Immunogenicity and safety of human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccine in healthy boys aged 10-18 years.

PURPOSE: The human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccine (Cervarix) has been shown to be well-tolerated and immunogenic in females aged 10 to 55 years, and up to 100% effective for the prevention of HPV-16/18 infection and associated precancerous cervical lesions in females aged 15 to 25 years. This study is the first to evaluate the immunogenicity and safety of the vaccine in males. METHODS: Healthy males aged 10 to 18 years were randomized (2:1 ratio) to receive HPV-16/18 AS04-adjuvanted vaccine (n = 181) or hepatitis B virus (HBV) control vaccine (n = 89) at 0, 1, and 6 months, and were followed for 7 months. RESULTS: All initially seronegative subjects in the HPV-16/18 group seroconverted for HPV-16 and 18 (ELISA) at month 2. At month 7, all subjects were seropositive, and the HPV-16 and -18 antibody levels were, respectively, four- and twofold higher than at month 2. The anti-HPV-16 and -18 antibody responses for males aged 10 to 18 years and 10 to 14 years, respectively, were higher than those reported for females aged 15 to 25 years and 10 to 14 years, respectively, in a previous study. The reactogenicity profiles of the HPV-16/18 AS04 and HBV vaccines were similar, except that pain and swelling at the injection site were more common in the HPV-16/18 group. However, vaccine-related symptoms did not affect compliance with the three-dose course, which was equally high (97%) in both groups. CONCLUSIONS: The HPV-16/18 AS04-adjuvanted vaccine is immunogenic and well tolerated in boys aged 10 to 18 years. However, further data on the potential public health benefits of vaccination of boys are required before any recommendations can be made.

Global transcript profiles of fat in monozygotic twins discordant for BMI: pathways behind acquired obesity.

BACKGROUND: The acquired component of complex traits is difficult to dissect in humans. Obesity represents such a trait, in which the metabolic and molecular consequences emerge from complex interactions of genes and environment. With the substantial morbidity associated with obesity, a deeper understanding of the concurrent metabolic changes is of considerable importance. The goal of this study was to investigate this important acquired component and expose obesity-induced changes in biological pathways in an identical genetic background. METHODS AND FINDINGS: We used a special study design of "clonal controls," rare monozygotic twins discordant for obesity identified through a national registry of 2,453 young, healthy twin pairs. A total of 14 pairs were studied (eight male, six female; white), with a mean +/- standard deviation (SD) age 25.8 +/- 1.4 y and a body mass index (BMI) difference 5.2 +/- 1.8 kg/m(2). Sequence analyses of mitochondrial DNA (mtDNA) in subcutaneous fat and peripheral leukocytes revealed no aberrant heteroplasmy between the co-twins. However, mtDNA copy number was reduced by 47% in the obese co-twin's fat. In addition, novel pathway analyses of the adipose tissue transcription profiles exposed significant down-regulation of mitochondrial branched-chain amino acid (BCAA) catabolism (p < 0.0001). In line with this finding, serum levels of insulin secretion-enhancing BCAAs were increased in obese male co-twins (9% increase, p = 0.025). Lending clinical relevance to the findings, in both sexes the observed aberrations in mitochondrial amino acid metabolism pathways in fat correlated closely with liver fat accumulation, insulin resistance, and hyperinsulinemia, early aberrations of acquired obesity in these healthy young adults. CONCLUSIONS: Our findings emphasize a substantial role of mitochondrial energy- and amino acid metabolism in obesity and development of insulin resistance.