A potential bivalent mRNA vaccine candidate protects against both RSV and SARS-CoV-2 infections.

As the world continues to confront severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), respiratory syncytial virus (RSV) is also causing severe respiratory illness in millions of infants, elderly individuals, and immunocompromised people globally. Exacerbating the situation is the fact that co-infection with multiple viruses is occurring, something which has greatly increased the clinical severity of the infections. Thus, our team developed a bivalent vaccine that delivered mRNAs encoding SARS-CoV-2 Omicron spike (S) and RSV fusion (F) proteins simultaneously, SF-LNP, which induced S and F protein-specific binding antibodies and cellular immune responses in BALB/c mice. Moreover, SF-LNP immunization effectively protected BALB/c mice from RSV infection and hamsters from SARS-CoV-2 Omicron infection. Notably, our study pointed out the antigenic competition problem of bivalent vaccines and provided a solution. Overall, our results demonstrated the potential of preventing two infectious diseases with a single vaccine and provided a paradigm for the subsequent design of multivalent vaccines.

Long-term immune response to Omicron-specific mRNA vaccination in mice, hamsters, and nonhuman primates.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron and its subvariants (such as BQ.1, XBB and the latest variants, including XBB.1.16, EG.5, and BA.2.86), as the dominant variants, currently account for almost all new infections in the world due to their high transmissibility and immune escape ability. Omicron-specific mRNA vaccines showed great potential to protect against Omicron infections. However, whether the vaccine could provide long-term protection is unknown. Toward this goal, we evaluated the immunogenicity of a preclinical Omicron (BA.1)-specific mRNA vaccine (SOmicron-6P) in different animal models. SOmicron-6P induced the highest levels of antibody titers at 1-2 weeks in different animals after the second dose. Even 9 months after the immunization, we observed modest neutralizing activity against Omicron subvariants in macaques. In addition, immunological memory cells can be rapidly reactivated upon stimulation. SOmicron-6P at concentrations higher than 10 µg effectively protected hamsters from BA.1 challenge 253 days after the first immunization, which could be attributed to the reactivation of immune systems. In addition, the toxicity tests conducted in rats revealed a highly favorable biosafety profile for SOmicron-6P, even at high dosages. Our data suggest that the Omicron-specific mRNA vaccine is highly effective and safe in animal models and provides long-term immunologic protection against SARS-CoV-2 Omicron infections.

Pathogen Recognition-Driven Dendritic Cell-Specific Gene Silencing and Editing.

Dendritic cells (DCs) play an essential role in both the induction of the immune response and the maintenance of immune tolerance, with any malfunction of DCs potentially causing several diseases. While gene-based therapy for DC manipulation is a promising approach, it remains challenging due to the lack of efficient delivery systems for DC targeting. Herein, we describe a novel bacterial nanomedicine (BNM) system for pathogen recognition-mediated DCs-specific gene silencing and gene editing. BNMs contain components from bacterial outer membranes and achieve efficient DC targeting through the recognition of pathogen-associated molecular patterns by pattern recognition receptors on DCs. The targeting efficiency of BNMs is reduced in DCs lacking toll-like receptor 4, which is responsible for recognizing lipopolysaccharide, a major component of the bacterial outer membrane. As a proof-of-concept demonstration, we present gene-based therapy mediated by BNMs for enhancing antigen cross-presentation in DCs, which generates a remarkable antitumor effect.

Protective effect of teprenone on gastric mucosal injury induced by dual antiplatelet therapy in rats.

OBJECTIVE: To investigate the protective effect of teprenone on gastric mucosal injury induced by dual antiplatelet therapy in rats. METHODS: Healthy, specifically pathogen free SD, rats were selected and divided into 4 groups: Normal group (normal rats, without any treatment), Model group (rats received dual antiplatelet therapy: aspirin and clopidogrel), Teprenone group (rats received dual antiplatelet therapy and teprenone) and Pantoprazole group (rats received dual antiplatelet therapy and pantoprazole). The gastric mucosal blood flow, ulcer index, gastric gel mucus thickness, the levels of gastrin (Gas), prostaglandin (PG), prostaglandin E2 (PGE2), endothelin-1 (ET-1) tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, IL-6 and IL-10 in serum, the levels of malondialdehyde (MDA), glutathione (GSH), superoxide dismutase (SOD) and myeloperoxidase (MPO) in the gastric mucosa, as well as the expression of vascular endothelial growth factor (VEGF) in the rat's stomach were measured. RESULTS: Compared with the Normal group, the other groups showed more severe gastric injury, elevated levels of inflammatory factors (TNF-α, IL-1ß, IL-6 and IL-10), elevated levels of MDA and MPO, as well as reduced levels of GSH, SOD and VEGF (all P<0.05). Compared with the Model group, the gastric mucosal lesions in the Teprenone group and the Pantoprazole group were improved significantly (both P<0.05). Compared with the Pantoprazole group, the Teprenone group had reduced levels of ET-1 and elevated levels of PG and PGE2 (all P<0.05). CONCLUSION: Teprenone protects against gastric mucosal injury induced by dual antiplatelet therapy through inhibiting gastric mucosal inflammation inhibiting oxidative stress and improving gastric mucosa indices.

Silica-polydopamine hybrids as light-induced oxidase mimics for colorimetric detection of pyrophosphate.

In this study, silica-polydopamine hybrids (SPDA) were fabricated by a facile and one-step heating method using dopamine and (3-aminopropyl)triethoxysilane (APTES) as the reaction reagents. It was firstly found that light illuminated-SPDA could oxidize colorless 3,3',5,5'-tetramethylbenzidine (TMB) to produce blue ox-TMB. The coloration process was quenched very efficiently via the addition of Cu2+. The presence of pyrophosphate ion (PPi) in the solution of light-illuminated SPDA-Cu2+-TMB induced the recovery of the coloration process. The recovery occurred because PPi coordinated with Cu2+, effectively sequestering the ion from SPDA. A calibration curve was developed that is related to the extent of absorption recovery to [PPi], making the SPDA-Cu2+-TMB system a sensitive and selective turn-on sensor for PPi detection. The limit-of-detection (LOD) for PPi was 0.06 µmol L-1 (S/N = 3) with a linear dynamic range of 0.1-30 µmol L-1 and the calibration curve of linear equation is given as: y = 0.00146x + 0.05096 (r = 0.9974). The proposed method has been successfully applied to the detection of PPi in human serum with satisfactory recovery. The simplicity, low cost, high sensitivity, good reproducibility and excellent selectivity of the PPi detection platform based on the light-induced oxidase mimicking property of SPDA makes it promising for further applications of SPDA in chemo/biosensing.

A robust and versatile signal-on fluorescence sensing strategy based on SYBR Green I dye and graphene oxide.

A robust and versatile signal-on fluorescence sensing strategy was developed to provide label-free detection of various target analytes. The strategy used SYBR Green I dye and graphene oxide as signal reporter and signal-to-background ratio enhancer, respectively. Multidrug resistance protein 1 (MDR1) gene and mercury ion (Hg(2+)) were selected as target analytes to investigate the generality of the method. The linear relationship and specificity of the detections showed that the sensitive and selective analyses of target analytes could be achieved by the proposed strategy with low detection limits of 0.5 and 2.2 nM for MDR1 gene and Hg(2+), respectively. Moreover, the strategy was used to detect real samples. Analytical results of MDR1 gene in the serum indicated that the developed method is a promising alternative approach for real applications in complex systems. Furthermore, the recovery of the proposed method for Hg(2+) detection was acceptable. Thus, the developed label-free signal-on fluorescence sensing strategy exhibited excellent universality, sensitivity, and handling convenience.