A5077241520- HIV Research and Treatment
- Immunotherapy and Immune Responses
- Immune Cell Function and Interaction
- vaccines and immunoinformatics approaches
- RNA Interference and Gene Delivery
- Viral Infections and Vectors
- Hepatitis B Virus Studies
- Mosquito-borne diseases and control
- Respiratory viral infections research
- HIV/AIDS drug development and treatment
- Influenza Virus Research Studies
- Immune Response and Inflammation
- Viral Infections and Outbreaks Research
- Animal Virus Infections Studies
- Virus-based gene therapy research
- Transgenic Plants and Applications
- T-cell and B-cell Immunology
- HIV/AIDS Research and Interventions
- Viral gastroenteritis research and epidemiology
- Herpesvirus Infections and Treatments
- RNA and protein synthesis mechanisms
- interferon and immune responses
- Advanced biosensing and bioanalysis techniques
- Microbial Inactivation Methods
- Cytomegalovirus and herpesvirus research
Karolinska Institutet
2010-2020
Public Health Agency of Sweden
2005-2019
University of North Carolina at Chapel Hill
2005-2007
Swedish Institute
2000-2006
Therapeutic application of the recently discovered small interfering RNA (siRNA) gene silencing phenomenon will be dependent on improvements in molecule bio-stability, specificity and delivery. To address these issues, we have systematically modified siRNA with synthetic RNA-like high affinity nucleotide analogue, Locked Nucleic Acid (LNA). Here, show that incorporation LNA substantially enhances serum half-life siRNA's, which is a key requirement for therapeutic use. Moreover, provide...
Background. A human immunodeficiency virus (HIV) vaccine that limits disease and transmission is urgently needed. This clinical trial evaluated the safety immunogenicity of an HIV combines a plasmid-DNA priming modified vaccinia Ankara (MVA) boosting vaccine.
Chikungunya virus (CHIKV) is rapidly spreading across the globe, and millions are infected. Morbidity due to this a serious threat public health, but at present, there no vaccine against debilitating disease. We have recently developed number of candidates, here we evaluated 3 them in nonhuman primate model. A single immunization with an attenuated strain CHIKV (Δ5nsP3), homologous prime-boost DNA-launched RNA replicon encoding envelope proteins (DREP-E), DREP-E prime followed by recombinant...
RNA-based vaccines represent an interesting immunization modality, but suffer from poor stability and a lack of efficient clinically feasible delivery technologies. This study evaluates the immunogenic potential naked in vitro transcribed Semliki Forest virus replicon RNA (RREP) delivered intradermally combination with electroporation. Replicon-immunized mice showed strong cellular humoral response, contrary to immunized regular mRNA. RREP-elicited induction interferon-γ secreting CD8+ T...
Significance Influenza A virus infections are risk factors for narcolepsy, a disease in which autoimmunity has been implicated. We tested experimentally whether influenza could be causally related to narcolepsy. found that mice infected with H1N1 strain developed over time sleep–wake changes described murine models of narcolepsy and patients. In the brain, orexin/hypocretin-producing neurons, destroyed human other cells distributed sleep–wake-regulating neuronal network. The findings,...
Abstract A novel T‐cell vaccine strategy designed to deal with the enormity of HIV‐1 variation is described and tested for first time in macaques inform complement approaching clinical trials. immunogen HIVconsv, which directs vaccine‐induced responses most conserved regions HIV‐1, proteome thus both targets diverse clades population reduces chance escape infected individuals, was delivered using six different modalities: plasmid DNA (D), attenuated human (A) chimpanzee (C) adenoviruses,...
Gene vaccination encounters problems different from those of gene therapy since both a short half-life the and strong immune response to product are desirable. We have evaluated DNA vaccine consisting seven plasmids encoding nine HIV-1 proteins. Using needle-free delivery device, Biojector, together with recombinant mouse GM-CSF, this induced gp160 Env- p24 Gag-specific cellular humoral responses in mice. The rGM-CSF was crucial for inducing antibodies antigen-specific CD8(+) T cell against...
DNA vaccination is an attractive approach to induce antigen-specific cytotoxic CD8(+) T lymphocytes (CTLs), which can mediate protective antitumor immunity. The potency of vaccines encoding weakly immunogenic tumor-associated antigens (TAAs) be enhanced by codelivering gene-encoded adjuvants. Pattern recognition receptors (PRRs) that sense intracellular could potentially used harness intrinsic immune-stimulating properties plasmid vaccines. Consequently, the cytosolic sensor, DNA-dependent...
ABSTRACT Vaccination using “naked” DNA is a highly attractive strategy for induction of pathogen-specific immune responses; however, it has been only weakly immunogenic in humans. Previously, we constructed DNA-launched Semliki Forest virus replicons (DREP), which stimulate pattern recognition receptors and induce augmented responses. Also, vivo electroporation was shown to enhance responses induced by conventional vaccines. Here, combine these two approaches show that increases CD8 + T cell...
Cervical cancer develops as a result of infection with high-risk human papillomavirus (HPV) through persistent expression early proteins E6 and E7. Our group pioneered recombinant viral vector system based on Semliki Forest virus (SFV) for vaccination against cervical cancer. The most striking benefit this alphavirus vector-based vaccine platform is its high potency. DNA vaccines the other hand, have major advantage respect to ease production. In study, benefits associated both SFV-based...
Zaire and Sudan ebolavirus species cause a severe disease in humans nonhuman primates (NHPs) characterized by high mortality rate. There are no licensed therapies or vaccines against Ebola virus (EVD), the recent 2013 to 2016 outbreak West Africa highlighted need for EVD-specific medical countermeasures. Here, we generated head-to-head immunogenicity efficacy of five vaccine candidates (EBOV) (SUDV) based on highly attenuated poxvirus vector modified vaccinia Ankara (MVA) expressing either...
A novel genetic vaccine that is based on a Venezuelan equine encephalitis virus (VEE) replicon launched from plasmid DNA described. The encodes VEE under the transcriptional control of cytomegalovirus immediate-early promoter (VEE DNA). consistently expressed 3- to 15-fold more green fluorescent protein in vitro than did conventional vaccine. Furthermore, transfection with DNA-launched induced apoptosis and type I interferon production. Inoculation mice encoding human immunodeficiency 1...
ABSTRACT Alphavirus replicons are potent inducers of CD8 + T cell responses and thus constitute an attractive vaccine vector platform for developing novel vaccines. However, the kinetics memory phenotype induced by alphavirus not well characterized. Furthermore, little is known how priming with affects booster immune other modalities. We demonstrate here that a single immunization replicon, administered as viral particles or naked DNA, antigen-specific response had sharp peak, followed rapid...
Vaccination with DNA is an attractive strategy for induction of pathogen-specific T cells and antibodies. Studies in humans have shown that vaccines are safe, but their immunogenicity needs further improvement. As a step towards this goal, we previously demonstrated increased the use alphavirus DNA-launched replicon (DREP) vector compared to conventional vaccines. In study, investigated effect varying dose number administrations DREP when given as prime prior heterologous boost poxvirus...
The results presented here are from the preclinical evaluation in BALB/c mice of a DNA prime/modified vaccinia virus Ankara (MVA) boost multi-gene multi-subtype human immunodeficiency virus-1 (HIV-1) vaccine intended for use humans. plasmid was delivered intradermally using Biojector, and MVA intramuscularly by needle. This combination recombinant proved to induce extraordinarily strong cellular responses, with more than 80% CD8(+) T cells specific HIV-1 antigens. Furthermore, we show that...
There are currently no licensed therapeutic treatment or preventive vaccines against Ebolavirus disease, and the 2013-2016 West African outbreak of disease spread rapidly resulted in almost 30,000 cases more than 11,000 deaths. However, devastating has spurred development novel vaccines. Here, we demonstrate that alphavirus-based DNA-launched self-replicating RNA replicon (DREP) encoding either glycoprotein (GP) gene co-expressing GP VP40 genes Sudan Zaire immunogenic mice inducing both...
We describe a novel vaccine platform that can generate protective immunity to chikungunya virus (CHIKV) in C57BL/6J mice after single immunization by employing an infectious RNA (iRNA), which upon introduction into host cell launches attenuated virus. and others have previously reported engineered deletion of 183 nucleotides the nsP3 gene attenuates reduces vivo viral replication viremia challenge mice, macaques man. Here, we demonstrated vitro transfection iRNA carrying generated viruses,...
Hepatitis C is a liver disease caused by the hepatitis virus (HCV) affecting 71 million people worldwide with no licensed vaccines that prevent infection. Here, we have generated four novel alphavirus-based DNA-launched self-amplifying RNA replicon (DREP) expressing either structural core-E1-E2 or nonstructural p7-NS2-NS3 HCV proteins of genotype 1a placed under control an alphavirus promoter, without alphaviral translational enhancer (grouped as DREP-HCV DREP-e-HCV, respectively). DREP...