A SARS-CoV-2 RBD vaccine fused to the chemokine MIP-3α elicits sustained murine antibody responses over 12 months and enhanced lung T-cell responses.

Background: Previous studies have demonstrated enhanced efficacy of vaccine formulations that incorporate the chemokine macrophage inflammatory protein 3α (MIP-3α) to direct vaccine antigens to immature dendritic cells. To address the reduction in vaccine efficacy associated with a mutation in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mutants, we have examined the ability of receptor-binding domain vaccines incorporating MIP-3α to sustain higher concentrations of antibody when administered intramuscularly (IM) and to more effectively elicit lung T-cell responses when administered intranasally (IN). Methods: BALB/c mice aged 6-8 weeks were immunized intramuscularly or intranasally with DNA vaccine constructs consisting of the SARS-CoV-2 receptor-binding domain alone or fused to the chemokine MIP-3α. In a small-scale (n = 3/group) experiment, mice immunized IM with electroporation were followed up for serum antibody concentrations over a period of 1 year and for bronchoalveolar antibody levels at the termination of the study. Following IN immunization with unencapsulated plasmid DNA (n = 6/group), mice were evaluated at 11 weeks for serum antibody concentrations, quantities of T cells in the lungs, and IFN-γ- and TNF-α-expressing antigen-specific T cells in the lungs and spleen. Results: At 12 months postprimary vaccination, recipients of the IM vaccine incorporating MIP-3α had significantly, approximately threefold, higher serum antibody concentrations than recipients of the vaccine not incorporating MIP-3α. The area-under-the-curve analyses of the 12-month observation interval demonstrated significantly greater antibody concentrations over time in recipients of the MIP-3α vaccine formulation. At 12 months postprimary immunization, only recipients of the fusion vaccine had concentrations of serum-neutralizing activity deemed to be effective. After intranasal immunization, only recipients of the MIP-3α vaccine formulations developed T-cell responses in the lungs significantly above those of PBS controls. Low levels of serum antibody responses were obtained following IN immunization. Conclusion: Although requiring separate IM and IN immunizations for optimal immunization, incorporating MIP-3α in a SARS-CoV-2 vaccine construct demonstrated the potential of a stable and easily produced vaccine formulation to provide the extended antibody and T-cell responses that may be required for protection in the setting of emerging SARS-CoV-2 variants. Without electroporation, simple, uncoated plasmid DNA incorporating MIP-3α administered intranasally elicited lung T-cell responses.

Factors Affecting the Adsorption of Per- and Polyfluoroalkyl Substances (PFAS) by Colloidal Activated Carbon.

The immobilization of per- and polyfluoroalkyl substances (PFAS) by colloidal activated carbon (CAC) barriers has been proposed as a potential in-situ method to mitigate the transport of plumes of PFAS in the subsurface. However, if PFAS are continuously released from a source zone, the adsorptive sites on CAC will eventually become saturated, upon which point the breakthrough of PFAS in the barrier will occur. To predict the long-term effectiveness of CAC barriers, it is important to evaluate the factors that may affect the adsorption of PFAS on CAC. In this study, the adsorption of 7 PFAS on a polymer-stabilized CAC (i.e., PlumeStop®) and on a polymer-free CAC was investigated using batch experiments. The adsorption affinity of PFAS to CAC was in the following order: PFOS > 6:2 FTS > PFHxS > PFOA > PFBS > PFPeA > PFBA. This result indicates that hydrophobic interaction was the predominant adsorption mechanism, and that hydrophilic compounds such as PFBA and PFPeA will break through CAC barriers first. The partition coefficient Kd for the adsorption of PFAS on the polymer-stabilized CAC was 1.3 - 3.5 times smaller than the Kd for the adsorption of PFAS on the polymer-free CAC, suggesting that the polymers decreased the adsorption, presumably due to competitive sorption. Thus, the PFAS adsorption capacity of PlumeStop CAC barriers is expected to increase once the polymers are biodegraded and/or washed away. The affinity of PFOS and PFOA to CAC increased when the ionic strength of the solution increased from 1 to 100 mM, or when the concentration of Ca2+ increased from 0 to 2 mM. In contrast, less PFOS and PFOA were adsorbed in the presence of 1 - 20 mgC/L Suwannee River Fulvic Acid, which represented dissolved organic carbon, or in the presence of 10 - 100 mg/L diethylene glycol butyl ether (DGBE), which is an important component in some aqueous film-forming foam (AFFF) formulations. The presence of 0.5 - 4.8 mg/L benzene or 0.5 - 8 mg/L trichloroethylene, the co-contaminants that may comingle with PFAS at AFFF-impacted sites, diminished PFOS adsorption but had no effect or even slightly enhanced PFOA adsorption. When the initial concentration of TCE was 8 mg/L, the Kd (514 ± 240 L/g) for the adsorption of PFOS was approximately 20 times lower than that in the TCE-free system (Kd = 9,579 ± 829 L/g). The results of this study provided insights into some key factors that may affect the adsorption of PFAS in in-situ CAC barriers.

In-situ chemical oxidation of chlorendic acid by persulfate: Elucidation of the roles of adsorption and oxidation on chlorendic acid removal.

The oxidation of chlorendic acid (CA), a polychlorinated recalcitrant contaminant, by heat-, mineral-, and base-activated persulfate was investigated. In pH 3-12 homogeneous (i.e., solid-free) solutions, CA was oxidized by •OH and SO4•- radicals, resulting in a nearly stoichiometric production of Cl-. The rate constants for the reaction between these radicals and CA were measured at different temperatures by electron pulse radiolysis, and were found to be kOH = (8.71 ±â€¯0.17) × 107 M-1s-1 and kSO4 = (6.57 ±â€¯0.83) × 107 M-1s-1 at 24.5 °C for •OH and SO4•-, respectively. CA was oxidized at much slower rates in solutions containing iron oxyhydroxide or aquifer soils, partially due to the adsorption of CA on these solids. To gain further insight into the effect of solids during in-situ remediation of CA, the adsorption of CA onto iron (hydr)oxide, manganese dioxide, silica, alumina, and aquifer soils was investigated. The fraction of CA that was adsorbed on these materials increased as the solution pH decreased. Given that the solution pH can decrease dramatically in persulfate-based remedial systems, adsorption may reduce the ability of persulfate to oxidize CA. Overall, the results of this study provide important information about how persulfate can be used to remediate CA-contaminated sites. The results also indicate that the groundwater pH and geology of the subsurface can have a significant influence on the mobility of CA.