Beta-spike-containing boosters induce robust and functional antibody responses to SARS-CoV-2 in macaques primed with distinct vaccines.

The reduced effectiveness of COVID-19 vaccines due to the emergence of variants of concern (VOCs) necessitated the use of vaccine boosters to bolster protection against disease. However, it remains unclear how boosting expands protective breadth when primary vaccine platforms are distinct and how boosters containing VOC spike(s) broaden humoral responses. Here, we report that boosters composed of recombinant spike antigens of ancestral (prototype) and Beta VOCs elicit a robust, pan-VOC, and multi-functional humoral response in non-human primates largely independent of the primary vaccine series platform. Interestingly, Beta-spike-containing boosters stimulate immunoglobulin A (IgA) with a greater breadth of recognition in protein-primed recipients when administered with adjuvant system 03 (AS03). Our results highlight the utility of a component-based booster strategy for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) for broad humoral recognition, independent of primary vaccine series. This is of high global health importance given the heterogeneity of primary vaccination platforms distributed.

Antibodies against the Ebola virus soluble glycoprotein are associated with long-term vaccine-mediated protection of non-human primates.

The 2013 Ebola epidemic in Central and West Africa heralded the emergence of wide-spread, highly pathogenic viruses. The successful recombinant vector vaccine against Ebola (rVSVΔG-ZEBOV-GP) will limit future outbreaks, but identifying mechanisms of protection is essential to protect the most vulnerable. Vaccine-induced antibodies are key determinants of vaccine efficacy, yet the mechanism by which vaccine-induced antibodies prevent Ebola infection remains elusive. Here, we exploit a break in long-term vaccine efficacy in non-human primates to identify predictors of protection. Using unbiased humoral profiling that captures neutralization and Fc-mediated functions, we find that antibodies specific for soluble glycoprotein (sGP) drive neutrophil-mediated phagocytosis and predict vaccine-mediated protection. Similarly, we show that protective sGP-specific monoclonal antibodies have elevated neutrophil-mediated phagocytic activity compared with non-protective antibodies, highlighting the importance of sGP in vaccine protection and monoclonal antibody therapeutics against Ebola virus.

Nucleocapsid-specific antibody function is associated with therapeutic benefits from COVID-19 convalescent plasma therapy.

Coronavirus disease 2019 (COVID-19) convalescent plasma (CCP), a passive polyclonal antibody therapeutic agent, has had mixed clinical results. Although antibody neutralization is the predominant approach to benchmarking CCP efficacy, CCP may also influence the evolution of the endogenous antibody response. Using systems serology to comprehensively profile severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) functional antibodies of hospitalized people with COVID-19 enrolled in a randomized controlled trial of CCP (ClinicalTrials.gov: NCT04397757), we find that the clinical benefits of CCP are associated with a shift toward reduced inflammatory Spike (S) responses and enhanced nucleocapsid (N) humoral responses. We find that CCP has the greatest clinical benefit in participants with low pre-existing anti-SARS-CoV-2 antibody function and that CCP-induced immunomodulatory Fc glycan profiles and N immunodominant profiles persist for at least 2 months. We highlight a potential mechanism of action of CCP associated with durable immunomodulation, outline optimal patient characteristics for CCP treatment, and provide guidance for development of a different class of COVID-19 hyperinflammation-targeting antibody therapeutic agents.

Advanced practice providers proficiency-based model of ultrasound training and practice in the ED.

Competency in the application of point-of-care ultrasound (POCUS) has come to be an expected fundamental skill set for advanced practice providers (APPs) in the emergency department. Both American College of Emergency Physicians and the Society of Emergency Medicine Physician Assistants approve of and endorse POCUS use by APPs. However, clinical exposure to and practice of ultrasound in this setting is often variable and without structure. POCUS training must be evolved into a system where developed skills are compatible with clinical need and expectations of APPs. At our institution, we developed a formal, structured POCUS training program for emergency medicine (EM) APPs (including physician assistants and nurse practitioners) and evaluated its efficacy quantitatively by means of a proficiency index. This report examines the EM POCUS training most common to physician assistants and nurse practitioners before practicing at our institution and explores the components of our POCUS training program that have affected program development.