An mRNA vaccine candidate encoding cholera toxin subunit B and conserved antigens of influenza viruses confers cross-protection against influenza a viruses in adult and aged mice

Article

作者: Weng, Qian ; Yi, Yongxiang ; Wang, Qin ; Yu, Zhihao ; Li, Junwei ; Xu, Yifan ; Li, Benchi ; Wang, Guiqin ; Xu, Liang

Currently, vaccination with influenza vaccines is still an effective strategy to prevent infection by seasonal influenza virus. However, seasonal influenza vaccines frequently fail to induce effective immune protection against rapidly changing seasonal influenza viruses and emerging zoonotic influenza viruses. In addition, seasonal influenza vaccines may not confer potent protection in elderly and immunocompromised individuals. There is an urgent need to develop potent broad-spectrum influenza vaccines to address this problem. Herein, we designed an mRNA-based broad-spectrum influenza vaccine candidate encoding cholera toxin subunit B and conserved antigens of influenza viruses. In both adult and aged mice, this universal influenza mRNA vaccine candidate stimulated robust T-cell and humoral immune responses and conferred effective protection against broad-spectrum influenza viruses in both adult and aged mice.

2025-03-04·Journal of Biomolecular Structure and Dynamics

Design of a multi-epitope vaccine (vme-VAC/MST-1) against cholera and vibriosis based on reverse vaccinology and immunoinformatics approaches

Article

作者: Soares, Siomar ; Martins, Flaviano S. ; Marques, Pedro Henrique ; Bleicher, Lucas ; Rodrigues, Thais Cristina Vilela ; Aburjaile, Flavia Figueira ; Tiwari, Sandeep ; Oliveira, Carlo Jose Freire ; Santos, Eduardo Horta ; Azevedo, Vasco

Vibriosis and cholera are serious diseases distributed worldwide and caused by six marine bacteria of the Vibrio genus. Thousands of deaths occur each year due to these illnesses, necessitating the development of new preventive measures. Presently, the existing cholera vaccine demonstrates an effectiveness of approximately 60%. Here we describe a new multi-epitope vaccine, 'vme-VAC/MST-1' based on vaccine targets identified by reverse vaccinology and epitopes predicted by immunoinformatics, two currently effective tools for predicting new vaccines for bacterial pathogens. The vaccine was designed to combat vibriosis and cholera by incorporating epitopes predicted for CTL, HTL, and B cells. These epitopes were identified from six vaccine targets revealed through subtractive genomics, combined with reverse vaccinology, and were further filtered using immunoinformatics approaches based on their predicted immunogenicity. To construct the vaccine, 28 epitopes (24 CTL/B and 4 HTL/B) were linked to the sequence of the cholera toxin B subunit adjuvant. In silico analyses indicate that the resulting immunogen is stable, soluble, non-toxic, and non-allergenic. Furthermore, it exhibits no homology to the host and demonstrates a strong capacity to elicit innate, B-cell, and T-cell immune responses. Our analysis suggests that it is likely to elicit immune reactions mediated through the TLR5 pathway, as evidenced by the molecular docking of the vaccine with the receptor, which revealed high affinity and a favorable reaction. Thus, vme-VAC/MST-1 is predicted to be a safe and effective solution against pathogenic Vibrio spp. However, further experimental analyses are required to measure the vaccine's effects In vivo.Communicated by Ramaswamy H. Sarma.

2025-03-01·Ageing Research Reviews

Understanding of Alzheimer's disease pathophysiology for therapeutic implications of natural products as neuroprotective agents

Review

作者: Thakur, Sonu Chand ; Prabha, Sneh ; Islam, Asimul ; Hassan, Md Imtaiyaz ; Choudhury, Arunabh

Alzheimer's disease (AD) is a leading cause of dementia, affecting more than 24.3 million people worldwide in 2024. Sporadic AD (SAD) is more common and occurs in the geriatric population, while familial AD (FAD) is rare and appears before the age of 65 years. Due to progressive cholinergic neuronal loss and modulation in the PKC/MAPK pathway, β-secretase gets upregulated, leading to Aβ aggregation, which further activates tau kinases that form neurofibrillary tangles (NFT). Simultaneously, antioxidant enzymes are also upregulated, increasing oxidative stress (OS) and reactive species by impairing mitochondrial function, leading to DNA damage and cell death. This review discusses the classifications and components of several natural products (NPs) that target these signaling pathways for AD treatment. NPs, including alkaloids, polyphenols, flavonoids, polysaccharides, steroids, fatty acids, tannins, and polypeptides derived from plants, microbes, marine animals, venoms, insects, and mushrooms, are explored in detail. A synergistic combination of plant metabolites, together with prebiotics and probiotics has been shown to decrease Aβ aggregates by increasing the production of bioactive compounds. Toxins derived from venomous organisms have demonstrated effectiveness in modulating signaling pathways and reducing OS. Marine metabolites have also shown neuroprotective and anti-inflammatory properties. The cholera toxin B subunit and an Aβ₁₅ fragment have been combined to create a possible oral AD vaccine, that showed enhancement of cognitive function in mice. Insect tea is also a reliable source of antioxidants. A functional edible mushroom snack bar showed an increment in cognitive markers. Future directions and therapeutic approaches for the treatment of AD can be improved by focusing more on NPs derived from these sources.

100 项与 Cholera toxin B subunit (Istituto Superiore di Sanità) 相关的药物交易

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