PMID- 36405961
OWN - NLM
STAT- MEDLINE
DCOM- 20221122
LR  - 20221128
IS  - 2235-2988 (Electronic)
IS  - 2235-2988 (Linking)
VI  - 12
DP  - 2022
TI  - Evaluation of the consistence between the results of immunoinformatics 
      predictions and real-world animal experiments of a new tuberculosis vaccine 
      MP3RT.
PG  - 1047306
LID - 10.3389/fcimb.2022.1047306 [doi]
LID - 1047306
AB  - BACKGROUND: Our previous study developed a novel peptide-based vaccine, MP3RT, to 
      fight against tuberculosis (TB) infection in a mouse model. However, the 
      consistency between the immunoinformatics predictions and the results of 
      real-world animal experiments on the MP3RT vaccine remains unclear. METHOD: In 
      this study, we predicted the antigenicity, immunogenicity, physicochemical 
      parameters, secondary structure, and tertiary structure of MP3RT using 
      bioinformatics technologies. The immune response properties of the MP3RT vaccine 
      were then predicted using the C-ImmSim server. Finally, humanized mice were used 
      to verify the characteristics of the humoral and cellular immune responses 
      induced by the MP3RT vaccine. RESULTS: MP3RT is a non-toxic and non-allergenic 
      vaccine with an antigenicity index of 0.88 and an immunogenicity index of 0.61, 
      respectively. Our results showed that the MP3RT vaccine contained 53.36% alpha-helix 
      in the secondary structure, and the favored region accounted for 98.22% in the 
      optimized tertiary structure. The binding affinities of the MP3RT vaccine to the 
      human leukocyte antigen (HLA)-DRB1*01:01 allele, toll-like receptor-2 (TLR-2), 
      and TLR-4 receptors were -1234.1 kcal/mol, -1066.4 kcal/mol, and -1250.4 
      kcal/mol, respectively. The results of the C-ImmSim server showed that the MP3RT 
      vaccine could stimulate T and B cells to produce immune responses, such as high 
      levels of IgM and IgG antibodies, IFN-gamma, TNF-alpha, and IL-2 cytokines. Results from 
      real-world animal experiments showed that the MP3RT vaccine could stimulate the 
      humanized mice to produce high levels of IgG and IgG2a antibodies and IFN-gamma(+) T 
      lymphocytes. Furthermore, the levels of IFN-gamma, IL-2, and IL-6 cytokines in mice 
      immunized with the MP3RT vaccine were significantly higher than those in the 
      control group. CONCLUSION: MP3RT is a highly antigenic and immunogenic potential 
      vaccine that can effectively induce Th1-type immune responses in silico analysis 
      and animal experiments. This study lays the foundation for evaluating the value 
      of computational tools and immunoinformatic techniques in reverse vaccinology 
      research.
CI  - Copyright (c) 2022 Cheng, Xue, Wang, Jia, Wang and Gong.
FAU - Cheng, Peng
AU  - Cheng P
AD  - Tuberculosis Prevention and Control Key Laboratory/Beijing Key Laboratory of New 
      Techniques of Tuberculosis Diagnosis and Treatment, Senior Department of 
      Tuberculosis, The 8th Medical Center of PLA General Hospital, Beijing, China.
AD  - Hebei North University, Zhangjiakou, Hebei, 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 8th Medical Center of PLA General Hospital, Beijing, 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 8th Medical Center of PLA General Hospital, Beijing, China.
FAU - Jia, Zaixing
AU  - Jia Z
AD  - Tuberculosis Prevention and Control Key Laboratory/Beijing Key Laboratory of New 
      Techniques of Tuberculosis Diagnosis and Treatment, Senior Department of 
      Tuberculosis, The 8th Medical Center of PLA General Hospital, Beijing, China.
AD  - Cangzhou Hospital of Integrated Traditional Chinese and Western Medicine, 
      Cangzhou, Hebei, China.
FAU - Wang, Liang
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 8th Medical Center of PLA General Hospital, Beijing, China.
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 8th Medical Center of PLA General Hospital, Beijing, China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20221102
PL  - Switzerland
TA  - Front Cell Infect Microbiol
JT  - Frontiers in cellular and infection microbiology
JID - 101585359
RN  - 0 (Tuberculosis Vaccines)
RN  - 0 (Interleukin-2)
RN  - 0 (Vaccines, Subunit)
RN  - 0 (Cytokines)
RN  - 0 (Immunoglobulin G)
SB  - IM
MH  - Humans
MH  - Mice
MH  - Animals
MH  - *Tuberculosis Vaccines
MH  - *Animal Experimentation
MH  - Interleukin-2
MH  - Vaccines, Subunit
MH  - Cytokines
MH  - Immunoglobulin G
MH  - *Tuberculosis/prevention & control
PMC - PMC9666678
OTO - NOTNLM
OT  - MP3RT
OT  - computational tools
OT  - immune responses
OT  - immunoinformatics
OT  - tuberculosis (TB)
OT  - vaccine
COIS- The authors declare that the research was conducted in the absence of any 
      commercial or financial relationships that could be construed as a potential 
      conflict of interest.
EDAT- 2022/11/22 06:00
MHDA- 2022/11/23 06:00
PMCR- 2022/01/01
CRDT- 2022/11/21 04:08
PHST- 2022/09/18 00:00 [received]
PHST- 2022/10/17 00:00 [accepted]
PHST- 2022/11/21 04:08 [entrez]
PHST- 2022/11/22 06:00 [pubmed]
PHST- 2022/11/23 06:00 [medline]
PHST- 2022/01/01 00:00 [pmc-release]
AID - 10.3389/fcimb.2022.1047306 [doi]
PST - epublish
SO  - Front Cell Infect Microbiol. 2022 Nov 2;12:1047306. doi: 
      10.3389/fcimb.2022.1047306. eCollection 2022.