High Degree Of Immunogenicity Research Articles

Immunogenicity assessment of fungal l-asparaginases: an in silico approach

Acute lymphoblastic leukemia is the most common cancer among children worldwide, characterized by an overproduction of undifferentiated lymphoblasts in the bone marrow. The enzyme l-asparaginase isolated from Escherichia coli and Dickeya chrysanthemi is a key factor in multiple therapies against this disease. Regardless of their effectiveness, these formulations present well-known adverse effects, highlighting the immunogenicity and allergenicity they cause. Some strategies have been adopted in this regard, such as PEGylation and modification by bioengineering as well as the search for new non-bacterial microorganisms producing the enzyme. Fungi have been shown to be asparaginase producers with high antitumor activity; however, little is known about the immunological features of fungal asparaginase. In this work, we developed the first immunoinformatics study focused on revealing the antigenic determinants that contribute to the immunogenicity of nine asparaginases of filamentous fungi experimentally tested, and compared them with the enzyme from E. coli. We were able to predict that the fungal asparaginases evaluated have a high degree of immunogenicity, which is an important result to consider if the aim is to produce clinical l-asparaginase from a fungal source. Likewise, for the first time, a bioinformatics-based approach was used to predict the immunogenic and allergenic epitopes present in fungal asparaginases.

Novel anti-melanoma treatment: focus on immunotherapy.

Melanoma is an intractable cancer that is aggressive, lethal, and metastatic. The prognosis of advanced melanoma is very poor because it is insensitive to chemotherapy and radiotherapy. The incidence of melanoma has been ascending stably for years worldwide, accompanied by increasing mortality. New approaches to managing this deadly disease are much anticipated to enhance the cure rate and to extend clinical benefits to patients with metastatic melanoma. Due to its high degree of immunogenicity, melanoma could be a good target for immunotherapy, which has been developed for decades and has achieved certain progress. This article provides an overview of immunotherapy for melanoma.

Conserved regions of Plasmodium vivax potential vaccine candidate antigens in Sri Lanka: Conscious in silico analysis of prospective conformational epitope regions

ObjectivesTo do mapping and modeling of conformational B cell epitope regions of highly conserved and protective regions of three merozoitecandidate vaccine proteins of Plasmodium vivax (P. vivax), ie. merozoite purface protein-1 (PvMSP-1), apical membrane antigen −1 domain ∏ (PvAMA1-D∏) and region ∏ of the Duffy binding protein (PvDBP∏), and to analyze the immunogenic properties of these predicted epitopes. Methods3-D structures of amino acid haplotypes from Sri Lanka (available in GeneBank) of PvMSP-119 (n=27), PvAMA1-D∏ (n=21) and PvDBP∏ (n=33) were modeled. SEPPA, selected as the best online server was used for conformational epitope predictions, while prediction and modeling of protein structure and properties related to immunogenicity was carried out with Geno3D server, SCRATCH Protein Server, NetSurfP Server and standalonesoftware, Genious 5.4.4. ResultsSEPPA revealed that regions of predicted conformational epitopes formed 4 clusters in PvMSP-I19, and 3 clusters each in PvAMA1-D∏ and PvDBP∏, all of which displayed a high degree of hydrophilicity, contained solvent exposed residues, displayed high probability of antigenicity and showed positive antigenic propensity values, that indicated high degree of immunogenicity. ConclusionsFindings of this study revealed and confirmed that different parts of the sequences of each of the conserved regions of the three selected potential vaccine candidate antigens of P. vivax are important with regard to conformational epitope prediction that warrants further laboratory experimental investigations in in vivo animal models.

Lentiviral vectors for HIV disease prevention and treatment

HIV/AIDS has posed major challenges to the scientific community, both in terms of treatment and prevention. Current drug regimens, while efficacious, are expensive, inaccessible to major parts of the world, induce major side effects, and cannot prevent escape mutants due to lack of compliance and drug fatigue. In the vaccine field, recent setbacks related to the interruption and cancellation of major advanced clinical trials using adenoviral vectors have highlighted the need for new and innovative strategies. Unique features of HIV-based lentiviral vectors (LVs) and the current progress in the LV-based platform development make them an attractive alternative for the further LV-based HIV vaccine development. In preclinical studies, they have demonstrated a high degree of immunogenicity, while overcoming pitfalls faced by other viral vectors. These findings, combined with recent progress in large scale LV production/purification, make this strategy worth considering for further vaccine development.

A subset of porcine reproductive and respiratory syndrome virus GP3 glycoprotein is released into the culture medium of cells as a non-virion-associated and membrane-free (soluble) form.

The GP3 protein of the IAF-Klop strain of porcine reproductive and respiratory syndrome virus (PRRSV) was expressed in 293 cells by a recombinant human type 5 adenovirus carrying the open reading frame 3 gene. The protein exhibited a molecular mass of 42 kDa and comigrated with GP3 expressed in PRRSV-infected MARC-145 cells. Removal of N-linked glycans from GP3 resulted in a 27-kDa protein (P3), confirming its highly glycosylated nature. Pulse-chase experiments carried out either in the context of PRRSV infection or upon individual expression of GP3 in 293 cells showed that the protein remains completely endo-beta-N-acetylglucosaminidase H-sensitive even after 4 h of synthesis. Thus, the transport of GP3 was restricted to the premedial Golgi compartment, presumably the endoplasmic reticulum (ER). However, a minor fraction of GP3 was found to be secreted in the culture medium as a soluble membrane-free form. This released protein (sGP3) was readily identified upon individual expression of GP3 in 293 cells as well as in the context of PRRSV infection, albeit at lower levels. The sGP3 migrated as a smear and displayed a molecular mass ranging from 43 to 53 kDa. The unglycosylated form of sGP3 comigrated with its intracellular deglycosylated counterpart, suggesting that the release from the cell of a subset of GP3 did not result from cleavage of a putative membrane-anchor sequence. Strikingly, unlike GP3, the sGP3 acquired Golgi-specific modifications of its carbohydrate side chains and folded into a disulfide-linked homodimer. Brefeldin A treatment completely abolished the release of sGP3, suggesting that the ER-to-Golgi compartment is an obligatory step in cellular secretion of sGP3. In contrast, 10 mM monensin did not prevent sGP3 release but inhibited the terminal glycosylation that confers on the protein its diffuse pattern. Since GP3 was found to be nonstructural in the case of the North American strain, secretion of a minor fraction of GP3 might be an explanation for its high degree of immunogenicity in infected pigs. Furthermore, this secreted protein might be relevant as a model for further studies on the cellular subcompartments involved in the sorting of proteins to the extracellular milieu.