Vaccine efficacy can be increased by arraying immunogens in multivalent form on virus-like nanoparticles to enhance B cell activation. However, the effects of antigen copy number, spacing, and affinity, as well as the dimensionality and rigidity of scaffold presentation on B cell activation remain poorly understood. Here, we displayed the clinical vaccine immunogen eOD-GT8, an engineered outer domain of the HIV-1 glycoprotein-120, on DNA origami nanoparticles to systematically interrogate the impact of these nanoscale parameters on B cell activation in vitro. We found that B cell signalling is maximized by as few as five antigens maximally spaced on the surface of a 40 nm viral-like nanoparticle. Increasing antigen spacing up to ~25–30 nm monotonically increases B cell receptor activation. Moreover, scaffold rigidity is essential for robust B cell triggering. These results reveal molecular vaccine design principles that may be used to drive functional B cell responses.

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The IQ Consortium reports on the current state of process analytical technology (PAT) for active pharmaceutical ingredient (API) development in branded pharmaceutical companies. The article uses an API process workflow (process steps from raw material identification through to finished API) to provide representative examples, including why and how the pharmaceutical industry uses PAT tools in API development. The use of PAT can improve R&D efficiency and minimize personnel hazards associated with sampling hazardous materials for in-process testing. Although not all steps or chemical processes are readily amenable to the use of the PAT toolbox, when appropriate, PAT enables reliable and rapid (real or near time) analyses of processes that may contain materials that are highly hazardous, transient, or heterogeneous. These measurements can provide significant data for developing process chemistry understanding, and they may include the detection of previously unknown reaction intermediates, mechanisms, or relationships between process variables. As the process becomes defined and understanding is gained through these measurements, the number of parameters suspected to be critical is reduced. As the process approaches the commercial manufacturing stage and the process design space is established, a simplification of the monitoring and control technology, as much as is practical, is desired. In many cases, this results in controls being either off-line, or if in situ control is required, the results from PAT are correlated with simple manufacturing measurements such as temperature and pressure.

The Src and Syk families of kinases are two distinct sets of kinases that play critical roles in initiating membrane-proximal B cell receptor (BCR) signaling. However, unlike in other lymphocytes, such as T cells, the “division of labor” between Src family kinases (SFKs) and Syk in B cells is not well separated, because both Syk and SFKs can phosphorylate immunoreceptor tyrosine-based activation motifs (ITAMs) present in proteins comprising the B cell receptor (BCR). To understand why B cells require both SFKs and Syk for activation, we investigated the roles of both families of kinases in BCR signaling with computational modeling and in vitro experiments. Our computational model suggested that positive feedback enabled Syk to substantially compensate for the absence of SFKs when spatial clustering of BCRs was induced by multimeric ligands. We confirmed this prediction experimentally. In contrast, when B cells were stimulated by monomeric ligands that failed to produce BCR clustering, both Syk and SFKs were required for complete and rapid BCR activation. Our data suggest that SFKs could play a pivotal role in increasing BCR sensitivity to monomeric antigens of pathogens and in mediating a rapid response to soluble multimeric antigens of pathogens that can induce spatial BCR clustering.

We have investigated the structural and magnetic properties of polycrystalline Cu‐substituted cobalt ferrite (CuxCo1−xFe2O4: x = 0.00, 0.15, 0.30, 0.45, 0.60) nanoparticles, synthesized via chemical coprecipitation method. The prepared samples were of single phase as confirmed by X‐ray diffraction analysis. The mean crystallite size ranged from 44 to 65 nm was obtained using Scherrer's formula. M‐T curves revealed that the Curie temperature of all the samples was above room temperature and it was found to decrease with increasing Cu concentration, which was supported by Mössbauer spectra. Field cooled (FC) hysteresis curves showed ferrimagnetic nature at 5 K and room temperature. It was observed that careful variation of Cu concentration in cobalt ferrite lead to weak A‐B interaction with tunable magnetic properties.

Sm3+ doped spinel cobalt ferrite nanoparticles with a generic formula CoSmxFe2−xO4 (x = 0.00, 0.06, 0.12 and 0.18) were prepared using wet chemical co-precipitation technique. The structural, optical, magnetic and dielectric characteristics of the samples were investigated carefully. The phase purity and growth of spinel cubic structure was verified by room temperature x-ray diffractograms. Mean crystallite size was observed within the range of 6 nm to 15 nm as calculated from Scherrer’s formula. A blue shift in the indirect optical band gap was noticed with increasing Sm percentage as observed in UV–vis spectra due to the nanosize effect. Superparamagnetic nature at 300 K was detected for all Sm doped ferrite samples. Field cooled (150 kOe) M-H loops obtained at 5 K revealed a large amount of exchange bias field (≈4 kOe) together with high coercivity for the sample having smallest sized particles. Dielectric responses of all samples showed that the hopping of electrons was the fundamental charge conduction mechanism and grain boundaries play a crucial role in determining the dielectric properties.

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