The Human Microbiome Project strategy for comprehensive sampling of the human microbiome and why it matters.

The Human Microbiome Project used rigorous good clinical practice standards to complete comprehensive body site sampling in healthy 18- to 40-yr-old adults, creating an unparalleled reference set of microbiome specimens. To ensure that specimens represented minimally perturbed microbiomes, we first screened potential participants using exclusion criteria based on health history, including the presence of systemic diseases (e.g., hypertension, cancer, or immunodeficiency or autoimmune disorders), use of potential immunomodulators, and recent use of antibiotics or probiotics. Subsequent physical examinations excluded individuals based on body mass index (BMI), cutaneous lesions, and oral health. We screened 554 individuals to enroll 300 (149 men and 151 women, mean age 26 yr, mean BMI 24 kg/m, 20.0% racial minority, and 10.7% Hispanic). We obtained specimens from the oral cavity, nares, skin, gastrointestinal tract, and vagina (15 specimens from men and 18 from women). The study evaluated longitudinal changes in an individual's microbiome by sampling 279 participants twice (mean 212 d after the first sampling; range 30-359 d) and 100 individuals 3 times (mean 72 d after the second sampling; range 30-224 d). This sampling strategy yielded 11,174 primary specimens, from which 12,479 DNA samples were submitted to 4 centers for metagenomic sequencing. Our clinical design and well-defined reference cohort has laid a foundation for microbiome research.

Seroprevalence of cytomegalovirus (CMV) and risk factors for infection in adolescent males.

BACKGROUND: Congenital cytomegalovirus (CMV) is a leading cause of disability, including sensorineural hearing loss, developmental delay, and mental retardation. Although the seroprevalence of CMV and associated exposure and behavioral risk factors have been reported in adolescent females, few data exist about males. METHODS: Serum samples were obtained from males aged 12-17 years from June 2006 through July 2007 in Cincinnati, Ohio; Galveston, Texas; and Nashville, Tennessee. The samples were tested for CMV immunoglobulin G antibody with a commercial assay. Participants completed a computer-assisted screening interview to assess 7 risk categories. RESULTS: A total of 397 adolescent males were screened, and 165 (47%) were seropositive. African American race, older age, and exposure to children ≤ 3 years of age in the home were significant predictors of CMV infection in the univariate analysis. Hispanic ethnicity, group living situations, saliva-sharing behaviors, and intimate sexual contact were not associated with CMV infection. However, among those with a history of sexual contact, the number of life-time partners was associated with CMV. In the final multivariate model, CMV seroprevalence was significantly higher in African American subjects (odds ratio [OR], 1.93; 95% confidence interval [CI], 1.27-2.95) and subjects ≥ 14 years of age (OR, 1.1; 95% CI, 1.0-1.28). With each additional risk factor, males had a 1.6 times increased risk of CMV. CONCLUSIONS: CMV infections are common in adolescent males and are associated with African American race and increasing age. Further study is needed to understand these risk factors in preparation for a CMV vaccine targeted at both adolescent males and females.

Seroprevalence and Risk Factors for Cytomegalovirus Infections in Adolescent Females.

BACKGROUND: Congenital cytomegalovirus (CMV) is a leading cause of disability, including sensorineural hearing loss, developmental delay, and mental retardation. Understanding risk factors for acquisition of CMV infection in adolescent females will help determine vaccine strategies. METHODS: Females (12-17 years) were recruited from primary care settings in Cincinnati, Galveston, Houston, and Nashville from June 2006 to July 2010 for a seroepidemiologic study, from which seronegative participants were recruited for a CMV vaccine trial. Participants (n = 1585) responded to questions regarding potential exposures. For those with young children in the home (n = 859), additional questions were asked about feeding and changing diapers, and for those > 14 years of age (n = 1162), questions regarding sexual activity were asked. Serum was evaluated for CMV antibody using a commercial immunoglobulin G assay. RESULTS: Cytomegalovirus antibody was detected in 49% of participants. In the univariate analyses, CMV seroprevalence was significantly higher among African Americans, those with children < 3 years of age in the home, and those with a history of oral, anal, or vaginal intercourse. Among those with young children in the home, feeding children and changing diapers further increased the association with CMV infection. However, in the final multivariate analysis, only African Americans and household contact with young children were associated with CMV infection. CONCLUSIONS: By age 12, evidence of CMV infection was common. Multiple factors regarding race and personal behaviors likely contribute to seroconversion earlier in life.

Safety and immunogenicity of a candidate parvovirus B19 vaccine.

Parvovirus B19 is an important human pathogen causing erythema infectiosum, transient aplastic crisis in individuals with underlying hemolytic disorders and hydropsfetalis. We therefore evaluated a parvovirus B19 virus like particle (VLP) vaccine. The safety and immunogenicity of a 25 µg dose of parvovirus B19 recombinant capsid; 2.5 and 25 µg doses of the recombinant capsid given with MF59; and saline placebo were assessed in healthy adults. Because of 3 unexplained cutaneous events the study was halted after enrollment of 43 subjects and before any subject received their third scheduled dose. The rashes developed 5-9 days after the first or second injection and were seen in one placebo recipient (without an injection site lesion) and two vaccine recipients (with injection site reactions). No clear cause was established. Other safety evaluations revealed mostly injection site reactions that were mild to moderate with an increase in pain in subjects receiving vaccine and MF59. After dose 2 the majority of vaccine recipients developed ELISA and neutralizing antibody to parvovirus B19. Given the possible severe consequences of parvovirus B19 infection, further development of a safe and effective vaccine continues to be important.