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The Covenant of Mayors (CoM) is a successful European initiative which encourages local authorities to be proactive in fighting climate change. Recently, it expanded to cover adaptation and energy access/poverty and became a global initiative. In this study we investigate an additional perspective: synergies and trade-offs between climate and air quality. Signatories pledge to reduce their Greenhouse gas (GHG) emissions and voluntarily report their emissions, energy consumption and the measures that they carry out to reach their goals. We develop a methodology to estimate air pollutant emissions corresponding to CO 2 emissions CoM signatories report, using information they already submit and national estimates of air pollutant emission factors. The methodology is applied to over 1600 signatories in Europe, representing over 80 million inhabitants. Results show that, in general, signatories are reducing both types of emissions. However, there are also cases where emissions increase. We explore the reasons behind these changes and highlight the role of technological improvement. This work calls for an increased coherence between climate and air quality plans at the local scale and provides a first step and a tool to support signatories, even the smallest ones, to move in this direction., (Copyright © 2020 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Transport emissions need to be drastically decreased in order to put Europe on a path towards a long-term climate neutrality. Commercial transport, and especially last mile delivery is expected to grow because of the rise of e-commerce. In this frame, electric light commercial vehicles (eLCVs) can be a promising low-emission solution. Literature holistically analysing the potential of eLCVs as well as related support policies is sparse. This paper attempts to close this research gap. To this aim, the total cost of ownership (TCO) comparisons for eLCVs and benchmark vehicles are performed and support measures that target the improvement of the eLCV TCO are analysed. Various eLCV deployment scenarios until 2030 are explored and their impact on carbon dioxide (CO 2 ) and other pollutant emissions as well as pollutant concentrations are calculated. It is found that while in several European Union (EU) countries eLCVs are already cost competitive, because of fiscal support, some remaining market barriers need to be overcome to pave the way to mass market deployment of eLCVs. High penetration of eLCVs alone can lead to a reduction of total transport CO 2 emissions by more than 3% by 2030. For pollutant emissions, such as nitrogen oxide (NO x ) and particulate matter (PM), the reduction would be equal or even higher. In the case of PM, this can translate to reductions in concentrations by nearly 2% in several urban areas by 2030. Carefully designed support policies could help to ensure that the potential of eLCVs as a low-emission alternative is fully leveraged in the EU., (© 2020 The Authors.)

The SHERPA tool was used to assess the major pollution sources and the geographical areas impacting on the PM 2.5 of the main cities in the Danube and Western Balkans regions. The activity sectors influencing most the PM 2.5 levels in the study area are energy production (22%), agriculture (19%), residential combustion (16%) and road transport (7%). The energy production in inefficient coal-fuelled power plants was identified as one of main source of PM 2.5 in the Western Balkans. As for the geographical origin of PM 2.5 , the transboundary pollution is confirmed as the main origin of PM 2.5 (44%) in the investigated cities, while the city own emissions and the national sources outside the concerned city impact on average 22% and 15%, respectively. An association was observed between the long-range transport and the impact of agriculture and energy production, while both local urban emissions and long-range transport were associated with the residential sector. A special attention is given in this study to biomass, a renewable source, which use is often promoted in the frame of climate and energy policies. Nevertheless, the combustion of biomass in inefficient small appliances has considerable particulate matter emissions and therefore this type of practice impacts negatively on air quality. Considering that biomass is traditionally used in South-East Europe as fuel for residential heating, the interpretation of the model results was supported with the estimation of biomass burning contributions to PM 2.5 obtained with receptor models and data on biomass fuel consumption from the literature. The analysis of the contributions from biomass burning derived from receptor models suggests that biomass burning is the dominant source within the residential heating sector in the studied area and that the emissions from this source are likely underestimated. This study concludes that more effort is needed to improve the estimations of biomass burning emissions and that policies to improve air quality in the cities should involve a geographic context wider than the city level., (Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.)

This study is a first attempt to evaluate how the major efforts made by several European cities in the frame of the Covenant of Mayors (CoM) initiative can impact the air pollution levels in the participating cities. CoM is by no mean one of the major cities initiatives aimed at mitigating climate change, supporting local authorities in the implementation of their climate action plans. Energy savings measures reported in the CoM cities' action plans have been analysed from the air quality perspective in order to find quantitative relations in the way local authorities deal with mitigation and how these practices are expected to have consequences on the air quality at urban level and finally positively impacting the citizens' health. In the paper, the air quality 2713 energy saving measures proposed by 146 cities located in 23 countries in the frame of the CoM are selected and their co-benefits for air quality and public health estimated by means of SHERPA, a fast modelling tool that mimics the behaviour of a full physically-based Chemical Transport Model. Besides evaluating the overall benefits of this subset of mitigation measures for the air quality, the study also investigates the relevance of some factors such as the implementation sector, the city size and the pollution levels in achieving the highest possible co-benefits. The results presented refer to the special field covered by the study, i.e. energy saving measures and are not automatically referable to other types of measures. Nevertheless, they clearly show how climate mitigation and air quality policies are deeply interconnected at the urban level., (Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Poor air quality and related health impacts are still an issue in many cities and regions worldwide. Integrated assessment models (IAMs) can support the design of measures to reduce the emissions of precursors affecting air pollution. In this study, we apply the SHERPA (screening for high emission reduction potentials for air quality) model to compare spatial and sectoral emission reductions, given country-scale emission targets. Different approaches are tested: (a) country "uniform" emission reductions, (b) emission reductions targeting urban areas, (c) emission reductions targeting preferential sectors. As a case study, we apply the approaches to the implementation of the National Emission Ceiling Directive. Results are evaluated in terms of the reduction in average population exposure to PM 2.5 overall in a country and in its main cities. Results indicate that the reduction of population exposure to PM 2.5 highly depends on the way emission reductions are implemented. This work also shows the usefulness of the SHERPA model to support national authorities implementing national emission reduction targets while, at the same time, addressing their local air quality issues.

We have demonstrated recently in a phase Ia clinical trial that synthetic malaria peptides delivered by immuno-potentiating reconstituted influenza virosomes (IRIV) induced long-lived peptide-specific antibody responses in all volunteers. In the current ancillary study to this clinical trial we have investigated the cellular immune responses specific for IRIV and the surface bound synthetic malaria peptides tested. After vaccination, in 50% (8/16) of the volunteers at least one positive lymphoproliferative response specific for the 49mer peptide derived from the Plasmodium falciparum apical membrane antigen-1 (AMA-1) was observed with stimulation indices ranging from 2 to 4.5. All volunteers showed pre-existing IRIV specific cellular immunity assessed by ex vivo IFN-gamma ELISpot analysis and lymphoproliferation. The pre-existing influenza specific T cell responses did not interfere negatively with the induction of malaria peptide-specific humoral and cellular immune responses. Our results support the view that IRIV constitute a safe antigen delivery system for induction of peptide-specific immune responses in human populations.

The circumsporozoite protein (CSP) of Plasmodium falciparum is a leading candidate antigen for inclusion in a malaria subunit vaccine. We describe here the design of a conformationally constrained synthetic peptide, designated UK-39, which has structural and antigenic similarity to the NPNA-repeat region of native CSP. NMR studies on the antigen support the presence of helical turn-like structures within consecutive NPNA motifs in aqueous solution. Intramuscular delivery of UK-39 to mice and rabbits on the surface of reconstituted influenza virosomes elicited high titers of sporozoite crossreactive antibodies. Influenza virus proteins were crucially important for the immunostimulatory activity of the virosome-based antigen delivery system, as a liposomal formulation of UK-39 was not immunogenic. IgG antibodies elicited by UK-39 inhibited invasion of hepatocytes by P. falciparum sporozoites, but not by antigenically distinct P. yoelii sporozoites. Our approach to optimized virosome-formulated synthetic peptide vaccines should be generally applicable for other infectious and noninfectious diseases.

Buruli ulcer (BU) caused by Mycobacterium ulcerans is a chronic necrotizing disease of the skin and the underlying soft tissue. Fat tissue necrosis accompanied by minimal inflammation is considered the most reliable histopathologic feature of BU. There may be a constant influx of inflammatory cells to the sites of active infection but these are thought to be killed by mycolactone, a polyketide toxin produced by M. ulcerans, through apoptosis and necrosis. Here we describe the spatial correlations between mycobacterial load and the expression of dendritic cell (DC) surface markers (cluster of differentiation (CD)83, CD11c, and CD123), the Toll-like receptor (TLR) 9 and pro- and anti-inflammatory cytokines (IL-8, IL-6, tumor necrosis factor-alpha (TNF-alpha), IFN-alpha, IL-12p40, IL-10, and IFN-gamma) within BU lesions. Although IL-8, IL-6, and TNF-alpha messenger RNA (mRNA) was detectable by real-time PCR in all lesions, the expression of the other cytokines was only found as small foci in some lesions. Correlations of the distribution of mRNA encoding the activation marker CD83 and the DC subset markers CD123 and CD11c indicate that both activated plasmacytoid and myeloid dendritic cells were present in the lesions. Results suggest that M. ulcerans specific immune responses may develop once therapeutic interventions have limited the production of mycolactone.

Buruli ulcer (BU), caused by Mycobacterium ulcerans, is the third most common mycobacterial infection in immunocompetent humans besides tuberculosis and leprosy. We have compared by ex vivo enzyme-linked immunospot analysis interferon-gamma (IFN-gamma) responses in peripheral blood mononuclear cells (PBMC) from BU patients, household contacts, and individuals living in an adjacent M. ulcerans nonendemic region. PBMC were stimulated with purified protein derivative (PPD) and nonmycobacterial antigens such as reconstituted influenza virus particles and isopentenyl-pyrophosphate. With all three antigens, the number of IFN-gamma spot-forming units was reduced significantly in BU patients compared with the controls from a nonendemic area. This demonstrates for the first time that M. ulcerans infection-associated systemic reduction in IFN-gamma responses is not confined to stimulation with live or dead mycobacteria and their products but extends to other antigens. Interleukin (IL)-12 secretion by PPD-stimulated PBMC was not reduced in BU patients, indicating that reduction in IFN-gamma responses was not caused by diminished IL-12 production. Several months after surgical excision of BU lesions, IFN-gamma responses of BU patients against all antigens used for stimulation recovered significantly, indicating that the measured systemic immunosuppression was not the consequence of a genetic defect in T cell function predisposing for BU but is rather related to the presence of M. ulcerans bacteria.

In the absence of suitable rodent animal models for Plasmodium falciparum malaria, the efficacy testing of asexual blood-stage vaccine candidates in Aotus nancymaae represents a tool to select between different formulations before conducting expensive human clinical trials. CpG oligonucleotides (ODN) specifically promote the production of pro-inflammatory and Th1-type cytokines and they enhance the immunogenicity of co-administered antigens. Toll like receptor 9 (TLR-9) binds directly and sequence-specifically to single-stranded un-methylated CpG-DNA mediating the biological effects of CpG ODN. We cloned and functionally characterised the TLR-9 cDNA of A. nancymaae. The cDNA encompassed 3,099 bp predicted to code for 1,032 amino acid residues. Results of homology searches to human TLR-9 suggested that the receptor is 93 and 94% identical at the nucleotide and amino acid sequence levels, respectively. Stimulation of splenocytes of A. nancymaae with CpG ODN resulted in proliferative responses in all animals analysed. FACS analysis of cultures incubated with CpG ODN 2006 indicated that the B cell marker CD20 was up-regulated consistent with B cell activation. The high level of sequence conservation of Aona-TLR-9 reinforces the suitability of A. nancymaae as animal model for malaria subunit vaccine development.