ABSTRACT
mRNA vaccines have been shown to be safe and effective in individuals with cancer. It is unclear, however, if systemic anti-cancer therapy impacts the coordinated cellular and humoral immune responses elicited by SARS-CoV-2 mRNA vaccines. To fill this knowledge gap, we assessed SARS-CoV-2 mRNA vaccine-elicited immunity in a cohort of patients with advanced solid tumors either under observation or receiving systemic anti-cancer therapy. This analysis revealed that SARS-CoV-2 mRNA vaccine-elicited cellular and humoral immunity was not significantly different in individuals with cancer receiving systemic anti-cancer therapy relative to individuals under observation. Furthermore, even though some patients exhibited suboptimal antibody titers after vaccination, SARS-CoV-2 specific cellular immune responses were still detected. These data suggest that antibody titers offer an incomplete picture of vaccine-elicited SARS-CoV-2 immunity in cancer patients undergoing active systemic anti-cancer therapy, and that vaccine-elicited cellular immunity exists even in the absence of significant quantities of SARS-CoV-2 specific antibodies.
ABSTRACT
BACKGROUND: Alzheimer's disease (AD) is the most common neurodegenerative disorder, manifesting clinical symptoms of cognitive impairment and dementia. The vast majority of cases are late onset AD (LOAD), which are genetically heterogeneous and occur sporadically. The neuropathological changes of LOAD can be reproduced by supplementing a rabbit's diet with 2% cholesterol for 12 weeks. METHODS: In the present study, a non-targeted Fourier transform ion cyclotron resonance mass spectrometry based metabolomics approach and multivariate statistics were used to survey the effect of cholesterol on cerebrospinal fluid metabolites over a 12 week time-course. RESULTS: Of the 6515 accurate masses detected in the rabbit CSF, 375 showed significant differences in intensity (p < 0.05) between samples collected at different time points. Further analysis of top 95 (p < 0.01) revealed four clusters of metabolites with different expression patterns throughout the course of the cholesterol treatment. The majority of effects were observed in 12 weeks of cholesterol treated samples, while certain masses showed transient changes at 8 weeks but returned back to near the levels of the controls at 12 weeks. The masses that started to change 8 weeks into the treatment may represent early metabolic changes linked to certain defects in the brain related to AD development. Putative metabolite identifications revealed certain phosphorylated glycerolipids and peptide fragments decreased after 8 weeks of cholesterol treatment. CONCLUSION: This study showed that there are specific metabolic perturbations which occur in the CSF as a result of high cholesterol loading. Given the changes of short peptide fragments in particular, the effects are likely the consequence of brain degeneration caused by high cholesterol levels. Further investigations of these masses will lead to a greater understanding of the metabolic mechanisms associated with cholesterol-related AD development. Some of these masses may be used as candidates for the development of diagnostic, prognostic or theranostic markers.
