Enhancing anti-tumor immunity through local gene delivery to lymph nodes

Biodegradable polymer carriers offer attractive features for therapeutic cancer vaccines including delivery of multiple vaccine components, efficient internalization, and sustained release of adjuvants and tumor-associated antigens (TAAs). We previously demonstrated that local delivery of depots containing nucleic acid-based toll-liked receptor agonists (TLRas) to lymph nodes (LNs) potently enhances antigen-specific T cell immunity. Building on this work, we hypothesized that local LN delivery of microparticles loaded with TAA-encoding plasmid DNA (pDNA) and TLRas might drive strong local expression and presentation of antigen by LN-resident antigen presenting cells. These effects could help drive more potent and effective CD8+ T cell functions that slow or stop tumor growth.https://doi.org/10.1186/2051-1426-3-S2-P43

Scoping carbon dioxide removal options for Germany–What is their potential contribution to Net-Zero CO2_{2}?

In its latest assessment report the IPCC stresses the need for carbon dioxide removal (CDR) to counterbalance residual emissions to achieve net zero carbon dioxide or greenhouse gas emissions. There are currently a wide variety of CDR measures available. Their potential and feasibility, however, depends on context specific conditions, as among others biophysical site characteristics, or availability of infrastructure and resources. In our study, we selected 13 CDR concepts which we present in the form of exemplary CDR units described in dedicated fact sheets. They cover technical CO2 removal (two concepts of direct air carbon capture), hybrid solutions (six bioenergy with carbon capture technologies) and five options for natural sink enhancement. Our estimates for their CO2 removal potentials in 2050 range from 0.06 to 30 million tons of CO2, depending on the option. Ten of the 13 CDR concepts provide technical removal potentials higher than 1 million tons of CO2 per year. To better understand the potential contribution of analyzed CDR options to reaching net-zero CO2 emissions, we compare our results with the current CO2 emissions and potential residual CO2 emissions in 2050 in Germany. To complement the necessary information on technology-based and hybrid options, we also provide an overview on possible solutions for CO2 storage for Germany. Taking biophysical conditions and infrastructure into account, northern Germany seems a preferable area for deployment of many concepts. However, for their successful implementation further socio-economic analysis, clear regulations, and policy incentives are necessary

Melting, bubble-like expansion and explosion of superheated plasmonic nanoparticles

We report on time-resolved coherent diffraction imaging of gas-phase silver nanoparticles, strongly heated via their plasmon resonance. The x-ray diffraction images reveal a broad range of phenomena for different excitation strengths, from simple melting over strong cavitation to explosive disintegration. Molecular dynamics simulations fully reproduce this behavior and show that the heating induces rather similar trajectories through the phase diagram in all cases, with the very different outcomes being due only to whether and where the stability limit of the metastable superheated liquid is crossed.Comment: 17 pages, 8 figures (including supplemental material

Evolution of long-term vaccine-induced and hybrid immunity in healthcare workers after different COVID-19 vaccine regimens

BACKGROUND: Both infection and vaccination, alone or in combination, generate antibody and T cell responses against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, the maintenance of such responses-and hence protection from disease-requires careful characterization. In a large prospective study of UK healthcare workers (HCWs) (Protective Immunity from T Cells in Healthcare Workers [PITCH], within the larger SARS-CoV-2 Immunity and Reinfection Evaluation [SIREN] study), we previously observed that prior infection strongly affected subsequent cellular and humoral immunity induced after long and short dosing intervals of BNT162b2 (Pfizer/BioNTech) vaccination. METHODS: Here, we report longer follow-up of 684 HCWs in this cohort over 6-9 months following two doses of BNT162b2 or AZD1222 (Oxford/AstraZeneca) vaccination and up to 6 months following a subsequent mRNA booster vaccination. FINDINGS: We make three observations: first, the dynamics of humoral and cellular responses differ; binding and neutralizing antibodies declined, whereas T and memory B cell responses were maintained after the second vaccine dose. Second, vaccine boosting restored immunoglobulin (Ig) G levels; broadened neutralizing activity against variants of concern, including Omicron BA.1, BA.2, and BA.5; and boosted T cell responses above the 6-month level after dose 2. Third, prior infection maintained its impact driving larger and broader T cell responses compared with never-infected people, a feature maintained until 6 months after the third dose. CONCLUSIONS: Broadly cross-reactive T cell responses are well maintained over time-especially in those with combined vaccine and infection-induced immunity ("hybrid" immunity)-and may contribute to continued protection against severe disease

A haemagglutination test for rapid detection of antibodies to SARS-CoV-2

Serological detection of antibodies to SARS-CoV-2 is essential for establishing rates of seroconversion in populations, and for seeking evidence for a level of antibody that may be protective against COVID-19 disease. Several high-performance commercial tests have been described, but these require centralised laboratory facilities that are comparatively expensive, and therefore not available universally. Red cell agglutination tests do not require special equipment, are read by eye, have short development times, low cost and can be applied at the Point of Care. Here we describe a quantitative Haemagglutination test (HAT) for the detection of antibodies to the receptor binding domain of the SARS-CoV-2 spike protein. The HAT has a sensitivity of 90% and specificity of 99% for detection of antibodies after a PCR diagnosed infection. We will supply aliquots of the test reagent sufficient for ten thousand test wells free of charge to qualified research groups anywhere in the world

Net‐Zero CO 2 Germany - A Retrospect From the Year 2050

Germany 2050: For the first time Germany reached a balance between its sources of anthropogenic CO2 to the atmosphere and newly created anthropogenic sinks. This backcasting study presents a fictional future in which this goal was achieved by avoiding (∼645 Mt CO2), reducing (∼50 Mt CO2) and removing (∼60 Mt CO2) carbon emissions. This meant substantial transformation of the energy system, increasing energy efficiency, sector coupling, and electrification, energy storage solutions including synthetic energy carriers, sector-specific solutions for industry, transport, and agriculture, as well as natural-sink enhancement and technological carbon dioxide options. All of the above was necessary to achieve a net-zero CO2 system for Germany by 2050

Broad and strong memory CD4(+)and CD8(+)T cells induced by SARS-CoV-2 in UK convalescent individuals following COVID-19

The development of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines and therapeutics will depend on understanding viral immunity. We studied T cell memory in 42 patients following recovery from COVID-19 (28 with mild disease and 14 with severe disease) and 16 unexposed donors, using interferon-γ-based assays with peptides spanning SARS-CoV-2 except ORF1. The breadth and magnitude of T cell responses were significantly higher in severe as compared with mild cases. Total and spike-specific T cell responses correlated with spike-specific antibody responses. We identified 41 peptides containing CD4+ and/or CD8+ epitopes, including six immunodominant regions. Six optimized CD8+ epitopes were defined, with peptide–MHC pentamer-positive cells displaying the central and effector memory phenotype. In mild cases, higher proportions of SARS-CoV-2-specific CD8+ T cells were observed. The identification of T cell responses associated with milder disease will support an understanding of protective immunity and highlights the potential of including non-spike proteins within future COVID-19 vaccine design

T cell assays differentiate clinical and subclinical SARS-CoV-2 infections from cross-reactive antiviral responses

Identification of protective T cell responses against SARS-CoV-2 requires distinguishing people infected with SARS-CoV-2 from those with cross-reactive immunity to other coronaviruses. Here we show a range of T cell assays that differentially capture immune function to characterise SARS-CoV-2 responses. Strong ex vivo ELISpot and proliferation responses to multiple antigens (including M, NP and ORF3) are found in 168 PCR-confirmed SARS-CoV-2 infected volunteers, but are rare in 119 uninfected volunteers. Highly exposed seronegative healthcare workers with recent COVID-19-compatible illness show T cell response patterns characteristic of infection. By contrast, >90% of convalescent or unexposed people show proliferation and cellular lactate responses to spike subunits S1/S2, indicating pre-existing cross-reactive T cell populations. The detection of T cell responses to SARS-CoV-2 is therefore critically dependent on assay and antigen selection. Memory responses to specific non-spike proteins provide a method to distinguish recent infection from pre-existing immunity in exposed populations

Two doses of SARS-CoV-2 vaccination induce robust immune responses to emerging SARS-CoV-2 variants of concern

The extent to which immune responses to natural infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and immunization with vaccines protect against variants of concern (VOC) is of increasing importance. Accordingly, here we analyse antibodies and T cells of a recently vaccinated, UK cohort, alongside those recovering from natural infection in early 2020. We show that neutralization of the VOC compared to a reference isolate of the original circulating lineage, B, is reduced: more profoundly against B.1.351 than for B.1.1.7, and in responses to infection or a single dose of vaccine than to a second dose of vaccine. Importantly, high magnitude T cell responses are generated after two vaccine doses, with the majority of the T cell response directed against epitopes that are conserved between the prototype isolate B and the VOC. Vaccination is required to generate high potency immune responses to protect against these and other emergent variants