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<p>Tuberculosis (TB) remains a major global health threat, underscoring the need for vaccines that surpass BCG efficacy. We developed QTAP-R, a novel mRNA–lipid nanoparticle (LNP) vaccine encoding Ag85B, Hsp70, and ESAT-6, to enhance immunity against <i>Mycobacterium tuberculosis</i>. QTAP efficiently encapsulated and delivered mRNA with high transfection efficiency and low cytotoxicity. In C57BL/6 mice, QTAP-R induced strong antigen-specific IgG and T-cell responses, including elevated CD4⁺ and CD8⁺ activation and increased polyfunctional cytokines (IFN-γ, TNF-α, IL-2, IL-17A). When combined with BCG (BCG + QTAP-R), the vaccine elicited enhanced immune memory, reduced bacterial burden in lungs and spleen, and minimized lung pathology following <i>M. tuberculosis</i> challenge. Subcutaneous QTAP-R (QTAP-SQ) provided partial protection under high-dose challenge, outperforming intranasal delivery. Transcriptomic profiling revealed upregulation of inflammatory cytokines (IL-1, IL-6, IL-12) and chemokines (CCL3, CCL4, CXCL9, CXCL10), indicating enhanced immune recruitment and activation. CD4⁺ T-cell depletion abolished protection, confirming their critical role in QTAP-R–mediated immunity. Overall, QTAP-R demonstrates potent immunogenicity and synergistic efficacy with BCG, positioning it as a promising mRNA-based TB vaccine candidate.</p>

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Superior protection against tuberculosis using heterologous mRNA nanoadjuvant vaccines

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年5月2日

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  • Bubacarr J. B. Touray,
  • Alieu K. Faburay,
  • Fakry F. Mohamed,
  • Sherein S. Abdelgayed,
  • Adel M. Talaat

摘要

Tuberculosis (TB) remains a major global health threat, underscoring the need for vaccines that surpass BCG efficacy. We developed QTAP-R, a novel mRNA–lipid nanoparticle (LNP) vaccine encoding Ag85B, Hsp70, and ESAT-6, to enhance immunity against Mycobacterium tuberculosis. QTAP efficiently encapsulated and delivered mRNA with high transfection efficiency and low cytotoxicity. In C57BL/6 mice, QTAP-R induced strong antigen-specific IgG and T-cell responses, including elevated CD4⁺ and CD8⁺ activation and increased polyfunctional cytokines (IFN-γ, TNF-α, IL-2, IL-17A). When combined with BCG (BCG + QTAP-R), the vaccine elicited enhanced immune memory, reduced bacterial burden in lungs and spleen, and minimized lung pathology following M. tuberculosis challenge. Subcutaneous QTAP-R (QTAP-SQ) provided partial protection under high-dose challenge, outperforming intranasal delivery. Transcriptomic profiling revealed upregulation of inflammatory cytokines (IL-1, IL-6, IL-12) and chemokines (CCL3, CCL4, CXCL9, CXCL10), indicating enhanced immune recruitment and activation. CD4⁺ T-cell depletion abolished protection, confirming their critical role in QTAP-R–mediated immunity. Overall, QTAP-R demonstrates potent immunogenicity and synergistic efficacy with BCG, positioning it as a promising mRNA-based TB vaccine candidate.