MetE: a promising protective antigen for tuberculosis vaccine development

Salem Salman Almujri; Elena Stylianou; Annalisa Nicastri; Iman Satti; Marcellus Korompis; Shuailin Li; Christopher J. De Voss; Marco Polo Peralta Alvarez; Rachel Tanner; Paulo J.G. Bettencourt; Nicola Ternette; Helen McShane

doi:10.3389/fimmu.2025.1593263

MetE: a promising protective antigen for tuberculosis vaccine development

Salem Salman Almujri (Lead / Corresponding author)
, Elena Stylianou
, Annalisa Nicastri
, Iman Satti
, Marcellus Korompis
, Shuailin Li
, Christopher J. De Voss
, Marco Polo Peralta Alvarez
, Rachel Tanner
, Paulo J.G. Bettencourt
, Nicola Ternette
, Helen McShane (Lead / Corresponding author)

Cell Signalling and Immunology

Research output: Contribution to journal › Article › peer-review

2 Citations (Scopus)

68 Downloads (Pure)

Abstract

Introduction: Tuberculosis (TB), caused by Mycobacterium tuberculosis (MTB), remains a significant global health concern. The existing vaccine, Bacillus Calmette-Guérin (BCG), provides inconsistent protection, highlighting the pressing need for a more effective vaccine. We aimed to identify novel MTB antigens and assess their protective efficacy as TB vaccine candidates. Methods: Using immunopeptidomics, we identified 64 and 80 unique mycobacterial antigens derived from BCG and MTB, respectively. We prioritised antigens based on HLA allele coverage through an immunoinformatics approach. Results: The candidates, hisD, metE, and mmpL12, delivered as DNA vaccines, were evaluated for efficacy in mice using the ex vivo Mycobacterial Growth Inhibition Assay (MGIA) and metE was identified as a promising candidate. In vivo murine MTB challenge experiments confirmed the protective efficacy conferred by metE when formulated as recombinant protein with AS01™ or AddaS03™ adjuvants, compared to the naïve group. The immunogenic profiles of metE formulated in the two different adjuvants differed, with metE-AS01™ inducing antigen-specific IFN-γ, TNF-α, IL-2, IL-17, IgG1 and IgG2a-c, while metE-AddaS03™ induced TNF-α, IL-2, IL-17, IL-4, IgM, IgG1, IgG2b. Conclusion: Our findings highlight metE as a promising protective antigen for future TB vaccine development.

Original language	English
Article number	1593263
Number of pages	16
Journal	Frontiers in Immunology
Volume	16
DOIs	https://doi.org/10.3389/fimmu.2025.1593263
Publication status	Published - 21 Jul 2025

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

antigen discovery
HLA/MHC
immunoinformatics
immunopeptidomics
mass spectrometry
mycobacterium tuberculosis
tuberculosis
vaccines

ASJC Scopus subject areas

Immunology and Allergy
Immunology

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10.3389/fimmu.2025.1593263Licence: CC BY

Final published version
© 2025 Almujri, Stylianou, Nicastri, Satti, Korompis, Li, De Voss, Polo Peralta Alvarez, Tanner, Bettencourt, Ternette and McShane. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms
Final published version, 3.19 MBLicence: CC BY

Cite this

@article{6cdcfb91ff724daba37681322d3e07ec,

title = "MetE: a promising protective antigen for tuberculosis vaccine development",

abstract = "Introduction: Tuberculosis (TB), caused by Mycobacterium tuberculosis (MTB), remains a significant global health concern. The existing vaccine, Bacillus Calmette-Gu{\'e}rin (BCG), provides inconsistent protection, highlighting the pressing need for a more effective vaccine. We aimed to identify novel MTB antigens and assess their protective efficacy as TB vaccine candidates. Methods: Using immunopeptidomics, we identified 64 and 80 unique mycobacterial antigens derived from BCG and MTB, respectively. We prioritised antigens based on HLA allele coverage through an immunoinformatics approach. Results: The candidates, hisD, metE, and mmpL12, delivered as DNA vaccines, were evaluated for efficacy in mice using the ex vivo Mycobacterial Growth Inhibition Assay (MGIA) and metE was identified as a promising candidate. In vivo murine MTB challenge experiments confirmed the protective efficacy conferred by metE when formulated as recombinant protein with AS01{\texttrademark} or AddaS03{\texttrademark} adjuvants, compared to the na{\"i}ve group. The immunogenic profiles of metE formulated in the two different adjuvants differed, with metE-AS01{\texttrademark} inducing antigen-specific IFN-γ, TNF-α, IL-2, IL-17, IgG1 and IgG2a-c, while metE-AddaS03{\texttrademark} induced TNF-α, IL-2, IL-17, IL-4, IgM, IgG1, IgG2b. Conclusion: Our findings highlight metE as a promising protective antigen for future TB vaccine development.",

keywords = "antigen discovery, HLA/MHC, immunoinformatics, immunopeptidomics, mass spectrometry, mycobacterium tuberculosis, tuberculosis, vaccines",

author = "Almujri, \{Salem Salman\} and Elena Stylianou and Annalisa Nicastri and Iman Satti and Marcellus Korompis and Shuailin Li and \{De Voss\}, \{Christopher J.\} and \{Polo Peralta Alvarez\}, Marco and Rachel Tanner and Bettencourt, \{Paulo J.G.\} and Nicola Ternette and Helen McShane",

note = "Publisher Copyright: Copyright {\textcopyright} 2025 Almujri, Stylianou, Nicastri, Satti, Korompis, Li, De Voss, Polo Peralta Alvarez, Tanner, Bettencourt, Ternette and McShane.",

year = "2025",

month = jul,

day = "21",

doi = "10.3389/fimmu.2025.1593263",

language = "English",

volume = "16",

journal = "Frontiers in Immunology",

issn = "1664-3224",

publisher = "Frontiers Media S.A.",

}

TY - JOUR

T1 - MetE

T2 - a promising protective antigen for tuberculosis vaccine development

AU - Almujri, Salem Salman

AU - Stylianou, Elena

AU - Nicastri, Annalisa

AU - Satti, Iman

AU - Korompis, Marcellus

AU - Li, Shuailin

AU - De Voss, Christopher J.

AU - Polo Peralta Alvarez, Marco

AU - Tanner, Rachel

AU - Bettencourt, Paulo J.G.

AU - Ternette, Nicola

AU - McShane, Helen

PY - 2025/7/21

Y1 - 2025/7/21

N2 - Introduction: Tuberculosis (TB), caused by Mycobacterium tuberculosis (MTB), remains a significant global health concern. The existing vaccine, Bacillus Calmette-Guérin (BCG), provides inconsistent protection, highlighting the pressing need for a more effective vaccine. We aimed to identify novel MTB antigens and assess their protective efficacy as TB vaccine candidates. Methods: Using immunopeptidomics, we identified 64 and 80 unique mycobacterial antigens derived from BCG and MTB, respectively. We prioritised antigens based on HLA allele coverage through an immunoinformatics approach. Results: The candidates, hisD, metE, and mmpL12, delivered as DNA vaccines, were evaluated for efficacy in mice using the ex vivo Mycobacterial Growth Inhibition Assay (MGIA) and metE was identified as a promising candidate. In vivo murine MTB challenge experiments confirmed the protective efficacy conferred by metE when formulated as recombinant protein with AS01™ or AddaS03™ adjuvants, compared to the naïve group. The immunogenic profiles of metE formulated in the two different adjuvants differed, with metE-AS01™ inducing antigen-specific IFN-γ, TNF-α, IL-2, IL-17, IgG1 and IgG2a-c, while metE-AddaS03™ induced TNF-α, IL-2, IL-17, IL-4, IgM, IgG1, IgG2b. Conclusion: Our findings highlight metE as a promising protective antigen for future TB vaccine development.

AB - Introduction: Tuberculosis (TB), caused by Mycobacterium tuberculosis (MTB), remains a significant global health concern. The existing vaccine, Bacillus Calmette-Guérin (BCG), provides inconsistent protection, highlighting the pressing need for a more effective vaccine. We aimed to identify novel MTB antigens and assess their protective efficacy as TB vaccine candidates. Methods: Using immunopeptidomics, we identified 64 and 80 unique mycobacterial antigens derived from BCG and MTB, respectively. We prioritised antigens based on HLA allele coverage through an immunoinformatics approach. Results: The candidates, hisD, metE, and mmpL12, delivered as DNA vaccines, were evaluated for efficacy in mice using the ex vivo Mycobacterial Growth Inhibition Assay (MGIA) and metE was identified as a promising candidate. In vivo murine MTB challenge experiments confirmed the protective efficacy conferred by metE when formulated as recombinant protein with AS01™ or AddaS03™ adjuvants, compared to the naïve group. The immunogenic profiles of metE formulated in the two different adjuvants differed, with metE-AS01™ inducing antigen-specific IFN-γ, TNF-α, IL-2, IL-17, IgG1 and IgG2a-c, while metE-AddaS03™ induced TNF-α, IL-2, IL-17, IL-4, IgM, IgG1, IgG2b. Conclusion: Our findings highlight metE as a promising protective antigen for future TB vaccine development.

KW - antigen discovery

KW - HLA/MHC

KW - immunoinformatics

KW - immunopeptidomics

KW - mass spectrometry

KW - mycobacterium tuberculosis

KW - tuberculosis

KW - vaccines

UR - https://www.scopus.com/pages/publications/105012460584

U2 - 10.3389/fimmu.2025.1593263

DO - 10.3389/fimmu.2025.1593263

M3 - Article

C2 - 40761798

AN - SCOPUS:105012460584

SN - 1664-3224

VL - 16

JO - Frontiers in Immunology

JF - Frontiers in Immunology

M1 - 1593263

ER -

MetE: a promising protective antigen for tuberculosis vaccine development

Abstract

UN SDGs

Keywords

ASJC Scopus subject areas

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