Lipid nanoparticles enhance the efficacy of mRNA and protein subunit vaccines by inducing robust T follicular helper cell and humoral responses.

Adjuvants are critical for improving the quality and magnitude of adaptive immune responses to vaccination. Lipid nanoparticle (LNP)-encapsulated nucleoside-modified mRNA vaccines have shown great efficacy against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), but the mechanism of action of this vaccine platform is not well-characterized. Using influenza virus and SARS-CoV-2 mRNA and protein subunit vaccines, we demonstrated that our LNP formulation has intrinsic adjuvant activity that promotes induction of strong T follicular helper cell, germinal center B cell, long-lived plasma cell, and memory B cell responses that are associated with durable and protective antibodies in mice. Comparative experiments demonstrated that this LNP formulation outperformed a widely used MF59-like adjuvant, AddaVax. The adjuvant activity of the LNP relies on the ionizable lipid component and on IL-6 cytokine induction but not on MyD88- or MAVS-dependent sensing of LNPs. Our study identified LNPs as a versatile adjuvant that enhances the efficacy of traditional and next-generation vaccine platforms.

The oral vaccine based on self-replicating RNA lipid nanoparticles can simultaneously neutralize both SARS-CoV-2 variants alpha and delta.

The aim of this study was to evaluate self-replicating RNA lipid nanoparticles (saRNA LNPs) to neutralize SARS-CoV-2 variants delta (B.1.617 lineage) and alpha (B.1.1.7 lineage). Before immunization of mice with saRNA LNPs, we saw high expression of S-protein at both mRNA and protein levels after transfection of HEK293T/17 cells with saRNA LNPs. After oral immunization of BALB/c mice with 0.1 - 10 µg saRNA LNPs , a high quantity of SARS-CoV-2 specific IgG and IgA antibodies were seen with a dose-dependent pattern. Importantly, the ratio of IgG2a/IgG1 in serum of vaccinated mice showed Th1/Th2 skewing response. We also found that the secreted antibodies could neutralize SARS-CoV-2 variants delta (B.1.617 lineage) and alpha (B.1.1.7 lineage). Re-stimulated splenocytes of vaccinated mice showed high secretion of IFN-γ, IL-6, and TNF- α . The authors think that although the preclinical study confirmed the efficacy of saRNA LNPs against SARS-CoV-2, the actual efficacy and safety of the oral vaccine must be evaluated in clinical trials.

COVID-19 vaccine race: watch your step for cancer patients.

Patients with cancer should benefit from COVID-19 vaccination. Some of the most advanced vaccine candidates are mRNAs encapsulated into lipid carriers, and small liposomes are expected to accumulate in tumour tissues through the enhanced and permeation retention effect. However, to what extent solid tumours could take up a significant part of the vaccine dose as well remains unknown. This calls for a careful evaluation of the efficacy of these promising mRNA COVID-19 vaccines administered as lipid carriers for patients with solid tumours, including a possible re-appraisal of the dosing for optimal protection of this specific and frail population.

Development of Provesicular Nanodelivery System of Curcumin as a Safe and Effective Antiviral Agent: Statistical Optimization, In Vitro Characterization, and Antiviral Effectiveness.

Curcumin is a natural compound that has many medical applications. However, its low solubility and poor stability could impede its clinical applications. The present study aimed to formulate dry proniosomes to overcome these pitfalls and improve the therapeutic efficacy of Curcumin. Curcumin-loaded proniosomes were fabricated by the slurry method according to 32 factorial design using Design-Expert software to demonstrate the impact of different independent variables on entrapment efficiency (EE%) and % drug released after 12 h (Q12h). The optimized formula (F5) was selected according to the desirability criteria. F5 exhibited good flowability and appeared, after reconstitution, as spherical nanovesicles with EE% of 89.94 ± 2.31% and Q12h of 70.89 ± 1.62%. F5 demonstrated higher stability and a significant enhancement of Q12h than the corresponding niosomes. The docking study investigated the ability of Curcumin to bind effectively with the active site of DNA polymerase of Herpes simplex virus (HSV). The antiviral activity and the safety of F5 were significantly higher than Curcumin. F5 improved the safety of Acyclovir (ACV) and reduced its effective dose that produced a 100% reduction of viral plaques. Proniosomes could be promising stable carriers of Curcumin to be used as a safe and efficient antiviral agent.