Inside-out assembly of viral antigens for the enhanced vaccination.

Current attempts in vaccine delivery systems concentrate on replicating the natural dissemination of live pathogens, but neglect that pathogens evolve to evade the immune system rather than to provoke it. In the case of enveloped RNA viruses, it is the natural dissemination of nucleocapsid protein (NP, core antigen) and surface antigen that delays NP exposure to immune surveillance. Here, we report a multi-layered aluminum hydroxide-stabilized emulsion (MASE) to dictate the delivery sequence of the antigens. In this manner, the receptor-binding domain (RBD, surface antigen) of the spike protein was trapped inside the nanocavity, while NP was absorbed on the outside of the droplets, enabling the burst release of NP before RBD. Compared with the natural packaging strategy, the inside-out strategy induced potent type I interferon-mediated innate immune responses and triggered an immune-potentiated environment in advance, which subsequently boosted CD40+ DC activations and the engagement of the lymph nodes. In both H1N1 influenza and SARS-CoV-2 vaccines, rMASE significantly increased antigen-specific antibody secretion, memory T cell engagement, and Th1-biased immune response, which diminished viral loads after lethal challenge. By simply reversing the delivery sequence of the surface antigen and core antigen, the inside-out strategy may offer major implications for enhanced vaccinations against the enveloped RNA virus.

Forecasting green bond volatility via novel heterogeneous ensemble approaches

Green bonds are powerful tools for fighting against climate change and typically exhibit more volatility than conventional bonds do. However, the volatility forecasting of green bond has received little attention in previous literature. This study proposes two novel heterogeneous ensemble models, which differ from common volatility forecasting in that they are combine advanced tree-based ensemble models and exogenous predictors from other financial and commodity markets to forecast the volatility of green bonds. Validated on multiple green bonds indexes, loss functions, and time horizons, the comparative results show that the incorporation of exogenous predictors can enhance the predictive accuracy of volatility forecasting models, which is also confirmed by the marginal effects illustrated by SHapley Additive exPlanations (SHAP) values. The proposed EX-SEL model significantly outperforms the benchmark models in most cases. The results of the robustness check further indicate that the empirical results are robust to alternative volatility estimators, extreme events such as the COVID-19 pandemic, and alternative selection strategies.

COVID-19 Vaccines: Particulate Alum via Pickering Emulsion for an Enhanced COVID-19 Vaccine Adjuvant (Adv. Mater. 40/2020)

For enhanced COVID-19 vaccines, in article number 2004210, Yufei Xia, Guanghui Ma, and co-workers pack licensed alum on a squalene/water interphase. Thereby, this century-old adjuvant ?travels through time? in a new form of alum-stabilized Pickering emulsion (PAPE), which not only inherits the clinically acknowledged biosafety, but also demonstrates enhanced cellular uptake and cross-presentation of antigens for potent humoral and cellular responses.

Particulate Alum via Pickering Emulsion for an Enhanced COVID-19 Vaccine Adjuvant.

For rapid response against the prevailing COVID-19 (coronavirus disease 19), it is a global imperative to exploit the immunogenicity of existing formulations for safe and efficient vaccines. As the most accessible adjuvant, aluminum hydroxide (alum) is still the sole employed adjuvant in most countries. However, alum tends to attach on the membrane rather than entering the dendritic cells (DCs), leading to the absence of intracellular transfer and process of the antigens, and thus limits T-cell-mediated immunity. To address this, alum is packed on the squalene/water interphase is packed, forming an alum-stabilized Pickering emulsion (PAPE). "Inheriting" from alum and squalene, PAPE demonstrates a good biosafety profile. Intriguingly, with the dense array of alum on the oil/water interphase, PAPE not only adsorbs large quantities of SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) antigens, but also harbors a higher affinity for DC uptake, which provokes the uptake and cross-presentation of the delivered antigens. Compared with alum-treated groups, more than six times higher antigen-specific antibody titer and three-fold more IFN-γ-secreting T cells are induced, indicating the potent humoral and cellular immune activations. Collectively, the data suggest that PAPE may provide potential insights toward a safe and efficient adjuvant platform for the enhanced COVID-19 vaccinations.