Profiling of serum factors associated with Staphylococcus aureus skin and soft tissue infections as a foundation for biomarker identification.

Background: People living in close quarters, such as military trainees, are at increased risk for skin and soft tissue infections (SSTI), especially those caused by methicillin-resistant Staphylococcus aureus (MRSA). The serum immune factors associated with the onset of SSTI are not well understood. Methods: We conducted a longitudinal study of SSTIs, enrolling US Army trainees before starting military training and following up for 14 weeks. Samples were collected on Day 0, 56, and 90. Serum chemokines and cytokines among 16 SSTI cases and 51 healthy controls were evaluated using an electro-chemiluminescence based multiplex assay platform. Results: Of 54 tested cytokines, 12 were significantly higher among SSTI cases as compared to controls. Among the cases, there were correlations between factors associated with vascular injury (i.e., VCAM-1, ICAM-1, and Flt1), the angiogenetic factor VEGF, and IL-10. Unsupervised machine learning (Principal Component Analysis) revealed that IL10, IL17A, C-reactive protein, ICAM1, VCAM1, SAA, Flt1, and VGEF were indicative of SSTI. Conclusion: The study demonstrates the power of immunoprofiling for identifying factors predictive of pre-illness state of SSTI thereby identifying early stages of an infection and individuals susceptible to SSTI.

Nasal microbiota evolution within the congregate setting imposed by military training.

The human microbiome is comprised of a complex and diverse community of organisms that is subject to dynamic changes over time. As such, cross-sectional studies of the microbiome provide a multitude of information for a specific body site at a particular time, but they fail to account for temporal changes in microbial constituents resulting from various factors. To address this shortcoming, longitudinal research studies of the human microbiome investigate the influence of various factors on the microbiome of individuals within a group or community setting. These studies are vital to address the effects of host and/or environmental factors on microbiome composition as well as the potential contribution of microbiome members during the course of an infection. The relationship between microbial constituents and disease development has been previously explored for skin and soft tissue infections (SSTIs) within congregate military trainees. Accordingly, approximately 25% of the population carries Staphylococcus aureus within their nasal cavity, and these colonized individuals are known to be at increased risk for SSTIs. To examine the evolution of the nasal microbiota of U.S. Army Infantry trainees, individuals were sampled longitudinally from their arrival at Fort Benning, Georgia, until completion of their training 90 days later. These samples were then processed to determine S. aureus colonization status and to profile the nasal microbiota using 16S rRNA gene-based methods. Microbiota stability differed dramatically among the individual trainees; some subjects exhibited great stability, some subjects showed gradual temporal changes and some subjects displayed a dramatic shift in nasal microbiota composition. Further analysis utilizing the available trainee metadata suggests that the major drivers of nasal microbiota stability may be S. aureus colonization status and geographic origin of the trainees. Nasal microbiota evolution within the congregate setting imposed by military training is a complex process that appears to be affected by numerous factors. This finding may indicate that future campaigns to prevent S. aureus colonization and future SSTIs among high-risk military trainees may require a 'personalized' approach.

Safety, immunogenicity, and efficacy of NDV-3A against Staphylococcus aureus colonization: A phase 2 vaccine trial among US Army Infantry trainees.

BACKGROUND: Military trainees are at increased risk for Staphylococcus aureus colonization and infection. Disease prevention strategies are needed, but a S. aureus vaccine does not currently exist. METHODS: We enrolled US Army Infantry trainees (Fort Benning, GA) in a phase 2, randomized, double-blind, placebo-controlled trial of NDV-3A, a vaccine containing a recombinant adhesin/invasion protein of Candida albicans that has structural similarity to the S. aureus protein clumping factor A. Study participants received one intramuscular dose of NDV-3A or placebo (adjuvant alone) within 72 h of arrival on base. Longitudinal nasal and oral (throat) swabs were collected throughout the 14-week Infantry training cycle. Safety, immunogenicity, and efficacy of NDV-3A against S. aureus nasal / oral acquisition were the endpoints. RESULTS: The NDV-3A candidate had minimal reactogenicity and elicited robust antigen-specific B- and T-cell responses. During the 56-day post-vaccination period, there was no difference in the incidence of S. aureus nasal acquisition between those who were randomized to receive NDV-3A vs. placebo (25.6% vs. 29.1%; vaccine efficacy [VE]: 12.1%; p = 0.31). In time-to-event analysis, there was no difference between study groups with respect to the S. aureus colonization-free interval (VE: 13%; p = 0.29). Similarly, the efficacy of NDV-3A against S. aureus oral acquisition was poor (VE: 2.4%; p = 0.52). CONCLUSIONS: A single dose of NDV-3A did not prevent nasal nor oral acquisition of S. aureus in a population of military trainees at high risk for colonization.