water emulsions containing distinct surfactant and immunostimulant components. The potential of vaccine formulations to activate dendritic cells (DCs) and elicit Ag85B-specific immune responses, including IgG subclass levels, interferon-γ (IFN-γ) enzyme-linked immunosorbent spots, and polyfunctional T-cell responses, was assessed by flow cytometry. Protective efficacy was evaluated based on pulmonary bacterial burden and histopathology following Mycobacterium tuberculosis (M. tb) Erdman challenge.
Results:
All formulations promoted DC maturation and enhanced antigen-specific immune responses. Each adjuvant elicited strong Ag85B-specific humoral immunity, increased IFN-γ secretion, and polyfunctional CD4+ and CD8+ T cells co-producing IFN-γ, TNF-α, and interleukin-2. Among them, QTP709-1 was associated with increased levels of chemokine receptor 5-associated chemokines and showed a trend toward reduced lung bacterial burden and histopathological inflammation following M. tb challenge.
Conclusions:
Synthetic TLR4 and STING agonists were associated with enhanced immunogenicity of TB subunit vaccines and showed evidence of protective potential, with TLR4-based formulations exhibiting more pronounced immunological responses. QTP709-1 exhibited strong immunostimulatory and protective effects, supporting its potential as a candidate adjuvant for next-generation TB vaccines.
