Rapid Deployment of Multiple Tactics to Address Severe Acute Respiratory Syndrome Coronavirus 2 Vaccine Uptake in Healthcare Employees With a Focus on Those Who Identify as Black, Indigenous, and People of Color.

BACKGROUND: In the third quarter of 2021, government entities enacted vaccine requirements across multiple employment sectors, including healthcare. Experience from previous vaccination campaigns within healthcare emphasize the need to translate community modalities of vaccine outreach and education that partner with Black communities, Indigenous communities, and communities of Color stakeholders to increase vaccine confidence broadly. METHODS: This was an observational feasibility study conducted from August through October 2021 that deployed and measured the effect of a multimodal approach to increasing vaccine uptake in healthcare employees. Vaccine data were acquired through the Center for Disease Control Immunization Information Systems across Oregon and Washington. Rates of complete vaccination before the intervention were compared with rates after as a measure of feasibility of this intervention. These data were subdivided by race/ethnicity, age, gender, and job class. Complete vaccination was defined as completion of a 2-dose mRNA SARS-CoV-2 vaccine series or a 1-dose adenoviral vector SARS-CoV-2 vaccine. RESULTS: Overall preintervention and postintervention complete vaccination rates were 83.7% and 93.5%, respectively. Of those employees who identified as a certain race, black employees demonstrated the greatest percentage difference increase, 18.5% (preintervention, 72.1%; postintervention, 90.6%), followed by Hispanic employees, 14.1% (preintervention, 79.4%; postintervention, 93.5%), and employees who identify as 2 or more races, 13.9% (preintervention, 78.7%; postintervention, 92.6%). CONCLUSIONS: We found that a multimodal approach to improving vaccination uptake in employees was feasible. For organizations addressing vaccine requirements for their workforce, we recommend a multimodal strategy to increase vaccine confidence and uptake.

Reprogramming the adjuvant properties of aluminum oxyhydroxide with nanoparticle technology.

Aluminum salts, developed almost a century ago, remain the most commonly used adjuvant for licensed human vaccines. Compared to more recently developed vaccine adjuvants, aluminum adjuvants such as Alhydrogel are heterogeneous in nature, consisting of 1-10 micrometer-sized aggregates of nanoparticle aluminum oxyhydroxide fibers. To determine whether the particle size and aggregated state of aluminum oxyhydroxide affects its adjuvant activity, we developed a scalable, top-down process to produce stable nanoparticles (nanoalum) from the clinical adjuvant Alhydrogel by including poly(acrylic acid) (PAA) polymer as a stabilizing agent. Surprisingly, the PAA:nanoalum adjuvant elicited a robust TH1 immune response characterized by antigen-specific CD4+ T cells expressing IFN-γ and TNF, as well as high IgG2 titers, whereas the parent Alhydrogel and PAA elicited modest TH2 immunity characterized by IgG1 antibodies. ASC, NLRP3 and the IL-18R were all essential for TH1 induction, indicating an essential role of the inflammasome in this adjuvant's activity. Compared to microparticle Alhydrogel this nanoalum adjuvant provided superior immunogenicity and increased protective efficacy against lethal influenza challenge. Therefore PAA:nanoalum represents a new class of alum adjuvant that preferentially enhances TH1 immunity to vaccine antigens. This adjuvant may be widely beneficial to vaccines for which TH1 immunity is important, including tuberculosis, pertussis, and malaria.

Adsorption of a synthetic TLR7/8 ligand to aluminum oxyhydroxide for enhanced vaccine adjuvant activity: A formulation approach.

For nearly a century, aluminum salts have been the most widely used vaccine adjuvant formulation, and have thus established a history of safety and efficacy. Nevertheless, for extremely challenging disease targets such as tuberculosis or HIV, the adjuvant activity of aluminum salts may not be potent enough to achieve protective efficacy. Adsorption of TLR ligands to aluminum salts facilitates enhanced adjuvant activity, such as in the human papilloma virus vaccine Cervarix®. However, some TLR ligands such as TLR7/8 agonist imidazoquinolines do not efficiently adsorb to aluminum salts. The present report describes a formulation approach to solving this challenge by developing a lipid-based nanosuspension of a synthetic TLR7/8 ligand (3M-052) that facilitates adsorption to aluminum oxyhydroxide via the structural properties of the helper lipid employed. In immunized mice, the aluminum oxyhydroxide-adsorbed formulation of 3M-052 enhanced antibody and TH1-type cellular immune responses to vaccine antigens for tuberculosis and HIV.

Optimizing manufacturing and composition of a TLR4 nanosuspension: physicochemical stability and vaccine adjuvant activity.

BACKGROUND: Nanosuspensions are an important class of delivery system for vaccine adjuvants and drugs. Previously, we developed a nanosuspension consisting of the synthetic TLR4 ligand glucopyranosyl lipid adjuvant (GLA) and dipalmitoyl phosphatidylcholine (DPPC). This nanosuspension is a clinical vaccine adjuvant known as GLA-AF. We examined the effects of DPPC supplier, buffer composition, and manufacturing process on GLA-AF physicochemical and biological activity characteristics. RESULTS: DPPC from different suppliers had minimal influence on physicochemical and biological effects. In general, buffered compositions resulted in less particle size stability compared to unbuffered GLA-AF. Microfluidization resulted in rapid particle size reduction after only a few passes, and 20,000 or 30,000 psi processing pressures were more effective at reducing particle size and recovering the active component than 10,000 psi. Sonicated and microfluidized batches maintained good particle size and chemical stability over 6 months, without significantly altering in vitro or in vivo bioactivity of GLA-AF when combined with a recombinant malaria vaccine antigen. CONCLUSIONS: Microfluidization, compared to water bath sonication, may be an effective manufacturing process to improve the scalability and reproducibility of GLA-AF as it advances further in the clinical development pathway. Various sources of DPPC are suitable to manufacture GLA-AF, but buffered compositions of GLA-AF do not appear to offer stability advantages over the unbuffered composition.

Charged aerosol detection to characterize components of dispersed-phase formulations.

Colloidal formulations based on biocompatible phospholipids, emulsifiers, and oils are employed in a wide range of applications including medicine, food, and cosmetics. However, characterization of these dispersed-phase components may be difficult to analyze by traditional HPLC with UV, visible, or fluorescence detection modalities due to lack of chromophores or fluorophores. Charged aerosol detection (CAD) is increasingly used for analysis of dispersed-phase components due to its broad applicability and high sensitivity for non-chromophore containing components found in many colloidal systems, such as lipid-based molecules. In this review, we summarize the recent applications of CAD reported in the literature as well as our own laboratory for the analysis of widely used components of dispersed-phase systems. In particular, we discuss the advantages and disadvantages of CAD compared to other HPLC detection methods, as well as the various sample preparation methods suitable for colloidal formulations prior to HPLC-CAD analysis.