A Next-Generation Adenoviral Vaccine Elicits Mucosal and Systemic Immunogenicity and Reduces Viral Shedding after SARS-CoV-2 Challenge in Nonhuman Primates.

As new SARS-CoV-2 variants continue to emerge and impact communities worldwide, next-generation vaccines that enhance protective mucosal immunity may have a significant impact on productive infection and transmission. We have developed recombinant non-replicating adenovirus serotype 5 (rAd5) vaccines delivered by mucosal administration that express both target antigen and a novel molecular adjuvant within the same cell. Here, we describe the immunogenicity of three unique SARS-CoV-2 rAd5 vaccine candidates and their efficacy following viral challenge in non-human primates (NHPs). Intranasal immunization with rAd5 vaccines expressing Wuhan, or Beta variant spike alone, or Wuhan spike and nucleocapsid elicited strong antigen-specific serum IgG and IgA with neutralizing activity against multiple variants of concern (VOC). Robust cross-reactive mucosal IgA was detected after a single administration of rAd5, which showed strong neutralizing activity against multiple VOC. Additionally, mucosal rAd5 vaccination increased spike-specific IFN-γ producing circulating T-cells. Upon Beta variant SARS-CoV-2 challenge, all the vaccinated NHPs exhibited significant reductions in viral load and infectious particle shedding in both the nasal passages and lower airways. These findings demonstrate that mucosal rAd5 immunization is highly immunogenic, confers protective cross-reactive antibody responses in the circulation and mucosa, and reduces viral load and shedding after SARS-CoV-2 challenge.

Bispectral EEG (BSEEG) to assess arousal after electro-convulsive therapy (ECT).

OBJECTIVES: Postictal confusion is encountered among most patients following electro-convulsive therapy (ECT). This study aimed to test the capabilities of a point-of-care electroencephalography (EEG) method to quantitatively measure and monitor postictal confusion immediately following ECT. We evaluated whether a two-channel frontal EEG device may provide a purely quantitative measure of the postictal state that could aid in the continuous, clinical monitoring of patients following ECT. METHODS: 50 patients receiving ECT at the University of Iowa Hospitals and Clinics were recruited for this study. Subsequently, we obtained 5 min of frontal bispectral EEG (BSEEG) recording from a hand-held EEG device at baseline and 10-20 min following ECT. We performed power spectral density analysis to yield a "BSEEG" score and to capture the difference between patients at baseline and after ECT. RESULTS: The BSEEG score was demonstrated to be a significant indicator of postictal confusion compared to baseline. For 5 patients, we also obtained continuous EEG recordings following ECT to determine the time course required for a patient's BSEEG score to return to baseline. In this subset of patients, it took between 2 and 3 h in duration for the BSEEG score to return to the baseline range. CONCLUSIONS: In this pilot study, we showed that BSEEG score was able to distinguish between baseline condition and postictal confusion in patients treated with ECT, and assess the duration for recovery from postictal confusion following ECT. BSEEG may provide a more sensitive measure of arousal in patients following ECT compared to traditional survey-based methods.