Whitehead, S. | Search bioRxiv

bioRxiv2024

Between-day reliability of local and global muscle-tendon unit assessments in female athletes whilst controlling for menstrual cycle phase

Measurements of muscle-tendon unit (MTU) function can be categorised into local (e.g. tendon strain) or global (e.g. jump height) assessments. Although menstrual cycle phase may be a key consideration when implementing these assessments in female athletes, the reliability of many MTU assessments is not well defined within female populations. Therefore, the purpose of this study was to report the test-retest reliability of local and global MTU function assessments during the early follicular phase of the menstrual cycle. Seventeen naturally menstruating females (age 28.5 {+/-} 7.3 years) completed local and global assessments of MTU function during two testing sessions separated over 24-72 hours. Local tests included Achilles tendon mechanical testing and isometric strength of ankle plantar flexors and knee extensors, whereas global tests included countermovement, squat, and drop jumps, and the isometric midthigh pull. Based on intraclass correlation coefficient (ICC) statistics, poor to excellent reliability was found for local measures (ICC: 0.096-0.936). Good to excellent reliability was found for all global measures (ICC: 0.788-0.985), excluding the eccentric utilisation ratio (ICC 0.738) and most rate of force development metrics (ICC: 0.635-0.912). Isometric midthigh pull peak force displayed excellent reliability (ICC: 0.966), whereas force-time metrics ranged from moderate to excellent (ICC: 0.635-0.970). Excluding rate of force development (coefficient of variation [CV]: 10.6-35.9%), global measures (CV: 1.6-12.9%) were more reproducible than local measures (CV: 3.6-64.5%). However, local metrics directly measure specific aspects of MTU function, and therefore provide valuable information despite lower reproducibility. The novel data reported here provides insight into the natural variability of MTU function within female athletes, which can be used to enhance the interpretation of other female athlete data, especially that which aims to investigate other aspects of variability, such as the menstrual cycle.

physiology↗

bioRxiv2020

T cell responses induced by attenuated flavivirus vaccination are specific and show limited cross-reactivity with other flavivirus species.

Members of the flavivirus genus share a high level of sequence similarity and often circulate in the same geographical regions. However, whether T cells induced by one viral species cross-react with other related flaviviruses has not been globally addressed. Here, we tested pools of epitopes derived from dengue (DENV), zika (ZIKV), Japanese Encephalitis (JEV), West Nile (WNV), and yellow fever (YFV) viruses by Intracellular Cytokine Staining (ICS) using PBMCs of individuals naturally exposed to DENV or immunized with DENV (TV005) or YF17D vaccines. CD8 T cell responses recognized epitopes from multiple flaviviruses, however, the magnitude of cross-reactive responses was consistently several-fold lower than those to the autologous epitope pools, and associated with lower expression of activation markers such as CD40L, CD69, and CD137. Next, we characterized the antigen sensitivity of short-term T cell lines (TCL) representing twenty-nine different individual epitope/donor combinations. TCL derived from DENV monovalent vaccinees induced CD8 and CD4 T cells that cross-reacted within the DENV serocomplex but were consistently associated with more than 100-fold lower antigen sensitivity for most other flaviviruses, with no cross-recognition of YFV derived peptides. CD8 and CD4 TCL from YF17D vaccinees were associated with very limited cross-reactivity with any other flaviviruses, and in five out of eight cases more than 1000-fold lower antigen sensitivity. Overall, our data suggest limited cross-reactivity for both CD4 and CD8 T cell responses between flaviviruses and has implications for understanding immunity elicited by natural infection, and strategies to develop live attenuated vaccines against flaviviral species. ImportanceThe envelope (E) protein is the dominant target of neutralizing antibodies for dengue virus (DENV) and yellow fever virus (YFV). Accordingly, several DENV vaccine constructs use the E protein in a live attenuated vaccine format, utilizing a backbone derived from a heterologous flavivirus (such as YF) as a delivery vector. This backbone comprises the non-structural (NS) and capsid (C) antigens which are dominant targets of T cell responses. Here, we demonstrate that cross-reactivity at the level of T cell responses amongst different flaviviruses is very limited, despite high levels of sequence homology. Thus, the use of heterologous flavivirus species as a live attenuated vaccine vector is not likely to generate optimal T cell responses, and might thus impair vaccine performance.

immunology↗