Biology subjects

Jaramillo, S. A.

Publications and source records attributed to Jaramillo, S. A..

3 recordsLinked to original sources

bioRxiv2021

Dual roles of a novel oncolytic viral vector-based SARS-CoV-2 vaccine: preventing COVID-19 and treating tumor progression

The ongoing coronavirus disease 2019 (COVID-19) pandemic is caused by infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Cancer patients are usually immunocompromised and thus are particularly susceptible to SARS-CoV-2 infection resulting in COVID-19. Although many vaccines against COVID-19 are being preclinically or clinically tested or approved, none have yet been specifically developed for cancer patients or reported as having potential dual functions to prevent COVID-19 and treat cancer. Here, we confirmed that COVID-19 patients with cancer have low levels of antibodies against the spike (S) protein, a viral surface protein mediating the entry of SARS-CoV-2 into host cells, compared with COVID-19 patients without cancer. We developed an oncolytic herpes simplex virus-1 vector-based vaccine named oncolytic virus (OV)-spike. OV-spike induced abundant anti-S protein neutralization antibodies in both tumor-free and tumor-bearing mice, which inhibit infection of VSV-SARS-CoV-2 and wild-type (WT) live SARS-CoV-2 as well as the B.1.1.7 variant in vitro. In the tumor-bearing mice, OV-spike also inhibited tumor growth, leading to better survival in multiple preclinical tumor models than the untreated control. Furthermore, OV-spike induced anti-tumor immune response and SARS-CoV-2-specific T cell response without causing serious adverse events. Thus, OV-spike is a promising vaccine candidate for both preventing COVID-19 and enhancing the anti-tumor response. One Sentence SummaryA herpes oncolytic viral vector-based vaccine is a promising vaccine with dual roles in preventing COVID-19 and treating tumor progression

microbiology↗

bioRxiv2021

The Effect of Minnelide against SARS-CoV-2 in a Murine Model

Severe acute respiratory syndrome coronavirus 2, SARS-CoV-2, is the causative agent of coronavirus disease 2019, COVID-19, and the current COVID-19 pandemic. Even as more vaccine candidates are released, more treatment options are critically needed. Here, we investigated the use of Minnelide, a water soluble pro-drug with anti-inflammatory properties, for the treatment of COVID-19. To do this, k18-hACE2 mice were infected with SARS-CoV-2 or given PBS control intranasally. The next day mice were either treated daily with low dose (0.0025mg/day) or high dose Minnelide (0.005mg/day), or given vehicle control intraperitoneal. Mice were weighed daily, and sacrificed at day 6 and 10 post-infection to analyze viral burden, cytokine response, and pathology. We observed a reduction in viral load in the lungs of Minnelide-treated mice infected with SARS-CoV-2 at day 10 post-infection compared to day 6 post-infection. All SARS-CoV-2 infected non-treated mice were moribund six days post-infection while treatment with Minnelide extended survival for both low (60% survival) and high (100% survival) dose treated mice ten days post-infection. Interestingly, cytokine analysis demonstrated a significant reduction in IL-6 (lung and heart) and D-dimer (serum) in high dose treated SARS-CoV-2 infected mice compared to mice infected with SARS-CoV-2 alone at day 6 post-infection. Additionally, histology analysis revealed that Minnelide treatment significantly improved lung pathology ten days post-infection with SARS-CoV-2 with all the mice exhibiting normal lung tissue with thin alveolar septa and no inflammatory cells. Overall, our study exhibits potential for the use of Minnelide to improve survival in COVID-19 patients.

microbiology↗

bioRxiv2020

Soluble corn fiber reduces ovalbumin-induced sinonasal inflammation via the gut microbiota-airway axis

Asthma is a chronic airway inflammatory disease that affects approximately 300 million people worldwide, causing a substantial healthcare burden. Although there is a large degree of heterogeneity in the inflammatory response of asthmatics, a subset of patients are characterized by type-2 inflammation, which is in part mediated by TH2 cells in both the upper and lower airways. Asthma prevalence is increased in low-socioeconomic-status populations, where disparities in health behavior exist, including a shift toward a western diet characterized by low dietary fiber. Gut microbes metabolize fiber into short chain fatty acids that can reduce type-2 inflammation in peripheral organs, such as the airways. We hypothesized that soluble fiber can reduce ovalbumin (OVA)-induced upper airway inflammation in the context of the unified airway hypothesis, in mice maintained on ingredient-matched western (WD) and control diets (CD) through production of short chain fatty acids. Our results show that soluble fiber reduces IL-4 and IL-13 gene expression (p<0.05, Mann Whitney) in the sinonasal cavity of CD-fed mice, but this effect was lost in WD-fed mice. This loss of protection in WD-fed mice parallels compositional changes of the cecal and fecal microbiota. Mice fed a soluble fiber supplement while being maintained on a WD had altered microbial communities characterized by lower abundance of fiber fermentering bacteria. This work can be used to develop effective microbiome-based therapeutics as a low-cost method to reduce asthma morbidity. IMPORTANCEPrevious research has supported that western-style diets, typically high-fat and low-fiber, are associated with changes in the gut microbiome and increased inflammation. Western diets are accessible and prominent in low-socioeconomic-status populations, where asthma rates are highest; however, there has yet to be a low-cost asthma therapeutic. For the first time, we investigated whether supplementation with a physiologically relevant quantity of soluble corn fiber can reduce allergic airway inflammation. Our study supports that soluble corn fiber supplementation is associated with compositional shifts of the gut microbiota and reduced airway inflammation, promoting the use of fiber as a low-cost microbiome modifying therapy to reduce asthma-associated inflammation. However, soluble corn fiber in conjunction with a western diet resulted in an alternate gut microbiome composition and loss of protection against allergic airway inflammation. These findings further support the importance of the gut microbiota in host health.

microbiology↗