DNA vaccination for prostate cancer: key concepts and considerations

While locally confined prostate cancer is associated with a low five year mortality rate, advanced or metastatic disease remains a major challenge for healthcare professionals to treat and is usually terminal. As such, there is a need for the development of new, efficacious therapies for prostate cancer. Immunotherapy represents a promising approach where the host's immune system is harnessed to mount an anti-tumour effect, and the licensing of the first prostate cancer specific immunotherapy in 2010 has opened the door for other immunotherapies to gain regulatory approval. Among these strategies DNA vaccines are an attractive option in terms of their ability to elicit a highly specific, potent and wide-sweeping immune response. Several DNA vaccines have been tested for prostate cancer and while they have demonstrated a good safety profile they have faced problems with low efficacy and immunogenicity compared to other immunotherapeutic approaches. This review focuses on the positive aspects of DNA vaccines for prostate cancer that have been assessed in preclinical and clinical trials thus far and examines the key considerations that must be employed to improve the efficacy and immunogenicity of these vaccines.

Lysosome-associated membrane glycoprotein (LAMP)--preliminary study on a hidden antigen target for vaccination against schistosomiasis

Our previously reported gene atlasing of schistosome tissues revealed transcripts that were highly enriched in the digestive tract of Schistosoma mansoni. From these, we selected two candidates, Sm-LAMP and Sm-NPC2 for testing as vaccine targets. The two molecules were selected on the basis of relatively high expression in the gastrodermis, their potentially important biological function, divergence from homologous molecules of the host and possible apical membrane expression in the gastrodermis. Bacterially expressed recombinant peptides corresponding to regions excluding trans-membrane domains of the selected vaccine targets were used in blinded vaccine trials in CBA mice using alum-CpG as adjuvant. Vaccine trials using the recombinant insoluble Sm-LAMP protein showed 16-25% significant reduction in total worm burden. Faecal egg count reduction was 52% and 60% in two trials, respectively, with similar results for the solubly expressed protein. Liver egg burden was reduced significantly (20% and 38%) with an insoluble recombinant Sm-LAMP in two trials, but not with the soluble recombinant form. Parasite fecundity was not affected by either Sm-LAMP protein preparations in the trials. It is concluded that Sm-LAMP may provide limited protection towards S. mansoni infections but could be used in combination with other vaccine candidates, to provide more comprehensive protection.

IL-1α and inflammasome-independent IL-1β promote neutrophil infiltration following alum vaccination

Despite its long record of successful use in human vaccines, the mechanisms underlying the immunomodulatory effects of alum are not fully understood. Alum is a potent inducer of interleukin-1 (IL-1) secretion in vitro in dendritic cells and macrophages via Nucleotide-binding domain and leucine-rich repeat-containing (NLR) family, pyrin domain-containing 3 (NLRP3) inflammasome activation. However, the contribution of IL-1 to alum-induced innate and adaptive immune responses is controversial and the role of IL-1α following alum injection has not been addressed. This study shows that IL-1 is dispensable for alum-induced antibody and CD8 T cell responses to ovalbumin. However, IL-1 is essential for neutrophil infiltration into the injection site, while recruitment of inflammatory monocytes and eosinophils is IL-1 independent. Both IL-1α and IL-1β are released at the site of injection and contribute to the neutrophil response. Surprisingly, these effects are NLRP3-inflammasome independent as is the infiltration of other cell populations. However, while NLRP3 and caspase 1 were dispensable, alum-induced IL-1β at the injection site was dependent on the cysteine protease cathepsin S. Overall, these data demonstrate a previously unreported role for cathepsin S in IL-1β secretion, show that inflammasome formation is dispensable for alum-induced innate immunity and reveal that IL-1α and IL-1β are both necessary for alum-induced neutrophil influx in vivo.

Evaluation of passive ventilation provision in domestic housing retrofit

Increasing energy efficiency in the residential sector, while maintaining adequate home ventilation for health and well-being, is proving to be a challenge. This study assesses the efficacy of passive ventilation strategies designed to comply with building regulations and imposed after housing energy-efficiency retrofits. In particular, it focuses on the provision of ventilation using background through-wall vents, which remains a common strategy in a number of European countries including Ireland and the UK, where vent sizes, related to floor area, are stipulated in building regulations. A collective of social housing, with background through-wall vents installed post thermal retrofit, is taken as a case study. These homes are modelled to interrogate the impact of the passive ventilation strategy on house air exchange rate and thermal heating energy loads. The reaction of occupants to through-wall vent installation is decidedly negative and many block vents to limit thermal discomfort and heat loss. Simulation studies show significant external air ingress through vents. A wide range of effective air change rates are observed when vents are sized without reference to building airtightness, and significant energy penalties result for the leakier homes. This study evaluates the provision of passive through-wall ventilation as part of a retrofit programme and shows it to have a number of drawbacks that may impact on the health of the building and its occupants and ultimately be at odds with the aims of achieving energy efficiency in the residential sector.

Demonstration of passive plasma lensing of a laser wakefield accelerated electron bunch

We report on the first demonstration of passive all-optical plasma lensing using a two-stage setup. An intense femtosecond laser accelerates electrons in a laser wakefield accelerator (LWFA) to 100 MeVover millimeter length scales. By adding a second gas target behind the initial LWFAstage we introduce a robust and independently tunable plasma lens. We observe a density dependent reduction of the LWFA electron beam divergence from an initial value of 2.3 mrad, down to 1.4 mrad (rms), when the plasma lens is in operation. Such a plasma lens provides a simple and compact approach for divergence reduction well matched to the mm-scale length of the LWFA accelerator. The focusing forces are provided solely by the plasma and driven by the bunch itself only, making this a highly useful and conceptually new approach to electron beam focusing. Possible applications of this lens are not limited to laser plasma accelerators. Since no active driver is needed the passive plasma lens is also suited for high repetition rate focusing of electron bunches. Its understanding is also required for modeling the evolution of the driving particle bunch in particle driven wake field acceleration.

Knowledge and acceptance of Human Papillomavirus (HPV) and HPV vaccination in adolescent boys worldwide: a systematic review

Aim

To determine HPV and HPV vaccine awareness, knowledge and acceptance in male adolescents worldwide.

Methods

A mixed methods systematic review was conducted. In accordance with PRISMA guidelines, relevant literature was identified through an electronic database search using specified keywords from inception to September 2015. Non-interventional studies presented in English that assessed HPV knowledge and provided data on male adolescents were included. If available, data on HPV and HPV vaccine perceptions, attitudes and/or HPV vaccine acceptance were also extracted. All studies were critically appraised to provide an indication of methodological quality. Results were compiled using a convergent synthesis.

Results

22 papers were included. The majority of studies were cross-sectional and conducted in the US and Europe. Across continents, regardless of a country’s HPV vaccination programme status, boys’ knowledge of HPV and/or HPV vaccination was generally low to moderate and significantly lower than female knowledge or awareness. There was a disagreement in the association of knowledge and vaccine acceptance, with higher knowledge not always being predictive of acceptance.

Conclusions

Comparison and synthesis of research concerning HPV knowledge and attitudes was made difficult due to the lack of universal definition of vaccine acceptance, and no universally accepted tool for its measurement or for the measurement of HPV knowledge. It is imperative that future research utilises consistent measures of HPV knowledge and attitudes to facilitate interpretation and comparison across studies internationally. Prospective longitudinal studies would be more informative providing data on factors that influenced the move from vaccine intention to uptake.