2019-01-01·Transboundary and emerging diseases1区 · 农林科学
Identification and characterization of vaccine candidates against Hyalomma anatolicum-Vector of Crimean-Congo haemorrhagic fever virus.
1区 · 农林科学
作者: Haranahally Vasanthachar Manjunathachar ; Binod Kumar ; Buddhi Chandrasekaran Saravanan ; Suman Choudhary ; Ashok K Mohanty ; Gaurav Nagar ; Gajanan Chigure ; Gandham V P P S Ravi Kumar ; José de la Fuente ; Srikant Ghosh
Crimean-Congo haemorrhagic fever (CCHF) is a tick borne viral disease reported from different parts of the world. The distribution of the CCHF cases are linked with the distribution of the principal vector, Hyalomma anatolicum in the ecosystem. Presently, vector control is mainly dependent on repeated application of acaricides, results in partial efficacy and generated acaricide resistant tick strains. Amongst the different components of integrated management programme, immunization of hosts is considered as one of the sustainable component. To restrict CCHF virus spreading, use of anti-Hyalomma vaccines appears as a viable solution. Accordingly, present study was under taken to characterize and evaluate vaccine potential of two conserved molecules, ferritin2 (FER2) and tropomyosin (TPM). Silencing of the genes conferred a cumulative reduction (rejection + unable to engorge) of 61.3% in FER2 and 70.2% in TPM respectively. Furthermore, 44.2% and 72.7% reduction in engorgement weight, 63.6% and 94.9% reduction in egg masses in FER2 and TPM silenced ticks in comparison to LUC-control group was recorded. The recombinant protein, rHaFER2 was characterized as 35 kDa protein with pI of 5.84 and possesses iron binding domains. While rHaTPM is a 51kDa protein with pI of 4.94 having calcium binding domains. Immunization of cross-bred calves by rHaFER2 conferred 51.7% and 51.2% protection against larvae and adults of H. anatolicum challenge infestations. While rHaTPM conferred 63.7% and 66.4% protection against larvae and adults infestations, respectively. The results were comparable with the data generated by RNAi and it clearly showed the possibility for the development of anti-hyalomma vaccine to manage CCHF virus and Theileria annulata infection in human and animals.
2016-01-01·PLoS One3区 · 综合性期刊
Regulation of Gag- and Env-specific CD8+ T cell responses in ART-Naive HIV-infected patients: potential implications for individualized immunotherapy
3区 · 综合性期刊
作者: Prebensen, Christian ; Lind, Andreas ; Dyrhol-Riise, Anne-Ma ; Kvale, Dag
Strategies to develop a functional cure for HIV infection will likely require boosting of effector T cell responses to eliminate reactivated, latently infected cells. We have recently explored an assay for assessing antigen-specific regulation of T cell proliferation, which was related to clinical progression in untreated patients and to vaccine efficacy in two trials of therapeutic Gag-based vaccines. We here expand the same assay to further investigate regulation mediated by various inhibitory pathways. Peripheral blood mononuclear cells from 26 asymptomatic HIV-infected, antiretroviral therapy-naïve patients were stimulated with Gag and Env overlapping peptide panels for 5 days. Monoclonal antibodies (mAbs) blocking inhibitory mediators interleukin (IL) 10, transforming growth factor (TGF) β, programmed death ligand (PD-L) 1 and herpes virus entry mediator (HVEM) were added to parallel cultures. Functional T cell regulation (FTR) was defined as the difference in proliferation between stimulated cultures with and without blocking mAbs. FTR was detected in 54% of patients. Blockade of IL-10/PD-L1 and IL10/TGF-β detected all cases with Gag- and Env-associated FTR, respectively. In accordance with previous findings, isolated Env FTR was associated with higher plasma HIV RNA and lower CD4 counts, while patients with both Gag and Env FTR also had higher Gag- and Env-specific proliferative CD8+ T cell responses. There was no association between FTR and frequencies of activated regulatory T cells. In conclusion, we observed substantial heterogeneity in FTR between patients, inhibitory pathways and HIV antigens. FTR may help to individualize immunomodulation and warrants further assessment in clinical immunotherapy trials.
2012-01-01·PLoS One3区 · 综合性期刊
Protective antibody and CD8+ T-cell responses to the Plasmodium falciparum circumsporozoite protein induced by a nanoparticle vaccine
3区 · 综合性期刊
作者: Kaba, Stephen A. ; McCoy, Margaret E. ; Doll, Tais A. P. F. ; Brando, Clara ; Guo, Qin ; Dasgupta, Debleena ; Yang, Yongkun ; Mittelholzer, Christian ; Spaccapelo, Roberta ; Crisanti, Andrea ; Burkhard, Peter ; Lanar, David E.
The worldwide burden of malaria remains a major public health problem due, in part, to the lack of an effective vaccine against the Plasmodium falciparum parasite. An effective vaccine will most likely require the induction of antigen specific CD8(+) and CD4(+) T-cells as well as long-lasting antibody responses all working in concert to eliminate the infection. We report here the effective modification of a self-assembling protein nanoparticle (SAPN) vaccine previously proven effective in control of a P. berghei infection in a rodent model to now present B- and T-cell epitopes of the human malaria parasite P. falciparum in a platform capable of being used in human subjects.
To establish the basis for a SAPN-based vaccine, B- and CD8(+) T-cell epitopes from the P. falciparum circumsporozoite protein (PfCSP) and the universal CD4 T-helper epitope PADRE were engineered into a versatile small protein (∼125 amino acids) that self-assembles into a spherical nanoparticle repetitively displaying the selected epitopes. P. falciparum epitope specific immune responses were evaluated in mice using a transgenic P. berghei malaria parasite of mice expressing the human malaria full-length P. falciparum circumsporozoite protein (Tg-Pb/PfCSP). We show that SAPN constructs, delivered in saline, can induce high-titer, long-lasting (1 year) protective antibody and poly-functional (IFNγ(+), IL-2(+)) long-lived central memory CD8(+) T-cells. Furthermore, we demonstrated that these Ab or CD8(+) T-cells can independently provide sterile protection against a lethal challenge of the transgenic parasites.
The SAPN construct induces long-lasting antibody and cellular immune responses to epitope specific sequences of the P. falciparum circumsporozoite protein (PfCSP) and prevents infection in mice by a transgenic P. berghei parasite displaying the full length PfCSP.
- Preclinical data showing the rationale for two new pipeline candidates targeting the immunosuppressive effects of Arginase-1 (ARG1) and Transforming Growth Factor Beta 1 (TGFb1) were presented in two posters
NEW YORK, Nov. 09, 2022 (GLOBE NEWSWIRE) -- IO Biotech (Nasdaq: IOBT), IO Biotech, a clinical-stage biopharmaceutical company developing novel, immune-modulating anti-cancer therapies based on its proprietary T-win® technology, today announced details of the invited oral presentation and two poster presentations at the Society for Immunotherapy of Cancer’s (SITC) 37th Annual Meeting.
Information for the invited oral presentation:
Title: Utilizing Tumor Microenvironment Antigens for Immune Modulatory Vaccines
Session: Concurrent Session 119 – Vaccines: In Situ Agents and Novel Systemic Approaches
Presenter: Mads Hald Andersen, Ph.D. – Professor and Director of Center for Cancer Immune Therapy at Herlev University Hospital, IO Biotech Founder and Scientific Advisor
Date: Thursday, November 10, 2022
Location and time: TBD – 6:25 p.m. EST
“We are pleased that Dr. Andersen has been invited to SITC to give an overview of our Phase 1/2 MM1636 study at SITC and are very encouraged that the long-term follow up data confirm the earlier results reported from this study in front-line PD-1 naïve metastatic melanoma patients,” said Mai-Britt Zocca, Ph.D., President and Chief Executive Officer of IO Biotech. “We are also thrilled to share, for the first time, preclinical data from the next two candidates in our pipeline that target ARG1 and TGFβ1, immunosuppressive antigens found in the tumor microenvironment (TME).”
Dr. Zocca continued, “Based on the promising clinical results of our lead asset, IO102-103, which dually targets and disrupts immunosuppressive antigens indoleamine 2,3-dioxygenase (IDO) and anti-programmed death ligand 1 (PD-L1), we believe that targeting suppressive antigens can not only better allow T-cells to directly attack tumor cells, but also modulate the TME as an immunotherapeutic approach. We see the potential of these two new candidates to build on the strength of our T-win® platform and a path forward for Investigational New Drug filings. We look forward to providing additional updates on both our Phase 3 trial with IO102-103 in combination with pembrolizumab for metastatic melanoma and our Phase 2 basket trial in solid tumors in the coming weeks and months.”
Highlights from the two preclinical poster presentations include:
Title: Modulating the TME by targeting TGFb1 with vaccine-induced immune responses
Abstract Number: 1182
Presenter: Brian Weinert, Ph.D., Principal Scientist IO Biotech
Date: Friday, November 11, 2022
Location and time: Poster Hall C Poster Hall Hours: 9 a.m.– 8:30 p.m. EST
Transforming Growth Factor Beta 1 (TGFb1) is a major immune suppressive element in the tumor microenvironment (TME) of most solid tumors. It is implicated in antagonizing the efficacy of various immune oncology therapies. Developing selective and efficacious modulators of the pathway is an ongoing challenge in the field. IO Biotech has deployed its unique approach to modulate TGFb1 activity in the TME, and the poster details the identification and characterization of highly selective TGFb1 peptide vaccines. These peptides were shown to induce potent and selective immune responses (versus TGFb2 and TGFb3). Murine TGFb1 peptide vaccines were also identified and characterized, and functional activity was preliminarily demonstrated in a relevant murine tumor mouse model (MC38). Translational work detailing content and identity of cells expressing TGFb1 and other immune suppressive antigens in the TME provided the biological rationale to target TGFb1 via a vaccine approach individually and in combination with other TME targets. These preclinical data support further development of a TGFβ1 vaccine as a TME targeted approach for the treatment of a wide range of cancers.
Title: An Arginase-1 peptide-based vaccine is an exciting approach to modulate the TME and drive efficacy in preclinical tumor models
Abstract Number: 1440
Presenter: Marion Chapellier, Ph.D., Senior Scientist IO Biotech
Date: Friday, November 11, 2022
Location and time: Poster Hall C Poster Hall Hours: 9 a.m.– 8:30 p.m. EST
Arginase-1 (ARG1) regulates immune escape of tumor cells through various mechanisms in the tumor microenvironment (TME). It is being targeted experimentally in the clinic, but selective and efficacious inhibitors of ARG1 remain elusive. IO Biotech has shown that vaccination against TME targets is an exciting new therapeutic approach and has previously identified and characterized selective ARG1 peptide vaccines. The poster highlights translational data to guide clinical development of the vaccine in the relevant cancer indications and provides a biological rationale to combine an ARG1 vaccine with other TME vaccines (IDO1/PD-L1). In addition, in vivo data demonstrated functional efficacy of the murine ARG1 vaccine in two ARG1 expressing mouse cancer models in combination with other TME vaccines. These preclinical data support further development of an ARG1 vaccine as a TME vaccine targeted approach in combination with an IDO/PD-L1 vaccine for the treatment of a wide range of solid cancers and we anticipate an IND filing for IO112 (ARG1 vaccine) in 2023.
Established in 1984, the Society for Immunotherapy of Cancer (SITC) is a nonprofit organization of medical professionals dedicated to improving cancer patient outcomes by advancing the development, science and application of cancer immunotherapy and tumor immunology. SITC is comprised of influential basic and translational scientists, practitioners, health care professionals, government leaders and industry professionals around the globe. Through educational initiatives that foster scientific exchange and collaboration among leaders in the field, SITC aims to one day make the word “cure” a reality for cancer patients everywhere. Learn more about SITC at sitcancer.org
About IO Biotech
IO Biotech is a clinical-stage biopharmaceutical company developing novel, immune-modulating cancer therapies based on its T-win® technology platform. The T-win® platform is a novel approach to cancer immunotherapy designed to activate naturally occurring T cells to target immunosuppressive mechanisms. IO Biotech is advancing in clinical studies its lead immuno-oncology candidate, IO102-IO103, targeting IDO and PD-L1, and through preclinical development its other pipeline candidates. IO Biotech is headquartered in Copenhagen, Denmark, with its United States headquarters in New York, New York.
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