Immune correlates of protection by mRNA-1273 vaccine against SARS-CoV-2 in nonhuman primates.

Immune correlates of protection can be used as surrogate endpoints for vaccine efficacy. Here, nonhuman primates (NHPs) received either no vaccine or doses ranging from 0.3 to 100 µg of the mRNA-1273 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine. mRNA-1273 vaccination elicited circulating and mucosal antibody responses in a dose-dependent manner. Viral replication was significantly reduced in bronchoalveolar lavages and nasal swabs after SARS-CoV-2 challenge in vaccinated animals and most strongly correlated with levels of anti­S antibody and neutralizing activity. Lower antibody levels were needed for reduction of viral replication in the lower airway than in the upper airway. Passive transfer of mRNA-1273­induced immunoglobulin G to naïve hamsters was sufficient to mediate protection. Thus, mRNA-1273 vaccine­induced humoral immune responses are a mechanistic correlate of protection against SARS-CoV-2 in NHPs.

Immune Correlates of Protection by mRNA-1273 Immunization against SARS-CoV-2 Infection in Nonhuman Primates.

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 SUMMARY: mRNA-1273 vaccine-induced antibody responses are a mechanistic correlate of protection against SARS-CoV-2 infection in NHP.

The BE-ACTIV Project: How Research, Professional Training, Education, and Practice Were Integrated in a Single Clinical Trial.

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.

Late-life bereavement and complicated grief: a proposed comprehensive framework.

OBJECTIVES: The construct of complicated grief (CG) has garnered increased empirical attention since it has been proposed as a diagnostic category for the upcoming Diagnostic and Statistical Manual of Mental Disorders-V. The aim of this article is to critically examine construct validity in light of a proposed conceptual framework, with special emphasis on understanding late-life bereavement. METHOD: This is a review article that critically examined current bereavement and grief models. We explored discriminant and convergent validity between CG and uncomplicated grief (UG) and other psychopathological constructs in terms of symptom intensity, symptom trajectories, bereavement outcomes, and treatment response. RESULTS: The findings from this review show mixed support for differentiating CG from other outcomes of bereavement for the following reasons: (1) a clear boundary between CG and UG has not been adequately supported, (2) symptoms of CG and bereavement-related depression and anxiety overlap, although there is some evidence of incremental validity in that CG symptoms predict global functioning above and beyond symptoms of depression, and (3) the treatment literature demonstrated that general grief interventions and treatment targeted for improving depression are ineffective at treating symptoms of CG, whereas interventions specially tailored to treating CG have been moderately effective. The findings also emphasize the importance of considering pre-bereavement circumstances, such as preexisting depression, in the conceptualization of broader bereavement outcome. CONCLUSION: There were mixed findings supporting the construct validation of CG. A comprehensive framework that emphasizes pre-bereavement circumstances was proposed in order to better predict various grief trajectories and outcomes of late-life loss.

The Pleasant Events Schedule - nursing home version: a useful tool for behavioral interventions in long-term care.

OBJECTIVES: Behavioral interventions for depression emphasize increasing engagement in pleasant events, requiring reliable and valid assessment of events. Versions of the Pleasant Events Schedule (PES) have been developed for this purpose. Although depression is prevalent in nursing homes, no PES version is yet available specifically for this setting, where access to pleasant events is circumscribed. Our goal was to develop and evaluate a nursing home version of the PES. METHOD: We developed the PES-NH on two samples of nursing home residents. We first sampled activity frequency and pleasantness for 10 residents of a large, urban facility. Using these pilot data and PES-Alzheimer's Disease items, we interviewed 37 more residents from the same facility, yielding a comprehensive list of events that residents find pleasant. From the second sample of 48 residents, we present normative and psychometric data on the new scale. RESULTS: A 30-item inventory was able to cover the content of daily activities available in nursing homes. Scales derived from these items were internally consistent and reliable over time. Frequency of event participation was related to perceptions of quality of life, depression and positive affect independent of the overall tendency to rate events as pleasantness. Event participation was unrelated to negative affect, suggesting that activity engagement is linked to depression through its impact on positive affect. CONCLUSION: Data from this study provide base rate information for planning pleasant event interventions in nursing homes. The PES-NH is a useful and valid tool for implementing behavioral interventions for depression in these settings.