Recombinant influenza virus vaccines based on hemagglutinin (HA) hold the potential to accelerate production timelines and improve efficacy relative to traditional egg-based platforms. Here, we assess a vaccine adjuvant system comprised of immunogenic liposomes that spontaneously convert soluble antigens into a particle format, displayed on the bilayer surface. When trimeric H3 HA was presented on liposomes, antigen delivery to macrophages was improved in vitro, and strong functional antibody responses were induced following intramuscular immunization of mice. Protection was conferred against challenge with a heterologous strain of H3N2 virus, and naive mice were also protected following passive serum transfer. When admixed with the particle-forming liposomes, immunization reduced viral infection severity at vaccine doses as low as 2 ng HA, highlighting dose-sparing potential. In ferrets, immunization induced neutralizing antibodies that reduced the upper respiratory viral load upon challenge with a more modern, heterologous H3N2 viral strain. To demonstrate the flexibility and modular nature of the liposome system, 10 recombinant surface antigens representing distinct influenza virus strains were bound simultaneously to generate a highly multivalent protein particle that with 5 ng individual antigen dosing induced antibodies in mice that specifically recognized the constituent immunogens and conferred protection against heterologous H5N1 influenza virus challenge. Taken together, these results show that stable presentation of recombinant HA on immunogenic liposome surfaces in an arrayed fashion enhances functional immune responses and warrants further attention for the development of broadly protective influenza virus vaccines.
A self-assembling influenza virus vaccine platform that seamlessly converts soluble antigens into nanoparticles is demonstrated with various H1N1 and H3N2 influenza antigens to protect mice against influenza virus challenge following intranasal vaccination. Mucosal immune responses following liposome delivery to lung antigen-presenting cells are demonstrated.
Background: Thymic Neuroendocrine Tumor (TNET) is a rare clinical condition with approximate incidence rate of 2-5%. Carcinoid tumor of thymus with Cushing's syndrome (CS) is also a rare co-morbid condition. Case information: Here we report a case of a 22-year-old gentleman presented with uncommon features suggestive of CS. He was evaluated and diagnosed with ectopic Adrenocorticotropic hormone (ACTH)-dependent CS due to a TNET. Results: Extensive thymectomy was performed and histopathology confirmed the diagnosis of thymic carcinoma with neuroendocrine differentiation and local and pericardial invasion. Conclusion: Thymic carcinomas may present with symptoms due to mass effect but Cushing syndrome is the most common endocrine manifestation of these tumors. Surgery is the most effective treatment of thymic carcinoma, although chemotherapy and radiotherapy also have been reported to be effective in some cases.
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