HPV Serology Testing Confirms High HPV Immunisation Coverage in England

Background

Reported human papillomavirus (HPV) vaccination coverage in England is high, particularly in girls offered routine immunisation at age 12 years. Serological surveillance can be used to validate reported coverage and explore variations within it and changes in serological markers over time.

Methods

Residual serum specimens collected from females aged 15–19 years in 2010–2011 were tested for anti-HPV16 and HPV18 IgG by ELISA. Based on these results, females were classified as follows: seronegative, probable natural infection, probable vaccine-induced seropositivity, or possible natural infection/possible vaccine-induced seropositivity. The proportion of females with vaccine-induced seropositivity was compared to the reported vaccination coverage.

Results

Of 2146 specimens tested, 1380 (64%) were seropositive for both types HPV16 and HPV18 and 159 (7.4%) positive for only one HPV type. The IgG concentrations were far higher for those positive for both HPV types than those positive for only one HPV type. 1320 (62%) females were considered to have probable vaccine-induced seropositivity. Among vaccine-induced seropositives, antibody concentrations declined with increasing age at vaccination and increasing time since vaccination.

Conclusions

The proportion of females with vaccine-induced seropositivity was closest to the reported 3-dose coverage in those offered the vaccination at younger ages, with a greater discrepancy in the older females. This suggests either some under-reporting of immunisations of older females and/or that partial vaccination (i.e. one- or two-doses) has provided high antibody responses in 13–17 year olds.     

A fluorescence-based assay for indoleamine 2,3-dioxygenase

A rapid and sensitive fluorescence-based bioassay for determination of indoleamine 2,3-dioxygenase (IDO) activity has been developed. This assay relies on the quantification of the amount of kynurenine produced in the assay medium by fluorescence and complements the standard absorbance and high-performance liquid chromatography (HPLC) assay methods. The fluorescence method has limits of detection similar to those of the standard assay methods. Measured activities of IDO, including in the presence of tryptophan-based inhibitors, were in statistical agreement with the absorbance and HPLC assay methods. The fluorescence-based assay was also suitable for assessment of IDO inhibition by compounds that are incompatible with the absorbance method.     

The association of the sulphogalactosylglycerolipid of rat brain with myelination

The sulphogalactosylglycerolipid of rat brain is closely associated with the process of myelination, as demonstrated by the following observations. 1. The lipid is barely detectable in rat brain before 10 days of age, accumulates rapidly between age 10 and 25 days, and remains relatively constant in amount (between 0.3 and 0.4mumol per brain) thereafter into adult life. 2. The activity of adenosine 3'-phosphate 5'-sulphatophosphate-galactosyldiacylglycerol sulphotransferase is almost absent before 10 days of age, attains a maximum at age 20 days, and slowly decreases thereafter with increasing age. This developmental pattern correlates well with that of other myelin-specific metabolites. 3. Both the concentration of the sulphogalactosylglycerolipid and the activity of sulphotransferase are greatly decreased in the non-myelinating jimpy mouse. 4. The myelin fraction of rat brain contains most of the sulphogalactosylglycerolipid. The lipid occurs in a diacyl and an alkylacyl form. Determinations of the relative amount of each type in brain showed about a 1:1 mixture in both 21-day-old and adult rats. Rats injected with H(2) (35)SO(4) at 20 days of age lost (35)S from the diacyl form at a higher rate than from the alkylacyl compound over a 21-day period. These data suggest that the diacyl form has a higher turnover than the alkylacyl derivative. The percentage of the total sulpholipid content of brain contributed by the sulphogalactosylglycerolipid is 16% in 21-day-old rats and 8.4% in adult rats.     

Response of soil organic matter pools to elevated CO2 and warming in a semi-arid grassland

Warming and elevated atmospheric CO₂ (eCO₂) can elicit contrasting responses on different SOM pools, thus to understand the effects of combined factors it is necessary to evaluate individual pools. Over two years, we assessed responses to eCO₂ and warming of SOM pools, their susceptibility to decomposition, and whether these responses were mediated by plant inputs in a semi-arid grassland at the PHACE (Prairie Heating and CO₂ Enrichment) experiment. We used long-term soil incubations and assessed relationships between plant inputs and the responses of the labile and resistant pools. We found strong and contrasting effects of eCO₂ and warming on the labile C pool. In 2008 labile C was increased by eCO₂ and was positively related to plant biomass. In contrast, in 2007 eCO₂ and warming had interactive effects on the labile C, and the pool size was not related to plant biomass. Effects of warming and eCO₂ in this year were consistent withtreatment effects on soil moisture and temperature and their effects on labile C decomposition. The decomposition rate of the resistant C was positively related to indicators of plant C inputs. Our approach demonstrated that SOM pools in this grassland can have early and contrasting responses to climate change factors. The labile C pool in the mixed-grass prairie was highly responsive to eCO₂ and warming but the factors behind such responses were highly dynamic across years. Results suggest that in this grassland the resistant C pool could be negatively affected by increases in plant-production driven available soil C.     

The discovery of the benzazepine class of histamine H3 receptor antagonists

This Letter describes the discovery of a novel series of H₃ receptor antagonists. The initial medicinal chemistry strategy focused on deconstructing and simplifying an early screening hit which rapidly led to the discovery of a novel series of H₃ receptor antagonists based on the benzazepine core. Employing an H₃ driven pharmacodynamic model, the series was then further optimised through to a lead compound that showed robust in vivo functional activity and possessed overall excellent developability properties.