Precise modification of the surface charge of antigen enhances vaccine immunogenicity.

Aluminum (alum) adjuvant is the most extensively used protein subunit vaccine adjuvant, and its effectiveness and safety have been widely recognized. The surface charge of the antigen determines its electrostatic adsorption to alum adjuvant, which directly affects the immune efficacy of the protein vaccine. In our study, we precisely modified its surface charge by inserting charged amino acids into the flexible region of the SARS-CoV-2 receptor-binding domain (RBD), achieving electrostatic adsorption and a site-specific anchor between the immunogen and alum adjuvant. This innovative strategy extended the bioavailability of the RBD and directionally displayed the neutralizing epitopes, thereby significantly enhancing humoral and cellular immunity. Furthermore, the required dose of antigen and alum adjuvant was greatly reduced, which improved the safety and accessibility of the protein subunit vaccine. On this basis, the wide applicability of this novel strategy to a series of representative pathogen antigens such as SARS-RBD, MERS-RBD, Mpox-M1, MenB-fHbp, and Tularemia-Tul4 was further confirmed. Charge modification of antigens provides a straightforward approach for antigenicity optimization of alum-adjuvanted vaccines, which has great potential to be adopted as a global defense against infectious diseases.

Lung-Targeted Transgene Expression of Nanocomplexed Ad5 Enhances Immune Response in the Presence of Preexisting Immunity.

Recombinant adenovirus serotype 5 (Ad5) vector has been widely applied in vaccine development targeting infectious diseases, such as Ebola virus disease and coronavirus disease 2019 (COVID-19). However, the high prevalence of preexisting anti-vector immunity compromises the immunogenicity of Ad5-based vaccines. Thus, there is a substantial unmet need to minimize preexisting immunity while improving the insert-induced immunity of Ad5 vectors. Herein, we address this need by utilizing biocompatible nanoparticles to modulate Ad5-host interactions. We show that positively charged human serum albumin nanoparticles ((+)HSAnp), which are capable of forming a complex with Ad5, significantly increase the transgene expression of Ad5 in both coxsackievirus-adenovirus receptor-positive and -negative cells. Furthermore, in charge- and dose-dependent manners, Ad5/(+)HSAnp complexes achieve robust (up to 227-fold higher) and long-term (up to 60 days) transgene expression in the lungs of mice following intranasal instillation. Importantly, in the presence of preexisting anti-Ad5 immunity, complexed Ad5-based Ebola and COVID-19 vaccines significantly enhance antigen-specific humoral response and mucosal immunity. These findings suggest that viral aggregation and charge modification could be leveraged to engineer enhanced viral vectors for vaccines and gene therapies.

Understanding systemic risk induced by climate change

The systemic risk induced by climate change represents one of the most prominent threats facing humanity and has attracted increasing attention since the outbreak of the COVID-19 pandemic at the end of 2019. The existing literature highlights the importance of systemic risk induced by climate change, but there are still deficiencies in understanding its dynamics and assessing the risk. Aiming to bridge this gap, this study develops a theoretical framework and employs two cases to illustrate the concept, origin, occurrence, propagation, evolution, and assessment framework of systemic risk induced by climate change. The key findings include: 1) systemic risk induced by climate change derives from the rapid growth of greenhouse gas emissions, increasingly complex connections among different socioeconomic systems, and continuous changes in exposure and vulnerability;2) systemic risk induced by climate change is a holistic risk generated by the interconnection, interaction, and dynamic evolution of different types of single risks, and its fundamental, defining feature is cascading effects. The extent of risk propagation and its duration depend on the characteristics of the various discrete risks that are connected to make up the systemic risk;3) impact domains, severity of impact, and probability of occurrences are three core indicators in systemic risk assessment, and the impact domains should include the economy, society, homeland security, human health, and living conditions. We propose to deepen systemic risk research from three aspects: to develop theories to understand the mechanism of systemic risk;to conduct empirical research to assess future risks;and to develop countermeasures to mitigate the risk.