Indexed by: Journal paper

First Author: Ling Hao

Correspondence Author: Xionglin Fan

Co-author: Yaqi Wu, Yandi Zhang, Zijie Zhou, Qing Lei, Nadeem Ullah, Jo-Lewis Banga Ndzouboukou, Xiaosong Lin

Journal: Frontiers in immunology

Affiliation of Author(s): 华中科技大学

Discipline: Medicine

First-Level Discipline: Basic Medicine

Document Type: J

Volume: 11

Page Number: 575504

ISSN No.: 1664-3224

Key Words: Bacillus Calmette-Guerin; adjuvant; monophosphoryl lipid A; pattern-recognition receptor agonist; primary infection; subunit vaccine; trehalose-6,6’-dibehenate; tuberculosis.

DOI number: 10.3389/fimmu.2020.575504

Date of Publication: 2020-09-30

Impact Factor: 7.561

Teaching and Research Group: 华中科技大学基础医学院病原生物学医学微生物学

Abstract: Bacillus Calmette-Guerin (BCG) is the only licensed vaccine to prevent children from tuberculosis (TB), whereas it cannot provide effective protection for adults. Our previous work showed a novel vaccine candidate, liposomal adjuvant DMT emulsified with a multistage antigen CMFO, could protect mice against primary progressive TB, latency, and reactivation. To develop a more effective vaccine against adult TB, we aimed to further understand the role of pattern recognition receptor (PRR) agonists monophosphoryl lipid A (MPLA) and trehalose-6,6'-dibehenate (TDB) of the liposomal adjuvant DMT in the CMFO subunit vaccine-induced protection. Using C57BL/6 mouse models, the current study prepared different dimethyldioctadecylammonium (DDA)-based liposomal adjuvants with MPLA, TDB, or both (DMT), and then compared the immunogenicity and the protective efficacy among different liposomal adjuvanted CMFO subunit vaccines. Our study demonstrated that CMFO/DMT provided stronger and longer-lasting protective efficacy than the CMFO emulsified with adjuvants DDA or DDA/TDB. In addition, DDA/MPLA adjuvanted CMFO conferred a comparable protection in the lung as CMFO/DMT did. Higher levels of IFN-γ, IL-2, TNF-α, and IL-17A secreted by splenocytes were related with a more powerful and durable protection induced by CMFO/DMT through a putative synergistic effect of both MPLA and TDB via binding to TLR4 and Mincle. IL-2+ CD4+ T cells, especially IL-2+ CD4+ TCM cells, in the lung after infection were significantly associated with the vaccine-induced protection, whereas stronger IL-10 response and lower IL-2+ CD4+ T cells also contributed to the inferior protection of the DDA/TDB adjuvanted CMFO subunit vaccine. Given their crucial roles in vaccine-induced protection, combinational different PRR agonists in adjuvant formulation represent a promising strategy for the development of next-generation TB vaccine.

Note: 5) L.Hao, Y. Wu,Y. Zhang, etal. Combinational PRR Agonists in Liposomal Adjuvant Enhances Immunogenicity and Protective Efficacy in a Tuberculosis Subunit Vaccine. Frontiers in Immunology, 2020, 11:575504.

Links to published journals: https://www.frontiersin.org/articles/10.3389/fimmu.2020.575504/full