Formulation development and comparability studies with an aluminum-salt adjuvanted SARS-CoV-2 spike ferritin nanoparticle vaccine antigen produced from two different cell lines.

The development of safe and effective second-generation COVID-19 vaccines to improve affordability and storage stability requirements remains a high priority to expand global coverage. In this report, we describe formulation development and comparability studies with a self-assembled SARS-CoV-2 spike ferritin nanoparticle vaccine antigen (called DCFHP), when produced in two different cell lines and formulated with an aluminum-salt adjuvant (Alhydrogel, AH). Varying levels of phosphate buffer altered the extent and strength of antigen-adjuvant interactions, and these formulations were evaluated for their (1) in vivo performance in mice and (2) in vitro stability profiles.

A ferritin-based COVID-19 nanoparticle vaccine that elicits robust, durable, broad-spectrum neutralizing antisera in non-human primates.

While the rapid development of COVID-19 vaccines has been a scientific triumph, the need remains for a globally available vaccine that provides longer-lasting immunity against present and future SARS-CoV-2 variants of concern (VOCs). Here, we describe DCFHP, a ferritin-based, protein-nanoparticle vaccine candidate that, when formulated with aluminum hydroxide as the sole adjuvant (DCFHP-alum), elicits potent and durable neutralizing antisera in non-human primates against known VOCs, including Omicron BQ.1, as well as against SARS-CoV-1.

Formulation development and comparability studies with an aluminum-salt adjuvanted SARS-CoV-2 Spike ferritin nanoparticle vaccine antigen produced from two different cell lines.

The development of safe and effective second-generation COVID-19 vaccines to improve affordability and storage stability requirements remains a high priority to expand global coverage. In this report, we describe formulation development and comparability studies with a self-assembled SARS-CoV-2 spike ferritin nanoparticle vaccine antigen (called DCFHP), when produced in two different cell lines and formulated with an aluminum-salt adjuvant (Alhydrogel, AH). Varying levels of phosphate buffer altered the extent and strength of antigen-adjuvant interactions, and these formulations were evaluated for their (1) performance in mice and (2) stability profiles.

HIV-1 prehairpin intermediate inhibitors show efficacy independent of neutralization tier.

HIV-1 strains are categorized into one of three neutralization tiers based on the relative ease by which they are neutralized by plasma from HIV-1-infected donors not on antiretroviral therapy; tier-1 strains are particularly sensitive to neutralization while tier-2 and tier-3 strains are increasingly difficult to neutralize. Most broadly neutralizing antibodies (bnAbs) previously described target the native prefusion conformation of HIV-1 Envelope (Env), but the relevance of the tiered categories for inhibitors targeting another Env conformation, the prehairpin intermediate, is not well understood. Here, we show that two inhibitors targeting distinct highly conserved regions of the prehairpin intermediate have strikingly consistent neutralization potencies (within ~100-fold for a given inhibitor) against strains in all three neutralization tiers of HIV-1; in contrast, best-in-class bnAbs targeting diverse Env epitopes vary by more than 10,000-fold in potency against these strains.

A ferritin-based COVID-19 nanoparticle vaccine that elicits robust, durable, broad-spectrum neutralizing antisera in non-human primates.

While the rapid development of COVID-19 vaccines has been a scientific triumph, the need remains for a globally available vaccine that provides longer-lasting immunity against present and future SARS-CoV-2 variants of concern (VOCs). Here, we describe DCFHP, a ferritin-based, protein-nanoparticle vaccine candidate that, when formulated with aluminum hydroxide as the sole adjuvant (DCFHP-alum), elicits potent and durable neutralizing antisera in non-human primates against known VOCs, including Omicron BQ.1, as well as against SARS-CoV-1.

Adaption of a conventional ELISA to a 96-well ELISA-Array for measuring the antibody responses to influenza virus proteins and vaccines.

We describe an adaptation of conventional ELISA methods to an ELISA-Array format using non-contact Piezo printing of up to 30 spots of purified recombinant viral fusion proteins and vaccine on 96 well high-protein binding plates. Antigens were printed in 1 nanoliter volumes of protein stabilizing buffer using as little as 0.25 nanograms of protein, 2000-fold less than conventional ELISA.

Light regulation of light-harvesting antenna size substantially enhances photosynthetic efficiency and biomass yield in green algae.

One of the major factors limiting biomass productivity in algae is the low thermodynamic efficiency of photosynthesis. The greatest thermodynamic inefficiencies in photosynthesis occur during the conversion of light into chemical energy. At full sunlight the light-harvesting antenna captures photons at a rate nearly 10 times faster than the rate-limiting step in photosynthetic electron transport.

Fine-tuning the photosynthetic light harvesting apparatus for improved photosynthetic efficiency and biomass yield.

Photosynthetic electron transport rates in higher plants and green algae are light-saturated at approximately one quarter of full sunlight intensity. This is due to the large optical cross section of plant light harvesting antenna complexes which capture photons at a rate nearly 10-fold faster than the rate-limiting step in electron transport. As a result, 75% of the light captured at full sunlight intensities is reradiated as heat or fluorescence.

Functional Enrichment and Analysis of Antigen-Specific Memory B Cell Antibody Repertoires in PBMCs.

Phenotypic screening of antigen-specific antibodies in human blood is a common diagnostic test for infectious agents and a correlate of protection after vaccination. In addition to long-lived antibody secreting plasma cells residing in the bone marrow, memory B cells are a latent source of antigen-experienced, long-term immunity that can be found at low frequencies in circulating peripheral blood mononuclear cells (PBMCs). Assessing the genotype, clonal frequency, quality, and function of antibodies resulting from an individual's persistent memory B cell repertoire can help inform the success or failure of immune protection.

Experimental mapping of soluble protein domains using a hierarchical approach.

Exploring the function and 3D space of large multidomain protein targets often requires sophisticated experimentation to obtain the targets in a form suitable for structure determination. Screening methods capable of selecting well-expressed, soluble fragments from DNA libraries exist, but require the use of automation to maximize chances of picking a few good candidates. Here, we describe the use of an insertion dihydrofolate reductase (DHFR) vector to select in-frame fragments and a split-GFP assay technology to filter-out constructs that express insoluble protein fragments.

The cost of richness: the effect of the size and diversity of decision sets on post-decision regret.

Decision making is often made difficult by the knowledge that one has to live with the outcomes of one's choices and with the regret that these might engender. Formal theories propose that regret is proportional to the difference between the outcome of the option chosen and the expected outcome of the next best alternative that one may have chosen instead. It follows that the number of alternatives available for choice does not affect post-decisional regret.

Domain orientation in the inactive response regulator Mycobacterium tuberculosis MtrA provides a barrier to activation.

The structure of MtrA, an essential gene product for the human pathogen Mycobacterium tuberculosis, has been solved to a resolution of 2.1 A. MtrA is a member of the OmpR/PhoB family of response regulators and represents the fourth family member for which a structure of the protein in its inactive state has been determined.

Structure of a cholesterol-binding protein deficient in Niemann-Pick type C2 disease.

Niemann-Pick disease type C2 (NP-C2) is a fatal hereditary disease characterized by accumulation of low-density lipoprotein-derived cholesterol in lysosomes. Here we report the 1.7-A resolution crystal structure of the cholesterol-binding protein deficient in this disease, NPC2, and the characterization of its ligand binding properties.

The effect of stress on the suppression of erroneous competing responses.

Abstract Evidence exists that the intention to perform certain cognitive tasks activates, unintentionally, competing responses and computations that intrude on the performance of the intended tasks. For the intended task to be performed effectively, such intrusions must be controlled. Two experiments were carried out to test the hypothesis that stress heightens the difficulty of exercising effective control over erroneous competing responses, a possible explanation of decrements in the performance of cognitive tasks under stress.

The effect of psychological stress and tolerance of ambiguity on stereotypic attributions.

Abstract Recent research on the relationship between cognition and affect suggests the prediction that psychological stress encourages stereotyping. Yet the empirical evidence regarding this proposition is inconclusive. This study examined the effect of stress on the perception of illusory correlations, which comprise a particular manifestation of stereotypic attributions, and the moderating role of tolerance of ambiguity.

Changes of brain anatomy in patients with posttraumatic stress disorder: a pilot magnetic resonance imaging study.

No abnormalities in magnetic resonance images were recorded in patients with posttraumatic stress disorder other than an increased incidence (50%) of a small cleft in the callosal-septal interface, a cavum of the septum pellucidum. A similar grade of cavum was obtained in 14% of normal volunteers matched for age, socioeconomic background, and military experience. The cavum is believed to have antedated the disorder and is conceived to be a neurodevelopmental aberration.

Controlling the uncontrollable: effects of stress on illusory perceptions of controllability.

Individuals' failure to exercise actual control over an event might be compensated for by trying to bolster a generalized, subjective sense of control. Control might then be sought by undertaking acts the effect of which on the environment is illusory. This observation led to the hypothesis that stress, which undermines persons' sense of control, would engender illusory perceptions of controllability.

Automatic ventricular cavity boundary detection from sequential ultrasound images using simulated annealing.

An automatic algorithm has been developed for high-speed detection of cavity boundaries in sequential 2-D echocardiograms using an optimization algorithm called simulated annealing (SA). The algorithm has three stages. (1) A predetermined window of size nxm is decimated to size n'xm' after low-pass filtering.

Stressors and tasks: how and when should stressors be introduced during training for task performance in stressful situations?

Studies on the training of individuals for task performance in stressful situations have typically evaluated procedures that simultaneously expose trainees to tasks and to stressors. Such procedures might create a mutual interference of the stressor with task acquisition, or conversely, of preoccupation with task acquisition with familiarization with the stressors. Using a sample of 180 males, the present study compared a procedure that temporally separates task acquisition from exposure to stressors ("phased training") with the more typical approach which combines the two ("combined training").

Dilemmas concerning the training of individuals for task performance under stress.

The relative effectiveness of five procedures for the training of individuals to perform tasks under stress was tested in a criterion situation, where subjects were requested to perform a visual search task under the threat of electric shocks. During training on the task, different groups of subjects received shocks of criterion-level intensity; milder than criterion-level intensity; gradually increasing intensity; randomly varying intensity. The last group received no shocks at all.

Patterns of fidelity between training and criterion situations as determinants of performance in stressful situations.

The training of individuals for task performance under stress poses a dilemma concerning the degree to which stressor characteristics of the criterion situation should be represented with a high degree of fidelity during training. High fidelity training is likely to reduce the novelty of the criterion situation and familiarize the trainee with his emotional and physiological reactions to stress. On the other hand, the exposure of the trainee to high stress levels during training might interfere with task acquisition and intensify his fears and emotional sensitivity.