A Multi-Targeting,Nucleoside-Modified mRNA Influenza Virus Vaccine Provides Broad Protection in Mice

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Lipid-nanoparticle-encapsulated mRNA vaccines induce protective memory CD8 T cells against a lethal viral infection

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Lipid-nanoparticle-encapsulated mRNA vaccines induce protective memory CD8 T cells against a lethal viral infection

It is well established that memory CD8 T cells protect susceptible strains of mice from mousepox, a lethal viral disease caused by ectromelia virus (ECTV), the murine counterpart to human variola virus. While mRNA vaccines induce protective antibody (Ab) responses, it is unknown whether they also induce protective memory CD8 T cells. We now show that immunization with different doses of unmodified or N(1)-methylpseudouridine-modified mRNA (modified mRNA) in lipid nanoparticles (LNP) encoding the ECTV gene EVM158 induced similarly strong CD8 T cell responses to the epitope TSYKFESV, albeit unmodified mRNA-LNP had adverse effects at the inoculation site. A single immunization with 10 μg modified mRNA-LNP protected most susceptible mice from mousepox, and booster vaccination increased the memory CD8 T cell pool, providing full protection. Moreover, modified mRNA-LNP encoding TSYKFESV appended to green fluorescent protein (GFP) protected against wild-type ECTV infection while lymphocytic choriomeningitis virus glycoprotein (GP) modified mRNA-LNP protected against ECTV expressing GP epitopes. Thus, modified mRNA-LNP can be used to create protective CD8 T cell-based vaccines against viral infections.     

Development of an mRNA-lipid nanoparticle vaccine against Lyme disease

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Bacteria-enabled oral delivery of a replicon-based mRNA vaccine candidate protects against ancestral and delta variant SARS-CoV-2

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A self-amplifying mRNA SARS-CoV-2 vaccine candidate induces safe and robust protective immunity in preclinical models

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Modern lipid‐, carbohydrate‐, and peptide‐based delivery systems for peptide,vaccine, and gene products

Research related to peptide, vaccine, and gene delivery has grown exponentially over the last decade. In this review, we discuss the development of delivery systems for peptides, gene and vaccine products. Special focus is given to different lipidation and glycosylation strategies to improve the metabolic stability and membrane permeability of therapeutics, and their targeting to specific sites. The synthetic methods for preparation of the systems are also described. © 2009 Wiley Periodicals, Inc. Med Res Rev, 31, No. 4, 520–547, 2011     

Accelerated DNA vaccine regimen provides protection against Crimean-Congo hemorrhagic fever virus challenge in a macaque model

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青蒿素固体脂质纳米粒冻干剂的体外释药性质研究

目的探讨青蒿素固体脂质纳米粒（ART—SLN）的体外释药性质。方法采用动态透析法测定释药介质中的青蒿素累计释放含量,并用不同的数学模型模拟释放行为。结果青蒿素在乙醇溶液中的溶出曲线采用Weibull方程拟合效果最佳。结论ART—SLN具一定缓释作用,达到预期目标。     

CIMAvax-EGF,a therapeutic non-small cell lung cancer vaccine

Introduction: Lung cancer represents the most common cause of cancer death worldwide. While the prognosis remains poor, immunotherapy is giving a positive impact on survival. Cancer vaccines represent a form of active immunotherapy that historically has given modest results in terms of efficacy.

The overexpression of the EGFR by tumor cells was reported in more than half of cases of lung cancer, representing a mechanism of cancerogenesis. CIMAvax-EGF, a therapeutic vaccine for non-small cell lung cancer (NSCLC) developed in Cuba, consists of a human recombinant EGF able to induce antibodies against the autologous EGF, resulting in serum EGF withdrawal and lower EGF-EGFR interaction.

Area covered: We critically reviewed the existing literature about CIMAvax-EGF, from the Pilot studies to the efficacy controlled studies. We also overviewed the ongoing trials.

Expert opinion: CIMAvax-EGF demonstrated to be safe and immunogenic. In a phase III randomized study CIMAvax-EGF, used as a switch maintenance treatment after platinum-based chemotherapy, did not significantly improve survival. Current data are not sufficient to recommend CIMAvax-EGF as a treatment option for advanced stage NSCLC. Further studies, conducted in a context of worldwide standardized clinical practice, are needed to better define if a subpopulation of patients can benefit from the vaccination.     

Delivery of a cocktail DNA vaccine encoding cysteine proteinases type I, II and III with solid lipid nanoparticles potentiate protective immunity against Leishmania major infection

Earlier generations of Leishmania vaccines have reached the third-phase of clinical trials, however none of them have shown adequate efficacy due to lack of an appropriate adjuvant. In this study, cationic solid lipid nanoparticles (cSLNs) were used to formulate three pDNAs encoding L. major cysteine proteinase type I (cpa), II (cpb) and III (cpc). BALB/c mice were immunized twice with a 3-week interval, with SLN-pcDNA-cpa/b/c, pcDNA-cpa/b/c, SLN, SLN-pcDNA and PBS. Footpad assessments, parasite burden, cytokine and antibody responses were evaluated. Mice vaccinated with SLN-pcDNA-cpa/b/c significantly (p < 0.05) showed higher protection levels with specific Th1 immune response development compared to other groups. This is the first report demonstrating cSLNs as a nanoscale vehicle boosting immune response quality and quantity; in a designable trend. The nanomedical feature of this novel formulation can be applied for wide-spread use in genetic vaccination against leishmaniasis, which is currently managed only through relatively ineffectual therapeutic regimens.     

Prospects for and barriers to a fungal vaccine

Vaccination is a desirable strategy to prevent life-threatening fungal infections. Candidiasis is the most common invasive fungal infection, and promising vaccine targets are nearing clinical testing to prevent such infections. One barrier to developing antifungal vaccines is the perceived risk of blunted immune responses in at-risk patients. However, vaccines stimulate effective immune responses even in highly immunocompromised patients. The biggest barrier to development of fungal vaccines is the lack of available capital to translate discoveries made at the bench into biologics used at the bedside. Nevertheless, vaccines targeting invasive fungal infections are an extremely promising avenue of research and development. It is desirable that additional sources of capital be made available to academic scientists to facilitate development of such vaccines.