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SARS-CoV-2 infection primes cross-protective respiratory IgA in a MyD88- and MAVS-dependent manner
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is constantly evolving mutations in the Spike protein to evade humoral immunity. Respiratory tract antiviral IgA antibodies are superior to circulating IgG antibodies in preventing SARS-CoV-2 infection. However, the role of innate immune signals required for the induction of mucosal IgA against SARS-CoV-2 infection is unknown. Here we show that hamsters recovered from ancestral SARS-CoV-2 infection are cross-protected against heterologous SARS-CoV-2 alpha, gamma, delta, and omicron BA.1 variants. Intranasal vaccination with an inactivated whole virus vaccine completely protects hamsters against heterologous SARS-CoV-2 infection. In addition, we show that intranasal boost vaccination of mice recovered from SARS-CoV-2 infection with unadjuvanted Spike protein induces robust levels of respiratory anti-Spike IgA and protects the mice from a heterologous SARS-CoV-2 infection. Furthermore, our findings suggest that MyD88 and MAVS play a role in the induction of the memory IgA response following an intranasal booster with unadjuvanted Spike protein in mice recovered from the SARS-CoV-2 infection. These findings provide a useful basis for the development of cross-protective mucosal vaccines against heterologous SARS-CoV-2 infection.
Calboxyvinyl polymer adjuvant enhances respiratory iga responses through mucosal and systemic administration
Adjuvants play a crucial role in enhancing vaccine efficacy. Although several adjuvants have been approved, there remains a demand for safer and more effective adjuvants for nasal vaccines. Here, we identified calboxyvinyl polymer (CVP) as a superior mucosal vaccine adjuvant from pharmaceutical base materials using our screening systems; single nasal vaccination of the CVP-combined influenza split vaccine-induced antigen-specific IgA and IgG antibodies and provided protection against lethal influenza virus infection. Furthermore, nasal vaccination with CVP-combined severe acute respiratory syndrome coronavirus 2 antigen protected against the virus and stimulated the production of highly cross-reactive IgG antibodies against variants XBB1.5 and JN.1. Intriguingly, intramuscular vaccination of the CVP-combined vaccine also elicited the production of IgA antibodies in both nasal wash and bronchoalveolar lavage fluid in mice and cynomolgus monkeys. CVP therefore offers superior adjuvanticity to existing adjuvants and is anticipated to be a safe and effective adjuvant for mucosal vaccines.
Ethical considerations in AI for child health and recommendations for child-centered medical AI
There does not exist any previous comprehensive review on AI ethics in child health or any guidelines for management, unlike in adult medicine. This review describes ethical principles in AI for child health and provides recommendations for child-centered medical AI. We also introduce the Pediatrics EthicAl Recommendations List for AI (PEARL-AI) framework for clinicians and AI developers to ensure ethical AI enabled systems in healthcare for children.
Insights from a century of data reveal global trends in ex situ living plant collections
Ex situ living plant collections play a crucial role in providing nature-based solutions to twenty-first century global challenges. However, the complex dynamics of these artificial ecosystems are poorly quantified and understood, affecting biodiversity storage, conservation and utilization. To evaluate the management of ex situ plant diversity, we analysed a century of data comprising 2.2 million records, from a meta-collection currently holding ~500,000 accessions and 41% of global ex situ species diversity. Our study provides critical insights into the historical evolution, current state and future trajectory of global living collections. We reveal sigmoidal growth of a meta-collection that has reached capacity in both total accessions and total diversity, and identify intrinsic constraints on biodiversity management, including a median survival probability of 15 years. We explore the impact of external constraints and quantify the influence of the Convention on Biological Diversity, which we link to reduced acquisition of wild-origin and internationally sourced material by 44% and 38%, respectively. We further define the impact of these constraints on ex situ conservation but highlight targeted initiatives that successfully mitigate these challenges. Ultimately, our study underscores the urgent need for strategic prioritization and the re-evaluation of ex situ biodiversity management to achieve both scientific and conservation goals.
Short-term efficacy and safety of A-stream glaucoma shunt: a 6-month study
This study evaluated the short-term efficacy and safety of the A-stream Glaucoma Shunt (A-stream; MICROT Inc., Republic of Korea) in patients who completed 6 months of follow-up after implantation.
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