Immunoglobulin G profiles in different forms of periodontitis.
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Zhou Ting, Zhang Bingyu, Lu Yiwen, Chen Jiajie, Zang Chengxi, Li Haoyang, Elia Josephine, Prasad Raghuram, Arnold Jonathan, Avedissian Sean N, Bailey L Charles, Becich Michael J, Bensken Wyatt P, Bisyuk Yuriy, Bunnell H Timothy, Castro Leah, Chrischilles Elizabeth A, Christakis Dimitri A, Cowell Lindsay G, Cummins Mollie R, Fernandez Soledad, Fort Daniel, Gonzalez Sandy, Herring Sharon J, Hornig Mady, Hwang Wenke, Jain Nita, Jones W Schuyler, Kaelber David C, Kelleher Kelly, Kenney Rachel, Leikauf John E, Letts Rebecca, Liu Mei, Martinez Aaron Thomas, May Heidi T, Mosa Abu Saleh Mohammad, Pajor Nathan M, Rao Suchitra, Salisbury Amy L, Suresh Srinivasan, Swaminathan Aparna C, Taylor Bradley W, Thomas Neena Anne, Williams David A, Witvliet Margot Gage, Kaushal Rainu, Wang Fei, Forrest Christopher B, Chen Yong
Аннотация
UNLABELLED: Tuberculosis (TB), the biggest cause of death from any known infectious disease, has been a problem for the world's health system for many years. The only approved vaccine is BCG and now a number of vaccines are undergoing clinical trials. The newly recognised mRNA vaccines can provide a good alternative to the traditional vaccine. Therefore, the goal of this work is to use computational techniques to build a multi-stage tuberculosis mRNA vaccine. Nine multistage-expressing Mycobacterium tuberculosis (Mtb) proteins that have been linked to cell entry, pathogenesis, and dormancy regulon were used. Eighteen promiscuous, proinflammatory, non-toxic antigenic epitopes that bound to both MHC classes (I and II) were chosen from nine proteins. Co-translational structural components (5'm7G cap, UTRs, Kozak sequence, Poly A tail) were incorporated into the design of the mRNA vaccine, which was predicted to be stable. Additionally, molecular docking reveals the vaccine candidate's interaction with TLR2 and TLR4 immunological receptors by establishing a Leucine-Rich-Repeats (LRR) specific interface. Molecular dynamics (MD) simulations were also performed to evaluate the structural stability and dynamical behaviour of the vaccine candidate in complex with TLR2 and TLR4. Following the simulations, binding free energy calculations were conducted using the Molecular Mechanics/Poisson-Boltzmann Surface Area (MM/PBSA) method, which indicated stable thermodynamic binding of the vaccine candidate with both the receptors. Immune simulation tests using C-Immsim predicted that the translated vaccine construct was immunogenic and showed population coverage of 99.98%. Overall, it was anticipated that this multi-stage expressing mRNA vaccine would be highly immunogenic, stable, safe, and antigenic. Our approach to develop an immunoinformatics-based mRNA vaccine appears promising against tuberculosis; nonetheless, experimental confirmation is required.
SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s40203-026-00675-8.