Exercise training confers broad health benefits, yet molecular regulators of skeletal muscle adaptation, particularly sex-specific mechanisms, remain incompletely understood. Integrating new and previously published multi-omics data from the molecular transducers of physical activity consortium (MoTrPAC), we characterized metabolomic, epigenomic, transcriptomic, proteomic, and post-translational modification (PTM) responses to 1-8 weeks of endurance exercise training in male and female rat gastrocnemius. While transcriptomic and proteomic responses were largely sex-concordant, there were distinct sex-specific training-induced PTM signatures, particularly in the redox proteome. Females exhibited decreased mitochondrial protein cysteine oxidation alongside increased oxidation of glycolytic proteins relative to males, suggesting sex-biased subcellular reactive oxygen species (ROS) dynamics. Multi-omic factor analysis (MOFA) identified coordinated sex-concordant molecular programs and further supported female-specific mechanisms of redox buffering with training. Together, these findings indicate that sex-specific skeletal muscle exercise adaptations are particularly evident at the PTM level in rats, and identify future avenues for precision exercise health and medicine.
Gina M. Many, C. Jin, N. Day et al.· Cell Reports· 0 citations
ABSTRACT The emergence of the SARS-CoV-2 Omicron BA.2.86 subvariant, a lineage derived from the BA.2 strain, led to the 2024–2025 COVID-19 vaccine update to include KP.2 or related JN.1-lineage spike antigens. We evaluated the magnitude, breadth, and durability of humoral immune responses following a single KP.2 vaccine dose in a longitudinal cohort of 21 individuals up to 6 months. KP.2 vaccination increased spike-specific binding and neutralizing antibodies against the ancestral WA.1 strain, as well as against the BA.5, XBB.1.5, and KP.2 variants. Power-law modeling estimated half-lives for WA.1- and KP.2-specific IgG responses at 770 and 248 days, respectively. Additionally, the KP.2 dose increased IgG1 and IgG4 subclasses more than IgG2 and IgG3 responses to both spike proteins. Serum-depletion experiments using WA.1 or KP.2 proteins demonstrated that most vaccine-elicited antibodies were cross-reactive. Consequently, KP.2 vaccine-induced antibodies retained broad neutralizing activity against recently circulating Omicron subvariants (BA.2.86, KP.3.1.1, XEC, LP.8.1, LF.7, XFG.3.12, PQ.1, BA.3.2.1, and RE.2). Using a live virus neutralization assay, XFG.3.12 showed the greatest reduction in neutralizing titers relative to KP.2 (4.2-fold). In a small subset, an LP.8.1 vaccine dose increased neutralizing activity against the matched variant while maintaining WA.1 and KP.2 cross-reactivity, but only modestly increased antibodies to divergent variants BA.3.2.1 and RE.2. Ultimately, these data indicate the KP.2 mRNA vaccine generates durable, cross-reactive responses against current Omicron subvariants. However, ongoing spike evolution impacts the neutralization of emerging lineages, highlighting the need for continued viral monitoring and timely vaccine updates. IMPORTANCE SARS-CoV-2 continues to evolve, raising ongoing concerns about how well updated vaccines protect against emerging variants. This study evaluates antibody responses after a KP.2 spike mRNA vaccine dose. It shows that a single dose induces durable and broadly cross-reactive immunity against both earlier strains and recently circulating Omicron subvariants. Despite this breadth, reduced neutralizing activity against certain emerging variants indicates that ongoing antigenic changes can impact vaccine-induced antibody effectiveness. These findings provide insight into how current vaccines perform over time and highlight the need to track viral evolution and update vaccine antigens to maintain broad protection against severe disease, hospitalization, and death. SARS-CoV-2 continues to evolve, raising ongoing concerns about how well updated vaccines protect against emerging variants. This study evaluates antibody responses after a KP.2 spike mRNA vaccine dose. It shows that a single dose induces durable and broadly cross-reactive immunity against both earlier strains and recently circulating Omicron subvariants. Despite this breadth, reduced neutralizing activity against certain emerging variants indicates that ongoing antigenic changes can impact vaccine-induced antibody effectiveness. These findings provide insight into how current vaccines perform over time and highlight the need to track viral evolution and update vaccine antigens to maintain broad protection against severe disease, hospitalization, and death.
Sanjeev Kumar, Lilin Lai, M. Ellis et al.· Journal of Virology· 0 citations