Junttila, I. S. | bioRxiv Science

bioRxiv2026

Multivalent mRNA tuberculosis vaccines protect against mycobacterial infection in zebrafish, mice and guinea pigs

Despite a century of BCG use, tuberculosis remains a leading cause of death from infectious diseases and more effective vaccines are urgently needed. Here we combined antigen discovery in zebrafish with mRNA vaccine technology to generate multivalent vaccine candidates, TUmRNA4, TUmRNA6 and TUmRNA9, encoding four, six, or nine Mycobacterium tuberculosis antigens, respectively. The vaccines were well tolerated, and induced robust antigen-specific cellular immune responses, including IFN{gamma} production and expansion of memory T-cell populations. In mice, TUmRNA4 and TUmRNA6 reduced pulmonary M. tuberculosis burden and lung pathology to levels comparable to BCG vaccination and TUmRNA6 enhanced BCG-mediated protection when used as a booster vaccine. In guinea pigs, TUmRNA9 reduced bacterial burden in the lungs, spleen, and lymph nodes and decreased pulmonary lesions. These findings demonstrate that protective antigens identified in zebrafish can be translated into effective multivalent mRNA vaccines and establish a framework for tuberculosis vaccine development across multiple preclinical models.

immunology↗

bioRxiv2024

Biological aging of different blood cell types

A biological age (BA) indicator is intended to capture detrimental age-related changes occurring with passing time. To date, the best-known and used BA indicators include DNA-methylation-based epigenetic ages (epigenetic clocks) and telomere length. The most common biological sample material for epidemiological aging studies is composed of different cell types, whole blood. We aimed to compare differences in BAs between blood cell types and assessed BA indicators cell type-specific associations with donors calendar age. Analysis on DNA methylation-based BA indicators including telomere length, methylation level at cg16867657 (a CpG-site in ELOVL2) and the Hannum, Horvath, DNAmPhenoAge and DunedinPACE epigenetic clocks was performed in 428 biological samples from 12 blood cell types. BA values were different (p<0.05) in the majority of pairwise comparisons between the cell types. Most cell types also displayed differences as compared to whole blood (p<0.05). Some of the observed differences persisted across blood donors calendar ages from 20 to 80 years (50-years-difference in DNAmPhenoAge between naive CD4+ T cells and monocytes), while others did not (up to four-fold difference in DunedinPACE values between monocytes and B cells). All BA indicators, except DunedinPACE, had mostly a very strong correlation with donors calendar age within a cell type. Our findings demonstrate that DNA methylation-based indicators of biological age exhibit cell type-specific characteristics, underscoring the importance of accounting for cell composition in related studies. Our results have implications for understanding the molecular mechanisms underlying epigenetic clocks and and provide guidance for utilizing them as indicators for success of aging interventions.

molecular biology↗