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BackgroundThe emergence of novel SARS-CoV-2 variants that resist neutralizing antibodies drew the attention to cellular immunity and calls for the development of alternative vaccination strategies to combat the pandemic. Here, we have assessed the kinetics of T cell responses and protective efficacy against severe COVID-19 in pre- and post-exposure settings, elicited by PolyPEPI-SCoV-2, a peptide based T cell vaccine.Methods75 Syrian hamsters were immunized subcutaneously with PolyPEPI-SCoV-2 on D0 and D14. On D42, hamsters were intranasally challenged with 102 TCID50 of the virus. To analyze immunogenicity by IFN-γ ELISPOT and antibody secretion, lymphoid tissues were collected both before (D0, D14, D28, D42) and after challenge (D44, D46, D49). To measure vaccine efficacy, lung tissue, throat swabs and nasal turbinate samples were assessed for viral load and histopathological changes. Further, body weight was monitored on D0, D28, D42 and every day after challenge.ResultsThe vaccine induced robust activation of T cells against all SARS-CoV-2 structural proteins that were rapidly boosted after virus challenge compared to control animals (~4-fold, p

Industrial symbiosis is an eco-innovative system concept that is based on a circular economy and industrial ecology ideas. This process comprises the movement of materials, energy, and skills across enterprises located within eco-industrial parks, and strives to provide economic, environmental, and social competitive advantages for all the involved parties. Considering that the agri-food system creates a vast quantity of by-products along the supply chain, it is a sector that has huge potential within material and energy recovery systems and fits well into eco-industrial parks. The current study is a literature review that aims to evaluate the interest exhibited so far by scientific research in the topic of industrial symbiosis in the agri-food sector and to highlight the primary analytical techniques that have been used for this topic. Using the paradigm of multiple correspondence analysis, a content analysis was conducted from which the major themes of the researched phenomena emerged. The results indicate that the topic areas are unrelated and somewhat distant from each other. The analyzed case studies have revealed that the authors had neglected the communicative and collaborative elements among stakeholders, and instead focused on the potential use of some tools and approaches. Furthermore, it has been hypothesized that the hiding of information within a supply chain prevents industrial symbiosis procedures from being implemented. This research suggests the necessity of creating communication and cooperation platforms among stakeholders, which would promote the introduction of new techniques and tools for the development of circular production systems.

Eco-innovations that reduce the environmental effect of manufacturing and consumption are seen as critical components of sustainable development and a critical component of the transition to a circular economy. Food systems address the issue of food waste, which is generally acknowledged as a cost to the economy, the environment, and society. Eco-innovations seem to be critical for the food system's transformation to a more circular model centered on sustainable food production and processing. The goal of this paper was to determine the variables that influenced the introduction of product, process, organizational, and marketing innovations in European Union agri-food enterprises between 2012 and 2014. According to a preliminary analysis of the data, 57.40% of agribusinesses did not implement any form of innovation, which prompted the authors to study the difficulties surrounding innovation development over the 3-year reference period. Several key factors emerge as significant influences on the introduction of product innovations (0.055**); contractual requirements as significant influences on the introduction of process innovations (−0.081***); and environmental incentives as significant influences on the introduction of marketing innovations (0.062***). Additionally, product (0.704***) and process (1.051***) innovations tend to have a greater influence on enterprises' views of circular benefits. The investigation also demonstrates how enterprises and end users interpret the effect of various forms of innovation differently. Indeed, end users, in contrast to how enterprises understand it, believe that organizational (0.611***) and marketing (0.916***) innovations are critical in pursuing circular benefits.

Long-term immunity to coronaviruses likely stems from T cell activity. We present here a novel approach for the selection of immunoprevalent SARS-CoV-2-derived T cell epitopes using an in silico cohort of HLA-genotyped individuals with different ethnicities. Nine 30-mer peptides derived from the four major structural proteins of SARS-CoV-2 were selected and included in a peptide vaccine candidate to recapitulate the broad virus-specific T cell responses observed in natural infection. PolyPEPI-SCoV-2-specific, polyfunctional CD8+ and CD4+ T cells were detected in each of the 17 asymptomatic/mild COVID-19 convalescents' blood against on average seven different vaccine peptides. Furthermore, convalescents' complete HLA-genotype predicted their T cell responses to SARS-CoV-2-derived peptides with 84% accuracy. Computational extrapolation of this relationship to a cohort of 16,000 HLA-genotyped individuals with 16 different ethnicities suggest that PolyPEPI-SCoV-2 vaccination will likely elicit multi-antigenic T cell responses in 98% of individuals, independent of ethnicity. PolyPEPI-SCoV-2 administered with Montanide ISA 51 VG generated robust, Th1-biased CD8+, and CD4+ T cell responses against all represented proteins, as well as binding antibodies upon subcutaneous injection into BALB/c and hCD34+ transgenic mice modeling human immune system. These results have implications for the development of global, highly immunogenic, T cell-focused vaccines against various pathogens and diseases.

Lung cancer is a leading cause of cancer-related death worldwide in both men and women, however mortality in the US and EU are recently declining in parallel with the gradual cut of smoking prevalence. Consequently, the relative frequency of adenocarcinoma increased while that of squamous and small cell carcinomas declined. During the last two decades a plethora of targeted drug therapies have appeared for the treatment of metastasizing non-small cell lung carcinomas (NSCLC). Personalized oncology aims to precisely match patients to treatments with the highest potential of success. Extensive research is done to introduce biomarkers which can predict the effectiveness of a specific targeted therapeutic approach. The EGFR signaling pathway includes several sufficient targets for the treatment of human cancers including NSCLC. Lung adenocarcinoma may harbor both activating and resistance mutations of the EGFR gene, and further, mutations of KRAS and BRAF oncogenes. Less frequent but targetable genetic alterations include ALK, ROS1, RET gene rearrangements, and various alterations of MET proto-oncogene. In addition, the importance of anti-tumor immunity and of tumor microenvironment has become evident recently. Accumulation of mutations generally trigger tumor specific immune defense, but immune protection may be upregulated as an aggressive feature. The blockade of immune checkpoints results in potential reactivation of tumor cell killing and induces significant tumor regression in various tumor types, such as lung carcinoma. Therapeutic responses to anti PD1-PD-L1 treatment may correlate with the expression of PD-L1 by tumor cells. Due to the wide range of diagnostic and predictive features in lung cancer a plenty of tests are required from a single small biopsy or cytology specimen, which is challenged by major issues of sample quantity and quality. Thus, the efficacy of biomarker testing should be warranted by standardized policy and optimal material usage. In this review we aim to discuss major targeted therapy-related biomarkers in NSCLC and testing possibilities comprehensively.