Current Issue : January - March Volume : 2021 Issue Number : 1 Articles : 5 Articles
Peptide vaccines are safe, and aim to elicit and expand tumor-specific immunity so as to\neradicate tumors. However, achieving strong and long-lasting anti-tumor immunity with peptide\nvaccines for the antigen-specific treatment of cancer is challenging, in part because their efficacy\ndepends on strong adjuvants or immunomodulators. We approached this problem by conjugating\nan epitope-based cancer vaccine with a lipidated sequence (an immunomodulator) to elicit a strong\nimmune response. Lipidated and non-lipidated polyepitope proteins were generated that contained\nthe universal T helper cell epitope (pan-DR), B cell epitopes, and the extended loop sequence of\nextracellular domain 2 of tumor-associated antigen L6 (TAL6). We show that the lipidated polyepitope\ncancer vaccine can activate bone marrow-derived dendritic cells, and trigger effective antigen-specific\nantibody and T helper cell responses, more effectively than the non-lipidated vaccine. Moreover,\npotent T cell immune responses were elicited in mice inoculated with the lipidated polyepitope\ncancer vaccine, providing protective antitumor immunity in mice bearing TAL6 tumors. Our study\ndemonstrates that a lipidated polyepitope cancer vaccine could be employed to generate potent\nanti-tumor immune responses, including humoral and cellular immunity, which could be beneficial\nin the treatment of TAL6+ cancer....
The embryonated egg-based platform currently produces the majority of seasonal influenza\nvaccines by employing a well-developed master donor virus (MDV, A/PR/8/34 (PR8)) to generate\nhigh-growth reassortants (HGRs) for A/H1N1 and A/H3N2 subtypes. Although the egg-based\nplatform can supply enough seasonal influenza vaccines, it cannot meet surging demands during\ninfluenza pandemics. Therefore, multi-purpose platforms are desirable for pandemic preparedness.\nThe Vero cell-based production platform is widely used for human vaccines and could be a potential\nmulti-purpose platform for pandemic influenza vaccines. However, many wild-type and egg-derived\ninfluenza viruses cannot grow efficiently in Vero cells. Therefore, it is critical to develop Vero\ncell-derived high-growth MDVs for pandemic preparedness. In this study, we evaluated two in-house\nMDVs (Vero-15 and VB5) and two external MDVs (PR8 and PR8-HY) to generate Vero cell-derived\nHGRs for five avian influenza viruses (AIVs) with pandemic potentials (H5N1 clade 2.3.4, H5N1 clade\n2.3.2.1, American-lineage H5N2, H7N9 first wave and H7N9 fifth wave). Overall, no single MDV\ncould generate HGRs for all five AIVs, but this goal could be achieved by employing two in-house\nMDVs (vB5 and Vero-15). In immunization studies, mice received two doses of Vero cell-derived\ninactivated H5N1 and H7N9 whole virus antigens adjuvanted with alum and developed robust\nantibody responses....
Human parechovirus type 3 (HPeV3) is an etiologic agent of respiratory diseases, meningitis,\nand sepsis-like illness in both infants and adults. Monoclonal antibodies (mAbs) can be a promising\ndiagnostic tool for antigenic diseases such as virus infection, as they offer a high specificity toward a\nspecific viral antigen. However, to date, there is no specific mAb available for the diagnosis of HPeV3\ninfection. In this study, we developed and characterized mAbs specific for HPeV3 capsid protein VP0.\nWe used cell-free, wheat germ-synthesized viral VP0 protein for immunizing BALB/c mice to generate\nhybridomas. From the resultant hybridoma clones, we selected nine clones producing mAbs reactive\nto the HPeV3-VP0 antigen, based on enzyme-linked immunosorbent assay (ELISA). Epitope mapping\nshowed that these mAbs recognized three distinct domains in HPeV3 VP0. Six mAbs recognized\nHPeV3 specifically and the other three mAbs showed cross-reactivity with other HPeVs. Using the\nHPeV3-specific mAbs, we then developed an ELISA for viral antigen detection that could be reliably\nused for laboratory diagnosis of HPeV3. This ELISA system exhibited no cross-reactivity with other\nrelated viruses. Our newly developed mAbs would, thus, provide a useful set of tools for future\nresearch and ensure HPeV3-specific diagnosis....
About 40-70% of drug molecules in the clinical development pipeline suffer from one of\neither low aqueous solubility, poor absorption, or extremely low bioavailability. Approximately 75%\nof the world population relies on traditional therapies and therefore there has been a growing interest\nin the utilization of natural compounds. Zerumbone is one such natural compound, classified as a\nsesquiterpenoid that is extracted from the essential volatile oils of rhizomes from Zingiber zerumbet.\nIt possesses strong antitumor, antioxidant, antimicrobial, and anti-inflammatory activity. However,\ndespite promising preclinical studies demonstrating the therapeutic utility of zerumbone, its clinical\ndevelopment has been limited due to its low aqueous solubility, poor absorption, or associated low\nbioavailability. Multiple reviews demonstrating the pharmacological effects of zerumbone for various\ndiseases have been published. However, to our knowledge, no review demonstrates the various\nformulation strategies developed to overcome the biopharmaceutical challenges of zerumbone.\nThe purpose of this review is to provide a comprehensive perspective on zerumbone as a molecule for\nformulation development. A section related to pharmacokinetics, toxicity, and patents of zerumbone\nis included. This review provides the importance of developing novel formulations of zerumbone\nto overcome its biopharmaceutical challenges thereby advance its potential in the treatment of\nvarious diseases....
A worrisome trend in the study and treatment of infectious disease noted in recent years is\nthe increase in multidrug resistant strains of bacteria concurrent with a scarcity of new antimicrobial\nagents to counteract this rise. This is particularly true amongst bacteria within the Enterococcus\nfaecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa,\nand Enterobacter species (ESKAPE) designation. P. aeruginosa is one of the most common causes\nof bacterial keratitis. Therefore, it is of vital importance to characterize new antimicrobial agents\nwith anti-Pseudomonal activity for use with the ocular surface. MEDI3902 is a multifunctional\nantibody that targets the P. aeruginosa persistence factor Psl exopolysaccharide, and the type 3 secretion\nprotein PcrV. We initially assessed this antibody for ocular surface toxicity. The antimicrobial activity\nof the antibody was then tested by treating mice with established P. aeruginosa keratitis with both\ntopical and intravenous treatment modalities. MEDI3902, was shown to be non-toxic to the ocular\nsurface of mice when given topically. It was also effective compared to the control antibody at\npreventing P. aeruginosa keratitis with a one-time treatment at the time of infection. Both topical and\nintravenous administration of MEDI3902 has been proved significant in treating established keratitis\ninfections as well, speeding the resolution of infection significantly more than that of the control IgG.\nWe report the first use of a topical immunotherapeutic multifunctional agent targeting Psl and type\n3 secretion on the ocular surface as an antimicrobial agent. While MEDI3902 has been shown to\nprevent Pseudomonas biofilm formation in keratitis models when given prophylactically intravitally,\nwe show that MEDI3902 has the capability to also treat an active infection when given intravenously\nto mice with Pseudomonas keratitis. Our data indicate antibodies are well tolerated and nontoxic on\nthe ocular surface. They reduce infection in mice treated concurrently at inoculation and reduced\nthe signs of cornea pathology in mice with established infection. Taken together, these data indicate\ntreatment with monoclonal antibodies directed against Psl and PcrV may be clinically effective in the\ntreatment of P. aeruginosa keratitis and suggest that the design of further antibodies to be an additional\ntool in the treatment of bacterial keratitis....
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