MIP3α-Rel intranasal DNA vaccination induces reactive T-cell infiltration into the lungs of mice and macaques.

Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis (TB), is the leading cause of mortality due to a single infectious organism. While generally curable, TB requires a lengthy and complex antibiotic regimen, due in large part to persistent bacteria that survive antibiotic exposure. Rel is the primary enzyme regulating the stringent response, which contributes to Mtb persistence.

MIP-3α-antigen fusion DNA vaccine enhances sex differences in tuberculosis model and alters dendritic cell activity early post vaccination.

Tuberculosis disease (TB) caused by Mycobacterium tuberculosis (Mtb) bacteria remains a major cause of global morbidity and mortality. Efforts to control TB are hampered by the lengthy and cumbersome treatment required to eradicate the Mtb infection. Bacterial persistence during exposure to bactericidal antibiotics is at least partially mediated by the bacterial stringent response enzyme, Rel.

Novel Vaccines Targeting the Highly Conserved SARS-CoV-2 ORF3a Ectodomain Elicit Immunogenicity in Mouse Models.

Background: The majority of antigen-based SARS-CoV-2 (SCV2) vaccines utilized in the clinic have had the Spike protein or domains thereof as the immunogen. While the Spike protein is highly immunogenic, it is also subject to genetic drift over time, which has led to a series of variants of concern that continue to evolve, requiring yearly updates to the vaccine formulations. In this study, we investigate the potential of the N-terminal ectodomain of the ORF3a protein encoded by the gene of SCV2 to be an evolution-resistant vaccine antigen.

MIP-3α-antigen fusion DNA vaccine enhances sex differences in tuberculosis model and alters dendritic cell activity early post vaccination.

Background: Tuberculosis (TB) remains a major cause of global morbidity and mortality. Efforts to control TB are hampered by the lengthy and cumbersome treatment required to eradicate the infection. Bacterial persistence during exposure to bactericidal antibiotics is at least partially mediated by the bacterial stringent response enzyme, Rel.

Therapeutic DNA Vaccine Targeting Persisters Shortens Curative Tuberculosis Treatment.

Unlabelled: Mtb) is one of the leading infectious causes of death worldwide. There is no available licensed therapeutic vaccine that shortens active tuberculosis (TB) disease drug treatment and prevents relapse, despite the World Health Organization's calls. Here, we show that an intranasal DNA vaccine containing a fusion of the stringent response gene with the gene encoding the immature dendritic cell-targeting chemokine, MIP-3α/CCL20, shortens the duration of curative TB treatment in immunocompetent mice.

MIP3α-Rel intranasal DNA vaccination induces reactive T-cell infiltration into the lungs in mice and macaques.

(Mtb), the causative agent of tuberculosis (TB), is the leading cause of mortality due to a single infectious organism. While generally curable, TB requires a lengthy and complex antibiotic regimen, due in large part to bacteria that can shift to a persistent state in the presence of antibiotic pressure. Rel is the primary enzyme regulating the stringent response, which contributes to the metabolic shift of Mtb to a persistent state.

A SARS-CoV-2 RBD vaccine fused to the chemokine MIP-3α elicits sustained murine antibody responses over 12 months and enhanced lung T-cell responses.

Background: Previous studies have demonstrated enhanced efficacy of vaccine formulations that incorporate the chemokine macrophage inflammatory protein 3α (MIP-3α) to direct vaccine antigens to immature dendritic cells. To address the reduction in vaccine efficacy associated with a mutation in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mutants, we have examined the ability of receptor-binding domain vaccines incorporating MIP-3α to sustain higher concentrations of antibody when administered intramuscularly (IM) and to more effectively elicit lung T-cell responses when administered intranasally (IN).

Methods: BALB/c mice aged 6-8 weeks were immunized intramuscularly or intranasally with DNA vaccine constructs consisting of the SARS-CoV-2 receptor-binding domain alone or fused to the chemokine MIP-3α.

TGF-β2 enhances expression of equine bone marrow-derived mesenchymal stem cell paracrine factors with known associations to tendon healing.

Background: Mesenchymal stem cells (MSCs) secrete paracrine factors and extracellular matrix proteins that contribute to their ability to support tissue healing and regeneration. Both the transcriptome and the secretome of MSCs can be altered by treating the cells with cytokines, but neither have been thoroughly investigated following treatment with the specific cytokine transforming growth factor (TGF)-β2.

Methods: RNA-sequencing and western blotting were used to compare gene and protein expression between untreated and TGF-β2-treated equine bone marrow-derived MSCs (BM-MSCs).