PMID- 36460380 OWN - NLM STAT- MEDLINE DCOM- 20221206 LR - 20221206 IS - 0019-5707 (Print) IS - 0019-5707 (Linking) VI - 69 IP - 4 DP - 2022 Oct TI - A peptide-based vaccine ACP derived from antigens of Mycobacterium tuberculosis induced Th1 response but failed to enhance the protective efficacy of BCG in mice. PG - 482-495 LID - S0019-5707(21)00158-X [pii] LID - 10.1016/j.ijtb.2021.08.016 [doi] AB - BACKGROUND: Tuberculosis (TB) is a global infectious disease, but there is no ideal vaccine against TB except the Bacille Calmette-Guerin (BCG) vaccine. METHODS: Herein, 25 candidate peptides were predicted from four antigens of Mycobacterium tuberculosis based on their high-affinity binding capacity for the human leukocyte antigen (HLA) DRB1 *0101. Three T-helper 1 (Th1) immunodominant peptides (Ag85B(12-26), CFP21(12-26), and PPE18(149-163)) were identified by ELISPOT assays in the humanized C57BL/6 mice. They resulted in a novel Th1 peptide-based vaccine ACP named by the first letter of the three peptides. In addition, the protective efficacy was evaluated in humanized or wild-type C57BL/6 mice and the humoral and cellular immune responses were confirmed in vitro. RESULTS: Compared with the PBS group, the ACP vaccinated mice showed slight decreases in colony-forming units (CFUs) and pathological lesions. However, when using it as a booster, the ACP vaccine did not significantly enhance the protective efficacy of BCG in humanized or wild-type mice. Interestingly, we found that ACP vaccination significantly increased the number of interferon-gamma positive (IFN-gamma(+)) T lymphocytes and the levels of IFN-gamma cytokines as well as antibodies. Furthermore, the IL-2 level was significantly higher in humanized mice prime-boosted with BCG and ACP. CONCLUSIONS: Our results suggested that ACP vaccination could stimulate higher levels of cytokines and antibodies but failed to improve the protective efficacy of BCG in mice, indicating that the secretion level of IFN-gamma may not be positively correlated with the protection efficiency of the vaccine. These findings provided important information on the feasibility of a peptide vaccine as a booster for enhancing the protective efficacy of BCG. CI - Copyright (c) 2021 Tuberculosis Association of India. Published by Elsevier B.V. All rights reserved. FAU - Gong, Wenping AU - Gong W AD - Tuberculosis Prevention and Control Key Laboratory/Beijing Key Laboratory of New Techniques of Tuberculosis Diagnosis and Treatment, Senior Department of Tuberculosis, The Eighth Medical Center of PLA General Hospital, Beijing, 100091, China. FAU - Liang, Yan AU - Liang Y AD - Tuberculosis Prevention and Control Key Laboratory/Beijing Key Laboratory of New Techniques of Tuberculosis Diagnosis and Treatment, Senior Department of Tuberculosis, The Eighth Medical Center of PLA General Hospital, Beijing, 100091, China. FAU - Mi, Jie AU - Mi J AD - Tuberculosis Prevention and Control Key Laboratory/Beijing Key Laboratory of New Techniques of Tuberculosis Diagnosis and Treatment, Senior Department of Tuberculosis, The Eighth Medical Center of PLA General Hospital, Beijing, 100091, China. FAU - Xue, Yong AU - Xue Y AD - Tuberculosis Prevention and Control Key Laboratory/Beijing Key Laboratory of New Techniques of Tuberculosis Diagnosis and Treatment, Senior Department of Tuberculosis, The Eighth Medical Center of PLA General Hospital, Beijing, 100091, China. FAU - Wang, Jie AU - Wang J AD - Tuberculosis Prevention and Control Key Laboratory/Beijing Key Laboratory of New Techniques of Tuberculosis Diagnosis and Treatment, Senior Department of Tuberculosis, The Eighth Medical Center of PLA General Hospital, Beijing, 100091, China. FAU - Wang, Lan AU - Wang L AD - Tuberculosis Prevention and Control Key Laboratory/Beijing Key Laboratory of New Techniques of Tuberculosis Diagnosis and Treatment, Senior Department of Tuberculosis, The Eighth Medical Center of PLA General Hospital, Beijing, 100091, China. FAU - Zhou, Yusen AU - Zhou Y AD - State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, 100071, China. FAU - Sun, Shihui AU - Sun S AD - State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, 100071, China. FAU - Wu, Xueqiong AU - Wu X AD - Tuberculosis Prevention and Control Key Laboratory/Beijing Key Laboratory of New Techniques of Tuberculosis Diagnosis and Treatment, Senior Department of Tuberculosis, The Eighth Medical Center of PLA General Hospital, Beijing, 100091, China. Electronic address: xueqiongwu@139.com. LA - eng PT - Journal Article DEP - 20210818 PL - India TA - Indian J Tuberc JT - The Indian journal of tuberculosis JID - 0373027 RN - 0 (BCG Vaccine) RN - 0 (Vaccines, Subunit) RN - 82115-62-6 (Interferon-gamma) RN - 0 (Cytokines) SB - IM MH - Humans MH - Mice MH - Animals MH - *Mycobacterium tuberculosis MH - Mice, Inbred C57BL MH - BCG Vaccine MH - *Tuberculosis, Lymph Node MH - Vaccines, Subunit MH - Interferon-gamma MH - Cytokines OTO - NOTNLM OT - Bacille Calmette-Guerin (BCG) OT - Human MHC transgenic mice OT - Peptide OT - Tuberculosis OT - Vaccine COIS- Conflicts of interest The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results. EDAT- 2022/12/03 06:00 MHDA- 2022/12/07 06:00 CRDT- 2022/12/02 21:04 PHST- 2021/05/22 00:00 [received] PHST- 2021/07/31 00:00 [revised] PHST- 2021/08/10 00:00 [accepted] PHST- 2022/12/02 21:04 [entrez] PHST- 2022/12/03 06:00 [pubmed] PHST- 2022/12/07 06:00 [medline] AID - S0019-5707(21)00158-X [pii] AID - 10.1016/j.ijtb.2021.08.016 [doi] PST - ppublish SO - Indian J Tuberc. 2022 Oct;69(4):482-495. doi: 10.1016/j.ijtb.2021.08.016. Epub 2021 Aug 18.