Uptake of first two doses of human papillomavirus vaccine by adolescent schoolgirls in Manchester: prospective cohort study

Objective To assess the feasibility and acceptability of delivering a human papillomavirus (HPV) vaccine to adolescent girls.Design Prospective cohort study.Setting 36 secondary schools in two primary care trusts in Greater Manchester, United Kingdom.Participants 2817 schoolgirls in year 8 (12 and 13 year olds).Intervention Delivery of the bivalent vaccine at 0, 1, and 6 months over one school year.Main outcome measures Vaccine uptake for doses 1 and 2 of a three dose schedule.Results Vaccine uptake was 70.6% (1989/2817) for the first dose and 68.5% (1930/2817) for the second dose. Uptake was significantly lower in schools with a higher proportion of ethnic minority girls (P<0.001 for trend) or higher proportion of girls entitled to free school meals (P=0.029 for trend). The main reason for parents’ refusal of vaccination was insufficient information about the vaccine and its long term safety. Maintaining the vaccine schedule was challenging as 16.3% (dose 1) and 23.6% (dose 2) of girls missed their vaccination day and had to be offered alternative appointments. No serious adverse events were reported.Conclusion Delivery of the first two doses of HPV vaccine to adolescent schoolgirls is encouraging, but the success of the vaccination programme depends on high coverage for the third dose.     

Testosterone inhibits growth in juvenile male eastern fence lizards (Sceloporus undulatus): implications for energy allocation and sexual size dimorphism

In the eastern fence lizard, Sceloporus undulatus, female-larger sexual size dimorphism develops because yearling females grow faster than males before first reproduction. This sexual growth divergence coincides with maturational increases in male aggression, movement, and ventral coloration, all of which are influenced by the sex steroid testosterone (T). These observations suggest that male growth may be constrained by energetic costs of activity and implicate T as a physiological regulator of this potential trade-off. To test this hypothesis, we used surgical castration and subsequent administration of exogenous T to alter the physiological and behavioral phenotypes of field-active males during the period of sexual growth divergence. As predicted, T inhibited male growth, while castration promoted long-term growth. Males treated with T also exhibited increased daily activity period, movement, and home range area. Food consumption did not differ among male treatments or sexes, suggesting that the inhibitory effects of T on growth are mediated by patterns of energy allocation rather than acquisition. On the basis of estimates derived from published data, we conclude that the energetic cost of increased daily activity period following T manipulation is sufficient to explain most (79%) of the associated reduction in growth. Further, growth may have been constrained by additional energetic costs of increased ectoparasite load following T manipulation. Similar studies of the proximate behavioral, ecological, and physiological mechanisms involved in growth regulation should greatly improve our understanding of sexual size dimorphism.     

A shared epitope of the interphotoreceptor retinoid-binding protein recognized by the CD4+ and CD8+ autoreactive T cells

We previously demonstrated that cultures of rat uveitogenic T cells rapidly become dominated by CD4+ cells, but activation of CD8+ autoreactive T cells also occurred during the in vitro culture of in vivo-primed T cells. In the present study, we show that the commonly used uveitogenic peptide, interphotoreceptor retinoid-binding protein (IRBP) 1-20, generated both CD4+ and CD8+ autoreactive T cells in the C57BL/6 (B6) mouse and that this 20-mer contains at least two distinct antigenic epitopes. To determine whether the CD8 response was Ag-specific and whether CD4+ and CD8+ IRBP1-20-specific T cells recognize distinct antigenic epitopes, we prepared highly purified CD4+ and CD8+ T cells from IRBP1-20-primed mice and tested their proliferative response to a large panel of truncated peptides derived from IRBP1-20. The results showed that both CD4+ and CD8+ T cells recognized the same spectrum of peptides. In addition, peptides P10-18 were found to bind effectively to CD8+ IRBP1-20-specific T cells when complexed with recombinant H-2K(b) and also stimulate the proliferation and cytokine production of CD4+ IRBP1-20-specific T cells. Our results document for the first time that CD8+ and CD4+ autoreactive T cells display characteristic epitope recognition and they both recognize the same core epitope.     

Metabolic flux analysis of HEK-293 cells in perfusion cultures for the production of adenoviral vectors

To meet increasing needs of adenovirus vectors for gene therapy programs, development of efficient and reproducible production processes is required. Perfusion cultures were employed to allow infection at greater cell concentrations. In an effort to define culture conditions resulting in enhanced productivities, experiments performed at different feed rates and infected at various cell densities were compared using metabolic flux analysis. The highest specific product yields were achieved in experiments performed at high perfusion rates and/or low cell concentrations. The intracellular flux analysis revealed that these experiments exhibited greater glycolytic fluxes, slightly higher TCA fluxes, and greater ATP production rates at the time of infection. In contrast, cultures infected at high cell density and/or low medium renewal rates were characterized by a more efficient utilization of glucose at the time of infection, but the specific product yields achieved were lower. The intracellular flux analysis provided a rational basis for the implementation of a feeding strategy that allowed successful infection at a density of 5x10(6)cells/ml.