Abstract
Saliva omics has immense potential for non-invasive diagnostics, including monitoring very young or elderly populations, or individuals in remote locations. In this study, multiple saliva omics from an individual were monitored over three periods (100 timepoints) involving: (1) hourly sampling over 24 h without intervention, (2) hourly sampling over 24 h including immune system activation using the standard 23-valent pneumococcal polysaccharide vaccine, (3) daily sampling for 33 days profiling the post-vaccination response. At each timepoint total saliva transcriptome and proteome, and small RNA from salivary extracellular vesicles were profiled, including mRNA, miRNA, piRNA and bacterial RNA. The two 24-h periods were used in a paired analysis to remove daily variation and reveal vaccination responses. Over 18,000 omics longitudinal series had statistically significant temporal trends compared to a healthy baseline. Various immune response and regulation pathways were activated following vaccination, including interferon and cytokine signaling, and MHC antigen presentation. Immune response timeframes were concordant with innate and adaptive immunity development, and coincided with vaccination and reported fever. Overall, mRNA results appeared more specific and sensitive (timewise) to vaccination compared to other omics. The results suggest saliva omics can be consistently assessed for non-invasive personalized monitoring and immune response diagnostics.
Highlights
Saliva omics has immense potential for non-invasive diagnostics, including monitoring very young or elderly populations, or individuals in remote locations
In the second 24 h time frame (TFH2), the subject was vaccinated with pneumococcal polysaccharide vaccine (PPSV23) within 3.5 h of waking up, while otherwise maintaining a similar routine as in the first period, and again saliva samples were taken hourly
The time series trends observed were indicative of immune response, which coincided in timing with the vaccination, and fever reported by our subject
Summary
Saliva omics has immense potential for non-invasive diagnostics, including monitoring very young or elderly populations, or individuals in remote locations. Additional developments have included utilizing host–microbiome data in insulin resistant individuals in a study of weight g ain[8] and in prediabetics[9], investigating biological a ge[10,11] as well as monitoring of astronauts in the recent NASA twin study[12] In this investigation we are extending integrative omics to evaluate the utility of such monitoring using saliva. We are carrying out a clinical trial monitoring individualized response to pneumococcal vaccination, and in a proof-of-principle case-study, we monitored individualized response to the standard 23-valent pneumococcal polysaccharide vaccination (PPSV23), in a generally healthy individual (Caucasian male, 38, has reported chronic sinusitis), and carried out integrative profiling on saliva pre- and post-vaccination with pneumococcal PPSV23 vaccine This is to our knowledge the most extensive saliva-focused omics dataset on an individual, covering 104 timepoints over one year. The saliva sampled timepoints included three periods of particular reference in this manuscript: (1) 24 h hourly sampling without intervention to assess a healthy hourly baseline, (2) 24 h hourly sampling that included vaccination with pneumococcal vaccine (PPSV23) to assess response to the vaccine, (3) daily sampling following the vaccination to assess potential innate and adaptive immune responses reflected in the molecular saliva components
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