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Immune correlates of protection can be used as surrogate endpoints for vaccine efficacy. The nonhuman primate (NHP) model of SARS-CoV-2 infection replicates key features of human infection and may be used to define immune correlates of protection following vaccination. Here, NHP received either no vaccine or doses ranging from 0.3 - 100 μg of mRNA-1273, a mRNA vaccine encoding the prefusion-stabilized SARS-CoV-2 spike (S-2P) protein encapsulated in a lipid nanoparticle. mRNA-1273 vaccination elicited robust circulating and mucosal antibody responses in a dose-dependent manner. Viral replication was significantly reduced in bronchoalveolar lavages and nasal swabs following SARS-CoV-2 challenge in vaccinated animals and was most strongly correlated with levels of anti-S antibody binding and neutralizing activity. Consistent with antibodies being a correlate of protection, passive transfer of vaccine-induced IgG to naïve hamsters was sufficient to mediate protection. Taken together, these data show that mRNA-1273 vaccine-induced humoral immune responses are a mechanistic correlate of protection against SARS-CoV-2 infection in NHP.mRNA-1273 vaccine-induced antibody responses are a mechanistic correlate of protection against SARS-CoV-2 infection in NHP.

Background: Acute Myeloid Leukemia (AML) is associated with mutational diversity. Previous studies have shown that obesity has strong links to genomic instability directly through metabolic parameters, or indirectly through inflammation-mediated pathways, and is thereby strongly associated with cancer initiation. Interestingly, obese patients have been reported to develop fewer mutations and have less dependence on "driver genes" like KRAS in favor of cell signaling alterations in colon cancer. Past work has also shown that transgenic mice have lower cholesterol levels and metabolism resembling the Warburg effect in the liver. We sought to find an association between RAS mutations and obesity in AML with aims to (1) find evidence of a "protective effect" of obesity against the acquisition of RAS (KRAS and NRAS) and (2) detect differential mutational expression among RAS-negative and RAS-positive AML to uncover possible tumor vulnerability. Methods: After IRB approval, 186 AML patients were screened from Baylor College of Medicine Institutions [Michael E. DeBakey VA Medical Center, and Baylor St. Luke's Medical Center]. 32 patients with next-generation sequencing (NGS) for myeloid mutations, complete blood count (CBC), body mass index (BMI), age, diabetes mellitus (DM), smoking, and lipid data were selected. Differential BMI was estimated by t-test in those with or without RAS mutations. A similar analysis was performed among patients with or without RAS mutations for relevant variables. The logistic regression model was used to independently assess the effect of BMI on RAS acquisition. All statistical analysis was performed using SAS software. Results: In our cohort, 22/32 [68.7%] and 10/32 [31.3%] patients had RAS-negative and RAS-positive AMLs, respectively. Differential expression for CBC and lipid profile [i.e. total, LDL, HDL-cholesterol, and triglycerides) in RAS-negative and RAS-positive AMLs are depicted in Table 1. BMI was higher for patients without RAS mutations than for patients with RAS mutations [30.7 vs. 25.8, p=0.0029]. No significant associations between DM and smoking were found with RAS-negative or RAS-positive AMLs. RAS-negative and RAS-positive patients were found to have similar levels of LDL, HDL, and TRG. A trend between RAS-negative and RAS-positive in terms of TC levels [173 vs. 191, p=0.12] was demonstrated. BMI was independently associated with differential leukemia RAS acquisition, p=0.04 [stepwise selection p Conclusions: BMI alone remains as a predictor of "protective effect" against RAS mutations. Consistent with previous studies in colon cancer, rather than depending on mutations in "driver genes" like RAS, these patients develop mutations in alternative signaling pathways (particularly FLT3 as noted), as obesity-related inflammation and cytokine release may already be activating RAS-dependent pathways. While a larger number of patients are needed to validate our findings, we provide evidence that excess body weight has protective effects against acquiring RAS mutations. Additionally, it would be interesting to investigate "permissive" differential bone marrow microenvironment factors (i.e. cytokines/chemokines) that operate in high vs. low BMI settings that either facilitate or decrease mutation acquisition and/or RAS clonal expansion. Disclosures Rivero: celgene: Membership on an entity's Board of Directors or advisory committees; Incyte: Membership on an entity's Board of Directors or advisory committees; agios: Membership on an entity's Board of Directors or advisory committees.

Immune correlates of protection can be used as surrogate endpoints for vaccine efficacy. The nonhuman primate (NHP) model of SARS-CoV-2 infection replicates key features of human infection and may be used to define immune correlates of protection following vaccination. Here, NHP received either no vaccine or doses ranging from 0.3 – 100 μg of mRNA-1273, a mRNA vaccine encoding the prefusion-stabilized SARS-CoV-2 spike (S-2P) protein encapsulated in a lipid nanoparticle. mRNA-1273 vaccination elicited robust circulating and mucosal antibody responses in a dose-dependent manner. Viral replication was significantly reduced in bronchoalveolar lavages and nasal swabs following SARS-CoV-2 challenge in vaccinated animals and was most strongly correlated with levels of anti-S antibody binding and neutralizing activity. Consistent with antibodies being a correlate of protection, passive transfer of vaccine-induced IgG to naïve hamsters was sufficient to mediate protection. Taken together, these data show that mRNA-1273 vaccine-induced humoral immune responses are a mechanistic correlate of protection against SARS-CoV-2 infection in NHP.One-Sentence SummarymRNA-1273 vaccine-induced antibody responses are a mechanistic correlate of protection against SARS-CoV-2 infection in NHP.

This article describes how research, practice, and education were integrated in a National Institutes of Mental Health-funded clinical trial for treating depression in nursing homes. Involving undergraduate and doctoral students in this clinical trial supported the development of key competencies, expanded the professional pipeline, and provided an avenue for disseminating the treatment to other settings. The clinical trial served as a teaching laboratory for sixteen undergraduate and six doctoral students to (1) observe the culture of older adults in nursing homes, (2) develop and adapt clinical skills to a challenging patient population, (3) refine skills for collaborating in multidisciplinary teams, and (4) appreciate the relationship between science and practice. Dissemination of the intervention to nonresearch settings was served when the students took their skills to the settings where they launched their careers. Involvement of trainees in clinical trial research expands and enriches the capacity of the health care workforce in evidence-based practice and practice-informed research.

Introduction The object of this study was to provide an updated evaluation of the quality of antidepressant management and prescribing patterns in nursing homes in the context of organizational and resident factors. Design Pearson correlation and chi-square analyses were conducted using information gathered from random nursing home charts. Setting Nursing home facilities in and around the Louisville, KY, metropolitan area (n = 10). Participants Chart reviews were randomly chosen for 20% of long term care resident records in participating homes (n = 209). Measurements Demographic information, documentation of depression diagnoses, and antidepressant prescribing patterns were evaluated using the Quality of Depression Management and Antidepressant Prescribing rating scale and information found in the Minimum Data Set 2.0. Results Of the sample, 59.8% was prescribed antidepressants at the time of the chart review; 205 chart reviews indicated the absence or presence of a depression diagnosis. For those with documented depression diagnoses (n = 126), nearly one-quarter were not prescribed antidepressants. Of 79 chart reviews indicating no depression diagnosis, nearly a third were receiving an antidepressant. Documentation related to changes in dosing, the presence or absence of side effects, or reasons for continuation were suboptimal. Conclusion Discrepancy between antidepressant prescribing and the presence/absence of depression diagnoses continue to exist for nursing home residents. The quality of antidepressant documentation in nursing home charts continues to be inadequate. Future research should aim to explore possible solutions to these discrepancies and deficiencies in documentation.