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: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: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.
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:Brucellosis, caused by Brucella spp, is an important zoonotic disease leading to enormous economic losses in livestock and posing great threat to public health worldwide. The live attenuated Brucella suis (B. suis) strain S2 is a safe and effective vaccine, and it is most widely used in animals in China. However, S2 vaccination in animals may raise debates and concerns in terms of safety to primates, particularly human. In this study, using cynomolgus monkey as an animal model, we evaluated the safety of the S2 vaccine strain on primate, in addition, we performed transcriptome analysis to determine gene expression profiling on cynomolgus monkeys immunized with the S2 vaccine. Our results suggested that the S2 vaccine was safe to cynomolgus monkeys. Transcriptome analysis identified 663 differentially expressed genes (DEGs), of which 348 were significantly up-regulated and 315 were remarkably down-regulated. Gene Ontology (GO) classification and KEGG pathway analysis indicated that these DEGs were involved in various biological processes, including chemokine signaling pathway, actin cytoskeleton regulation, defense response, immune system processing, and type I interferon signaling pathway. The molecular functions of the DEGs mainly comprised of 2'-5'-oligoadenylate synthetase activity, double-stranded RNA binding and actin binding. Moreover, the cellular components of these DEGs included integrin complex, myosin II complex and blood microparticle. Our findings alleviate the concerns in safety of the S2 vaccine on primates and provide genetic basis of mammalian host response and gene regulation after vaccination with the S2 vaccine.
Project description:The time course of whole blood gene expression was measured after the fourth immunisation at month 6 in participants who had been randomised into vaccine or placebo group 1 of the clinical protocol HVTN087 - A phase 1 trial to evaluate the safety, tolerability, and immunogenicity of an IL-12 pDNA enhanced HIV-1 multi-antigen pDNA vaccine delivered intramuscularly with electroporation, with an HIV-1 rVSV vaccine boost, in healthy HIV-uninfected adult participants (NCT01578889).
Project description:Background
Ipilimumab improves survival for patients with metastatic malignant melanoma. Combining a therapeutic cancer vaccine with ipilimumab may increase efficacy by providing enhanced anti-tumor immune responses. UV1 consists of three synthetic long peptides from human telomerase reverse transcriptase (hTERT). These peptides comprise epitopes recognized by T cells from cancer patients experiencing long-term survival following treatment with a first-generation hTERT vaccine, and generate long-lasting immune responses in cancer patients when used as monotherapy. The objective of this trial was to investigate the safety and efficacy of combining UV1 with ipilimumab in metastatic melanoma.
Patients and methods
In this phase I/IIa, single center trial [NCT02275416], patients with metastatic melanoma received repeated UV1 vaccinations, with GM-CSF as an adjuvant, in combination with ipilimumab. Patients were evaluated for safety, efficacy and immune response. Immune responses against vaccine peptides were monitored in peripheral blood by measuring antigen-specific proliferation and IFN-γ production.
Results
Twelve patients were recruited. Adverse events were mainly diarrhea, injection site reaction, pruritus, rash, nausea and fatigue. Ten patients showed a Th1 immune response to UV1 peptides, occurring early and after few vaccinations. Three patients obtained a partial response and one patient a complete response. Overall survival was 50% at 5 years.
Conclusion
Treatment was well tolerated. The rapid expansion of UV1-specific Th1 cells in the majority of patients indicates synergy between UV1 vaccine and CTLA-4 blockade. This may have translated into clinical benefit, encouraging the combination of UV1 vaccination with standard of care treatment regimes containing ipilimumab/CTLA-4 blocking antibodies.