Vaccine & Gene Therapy Institute

A cytoplasmic motif in HLA-E that drives clathrin-mediated endocytosis and VCP-associated postendocytic trafficking - PubMed Human Leukocyte Antigen E (HLA-E) is a nonclassical MHC class I molecule that exhibits dual immunological functions in regulating natural killer (NK) cells and T cells through unusual trafficking patterns. We previously reported that HLA-E surface expression is low and transient due to its cytoplasm …

Read more at: pubmed.ncbi.nlm.nih.gov/41134633/

In this publication, our Frueh Lab and their contributors, expand on their previous findings related to HLA-E surface expression. This updated study reveals previously unrecognized endosomal trafficking pathways and regulatory mechanisms that distinguish HLA-E from classical HLA class I molecules.

In their recent publication, our Streblow lab with their contributors, explore the emergence of mosquito-borne alphaviruses that cause chronic arthritis or encephalitis and highlight the urgent need for broad-spectrum antiviral therapeutics.

Read more at: pubmed.ncbi.nlm.nih.gov/41090377/

A Proof‐of‐Concept Phase 2a Partly Randomised Study Evaluating Leronlimab in Patients With Presumed Non‐Cirrhotic Metabolic Dysfunction–Associated Steatohepatitis | Request PDF Request PDF | A Proof‐of‐Concept Phase 2a Partly Randomised Study Evaluating Leronlimab in Patients With Presumed Non‐Cirrhotic Metabolic Dysfunction–Associated Steatohepatitis | Chemokine receptor ty...

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www.researchgate.net/publication/...

Leronlimab directly binds the extracellular domains of CCR5, modulates downstream signaling and potentially can slow, reverse, or prevent fibrosis. In this proof‐of‐concept study, our Hansen Lab with contributors, demonstrated that leronlimab has a favorable safety profile and was well tolerated.

Primate resident memory T cells activate humoral and stromal immunity - PubMed CD8⁺ resident memory T (Trm) cells comprise a small population of frontline sentinels compared with the large tissues they surveil, making outsized contributions to immune protection from i...

... and activate diverse host defenses.

Read more at:
pubmed.ncbi.nlm.nih.gov/41092897/

In this recent publication our Bimber, Hansen, Picker lab teams and their contributors demonstrate that systemic vaccination promotes a Trm cell response in barrier compartments and that Trm cells repurpose abundant neighboring stromal, parenchymal, and immune cells to amplify alarm signals...

Liver biopsies obtained throughout SIV infection reveal evolving interferon stimulated protein expression within distinct monocyte/macrophage subsets - PubMed Liver dysfunction is more common and more severe among people with HIV than in the general population. Our previous transcriptomic analysis identified an increased hepatic type-1 interferon (IFN-1) re...

Read the full article here:
pubmed.ncbi.nlm.nih.gov/41004538/

Liver dysfunction is more common and severe among people with HIV than in the general population. In this recent publication, our Burwitz affiliate lab explores the correlation between different cell types in the IFN-1 response, focusing on macrophage subsets during the acute phase of SIV infection.

Integrated lipidomic and proteomic profiling reveals metabolic network disruption by SARS-CoV-2 variants - PubMed The rapid evolution of SARS-CoV-2 has produced myriad viral strains with increasing transmissibility and capacity for immune evasion. While effective vaccination campaigns have reduced the fatalities ...

...of the enzymes involved in their biosynthesis.

Read the full article here: pubmed.ncbi.nlm.nih.gov/40659247/

In their recent publication, our Tafesse affiliate lab with their contributors, explore SARS-CoV-2 and whether the patterns of host lipid rewiring remained consistent across variants and whether the changes in the abundance of lipid classes are related to changes in the expression...

Novel tricycle expanded purine nucleosides with pan-viral activity - PubMed A series of thiophene-expanded tricyclic nucleosides featuring modifications not previously investigated, including sugar and nucleobase modifications, were synthesized as potential antiviral therapeu...

...their potential antiviral activity, as typically prodrugs increase solubility and delivery. Additional studies are underway to elucidate the mechanism of action of these analogues.

Read the full article here: pubmed.ncbi.nlm.nih.gov/40939252/

In collaboration with Dr. Seley-Radtke’s group at the University of Maryland, our Hirsch lab has contributed to a study identifying a new series of thiophene-expanded tricyclic nucleosides as potential antiviral therapeutics. In addition, their corresponding prodrugs were also pursued to probe...

Targeting MHC-E as a new strategy for vaccines and immunotherapeutics - Nature Reviews Immunology The dual nature of non-polymorphic MHC-E as a ligand for innate receptors and as an antigen-presenting protein raises the possibility of new, universally effective vaccines and immunotherapies for inf...

In addition, MHC-E has a number of fascinating functions in regulating immunity that have many possible applications for the development of vaccines and immunotherapies against infectious diseases and cancer." -Klaus Früh, Ph.D.

Here is a link to the full text:
www.nature.com/articles/s41...

MHC-E is a non-classical MHC class I protein that has been studied for many years by the Oxford group and that we stumbled upon in our research on using cytomegalovirus as a novel vaccine vector. We found that T cells targeting MHC-E might be the key to the development of an AIDS vaccine
(continued)

"Everything you always wanted to know about MHC-E, but were afraid to ask.... is covered in this Nature Review, the result of a team effort together with Louis Picker here at OHSU and Andrew McMichael, Geraldine Gillespie and Persephone Borrow from University of Oxford.
(continued)

Impact of obesity on the gut microbiome and inflammatory markers during SIV infection and antiretroviral therapy - PubMed Dysbiosis and impaired gut barrier integrity contribute to chronic immune activation associated with both obesity and HIV infection. Given the increased incidence of obesity in people living with HIV,...

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pubmed.ncbi.nlm.nih.gov/40862619/

Our Sacha Affiliate Lab, with their contributors, have recently published a new study where they explored the impact of obesity on the gut microbiome and microbial translocation (MT) biomarkers during HIV infection and antiretroviral therapy (ART). Amazing work done by all!

Glycoprotein L–deleted single-cycle rhesus cytomegalovirus vectors elicit MHC-E–restricted CD8+ T cells that protect against SIV Abstract. Strain 68-1 rhesus CMV (RhCMV) vectors induce immune responses that mediate early, complete replication arrest of SIV infection in ∼60% of vaccin

... facilitates the development of safe and efficacious vaccines in humans.

Read the full article here:
academic.oup.com/jimmunol/art...

This study by Dr Hansen et al. demonstrates that CMV-based vaccines protect against SIV even when highly attenuated by deleting a glycoprotein essential for CMV entry. The remarkable ability to uncouple viral spreading from its immunogenicity is a unique feature of CMV based vectors and...

(PDF) An immune-focused supplemental alignment pipeline captures information missed from dominant single-cell RNA-seq analyses, including allele-specific MHC-I regulation PDF | Introduction RNA sequencing (RNA-seq) can measure whole transcriptome gene expression from tissues or even individual cells, providing a powerful... | Find, read and cite all the research you ne...

Incredible work by the Bimber, Okoye, Sacha, Estes, Axthelm, Streblow, Hansen, Picker lab teams with their contributors.

Read the full article here:

www.researchgate.net/publication/...

This recently published paper titled, "An immune-focused supplemental alignment pipeline captures information missed from dominant single-cell RNA-seq analyses, including allele-specific MHC-I regulation" showcases an incredible collaboration between between the VGTI Labs and Affiliate Labs.

The TLR7/8 agonist INI-4001 enhances the immunogenicity of a Powassan virus-like-particle vaccine - PubMed Powassan virus (POWV) is a pathogenic tick-borne flavivirus that causes fatal neuroinvasive disease in humans. There are currently no approved therapies or vaccines for POWV infection. Here, we develo...

Read the full article here:
pubmed.ncbi.nlm.nih.gov/40670406/

There are currently no approved therapies or vaccines for Powassan virus infection. In this recent publication, our Hirsch lab and their contributors, developed a POW virus-like particle (POW-VLP) based vaccine adjuvanted with the novel synthetic Toll-like receptor 7/8 agonist INI-4001.

Cytomegalovirus latency-the sum of subtleties - PubMed Human cytomegalovirus (HCMV) is a betaherpesvirus, which, like all herpesviruses, establishes a life-long latent infection while retaining the ability to reactivate its replicative program. While HCMV...

...corresponding orthologs to HCMV.

Read the full article here:
pubmed.ncbi.nlm.nih.gov/40736257/

Our Hancock, Caposio, and Streblow Labs with their contributors, have recently published this review on the current understanding of HCMV latency. They focus on cross-cutting principles derived collectively from in vitro experimental culture models and in vivo animal models using the...

OHSU researchers have identified a gene that plays a crucial role in the brain's ability to form #myelin, potentially opening new doors to treatments for a rare childhood disorder and more common diseases such as #MultipleSclerosis. www.miragenews.com/gene-linked-...

Enhanced interpretation of immune cell phenotype and function through a rhesus macaque single-cell atlas - PubMed Single-cell RNA sequencing (scRNA-seq) allows cell classification using genome-wide transcriptional state; however, high-dimensional transcriptomic profiles, and the unsupervised analyses employed to ...

...surface protein and marker genes as ground truth.

Read the full article here:
pubmed.ncbi.nlm.nih.gov/40233746/

In this incredible collaboration our Estes, Okoye, Axthelm, Hansen, Picker, Bimber affiliate and lab teams— present the RIRA, the first immune-focused macaque single-cell multi-tissue atlas. They contrasted transcriptional profiles against immune lineages, using...

Prophylactic and therapeutic neutralizing monoclonal antibody treatment prevents lethal yellow fever infection - PubMed Yellow Fever virus (YFV) infection is fatal in 5-10% of the 200,000 yearly cases. There is currently no available antiviral treatment. We showed previously that administration of 50 mg/kg of a YFV-spe...

Read the full article here:
pubmed.ncbi.nlm.nih.gov/40663406/