Project description:The Sanaria® PfSPZ Vaccine can confer sterilizing protection against liver stage infection by Plasmodium falciparum (Pf) in malaria naïve individuals. The vaccine consists of aseptically purified irradiated Pf sporozoites. The PfSPZ Vaccine trial in Mali was the first to evaluate the safety and efficacy of this vaccine in a malaria endemic region. Vaccinees received five doses of 2.7 X 105 irradiated sporozoites and the efficacy was measured against naturally occurring Pf Infections in Malian adults during the malaria transmission season.
Project description:BBIBP-CorV, an inactivated vaccine, has demonstrated safety, efficacy, and immunogenicity against COVID-19 in in-vitro studies and clinical trials. This study sought to comprehensively understand the development and duration of virus-specific antibodies and characterize the TCR-β repertoire changes in patients with BBIBP-CorV
Project description:Antivirulence vaccination represents a promising strategy for infection prevention, but achieving both safety and efficacy in toxoid vaccine preparation remains a challenge. Cell membrane-based nanotoxoids offer a safe delivery platform for bacterial virulence factors in antivirulence vaccination, but limited absorption capacity hampers their efficacy. Here, we develop a lipid-based toxoid vaccine platform, PSV-CNP, comprising a CpG-loaded polymeric core coated with phosphatidylcholine/sphingomyelin (PS) liposomes enriched with bacterial virulence factors. By enhancing virulence factor absorption, PSV-CNP elicits robust humoral immunity. In mice, it provides long-lasting protection against methicillin-resistant Staphylococcus aureus (MRSA) and clinically isolated S. aureus (CI-SA), even under immunosuppression. In Bama pigs, PSV-CNP induces strong immune responses and prevents MRSA and CI-SA invasion. Furthermore, PS-liposomes efficiently absorb virulence factors from Pseudomonas aeruginosa (PA), conferring protection against PA infections. This study establishes PS-coated nanoparticles as a broadly applicable, safe, and effective antivirulence toxoid vaccine platform.
Project description:Antivirulence vaccination represents a promising strategy for infection prevention, but achieving both safety and efficacy in toxoid vaccine preparation remains a challenge. Cell membrane-based nanotoxoids offer a safe delivery platform for bacterial virulence factors in antivirulence vaccination, but limited absorption capacity hampers their efficacy. Here, we develop a lipid-based toxoid vaccine platform, PSV-CNP, comprising a CpG-loaded polymeric core coated with phosphatidylcholine/sphingomyelin (PS) liposomes enriched with bacterial virulence factors. By enhancing virulence factor absorption, PSV-CNP elicits robust humoral immunity. In mice, it provides long-lasting protection against methicillin-resistant Staphylococcus aureus (MRSA) and clinically isolated S. aureus (CI-SA), even under immunosuppression. In Bama pigs, PSV-CNP induces strong immune responses and prevents MRSA and CI-SA invasion. Furthermore, PS-liposomes efficiently absorb virulence factors from Pseudomonas aeruginosa (PA), conferring protection against PA infections. This study establishes PS-coated nanoparticles as a broadly applicable, safe, and effective antivirulence toxoid vaccine platform.
Project description:Abdala is a COVID-19 vaccine produced in Pichia pastoris and is based on the receptor-binding domain (RBD) of the SARS-CoV-2 spike. Abdala is currently approved for use in multiple countries with clinical trials confirming its safety and efficacy in preventing severe illness and death. Although P. pastoris is used as an expression system for protein-based vaccines, yeast glycosylation remains largely uncharacterised across immunogens. Here, we characterise N-glycan structures and their site of attachment on Abdala and show how yeast-specific glycosylation decreases binding to the ACE2 receptor and a receptor-binding motif (RBM) targeting antibody compared to the equivalent mammalian-derived RBD. Reduced receptor and antibody binding is attributed to changes in conformational dynamics resulting from N-glycosylation. These data highlight the critical importance of glycosylation in vaccine design and demonstrate how individual glycans can influence host interactions and immune recognition via protein structural dynamics.
Project description:Here we report a cancer vaccine that induced a coordinated attack by diverse T cell and NK cell populations. The vaccine targeted the MICA and MICB (MICA/B) stress proteins expressed by many human cancers due to DNA damage. MICA/B serve as ligands for the activating NKG2D receptor on T cells and NK cells, but tumors evade immune recognition by proteolytic MICA/B cleavage. Vaccine-induced antibodies increased the density of MICA/B proteins on the surface of tumor cells by inhibiting proteolytic shedding, increased presentation of tumor antigens by dendritic cells to T cells, and enhanced the cytotoxic function of NK cells. Importantly, this vaccine maintained efficacy against MHC-I deficient tumors resistant to cytotoxic T cells through the coordinated action of NK cells and CD4 T cells. The vaccine was also efficacious in a clinically important setting: immunization following surgical removal of primary, highly metastatic tumors inhibited the later outgrowth of metastases. This vaccine design enables protective immunity even against tumors with common escape mutations.
Project description:Lung adenocarcinoma (LADC) is the most common subtype of non-small cell lung cancer (NSCLC). One major feature of disease progression is the metastatic spread to the central nervous system (CNS). Treatment regimens for brain metastases are limited, thus distant metastases remain the leading cause of tumour-associated deaths globally. The central aim of this paper was to investigate the differences of LADC and brain metastases with reference to fast and slowly progressing patients. Additionally, we elucidated the differences between patients with single versus multiple brain metastases.
Project description:The primary objective is to compare multiplex immune response signatures following two (primary and a boost) vaccinations with the GSK AS03 adjuvanted H5N1 influenza vaccine or the non-adjuvanted form of the H5N1 influenza vaccine at the 3.75 mcg dose and given 21 days apart and identify differences in very early innate immune responses. These immune signatures will also be correlated with the clinical observations especially safety related local and systemic events.