The global spread of enteric disease, the increasingly limited options for antimicrobial treatment and the need for effective eradication programs have resulted in an increased demand for glycoconjugate enteric vaccines, made with carbohydrate-based membrane components of the pathogen, and their precise characterisation. A set of physico-chemical and immunological tests are employed for complete vaccine characterisation and to ensure their consistency, potency, safety and stability, following the relevant World Health Organization and Pharmacopoeia guidelines. Variable requirements for analytical methods are linked to conjugate structure, carrier protein nature and size and O-acetyl content of polysaccharide. We investigated a key stability-indicating method which measures the percent free saccharide of Salmonella enterica subspecies enterica serovar Typhi capsular polysaccharide, by detergent precipitation, depolymerisation and HPAEC-PAD quantitation. Together with modern computational approaches, a more precise design of glycoconjugates is possible, allowing for improvements in solubility, structural conformation and stability, and immunogenicity of antigens, which may be applicable to a broad spectrum of vaccines. More validation experiments are required to establish the most effective and suitable methods for glycoconjugate analysis to bring uniformity to the existing protocols, although the need for product-specific approaches will apply, especially for the more complex vaccines. An overview of current and emerging analytical approaches for the characterisation of vaccines against Salmonella Typhi and Shigella species is described in this paper. This study should aid the development and licensing of new glycoconjugate vaccines aimed at the prevention of enteric diseases.
Introduction. Identification of pharmacogenetic effects on antiretroviral therapy (ART) has become an important milestone to reach in the advancement of personalised treatment for HIV-positive patients. The therapy schemes are accompanied by multiple side effects. Therapy effectiveness and adverse reactions can be dictated by individual genetic predisposition factors, which should be taken into account for an optimal prescription. Some genetic markers (HLA-B*57:01 and UGT1A1*28), were already proven to improve discontinuation rates, and efforts are allocated to expand the range of clinically-relevant genetic tests.Objective. In this review, an updated summary of genetic polymorphisms and their effects defining patients’ tolerability to ART is presented. The aim of this research is to assess single nucleotide polymorphisms (SNPs) present in the genes that encode proteins involved in ART metabolism and transport. This review will be used to develop a PCR-based testing methodology for the detection and confirmation of risk alleles in the Caucasian population.Materials and methods. Data from 46 original research papers and reviews was analysed. Allele frequencies of the most relevant polymorphisms were checked against the data for European population.Results. As an outcome of this review, a few most promising SNPs were selected for future research. Firstly, ABCC4 rs1751034 and rs3742106 and ABCC10 rs9349256 and rs2125739 were associated with an increased risk of renal impairment, higher plasma concentration, and toxicity when treated with tenofovir. Parallel analysis of ABCC4 and ABCC10 SNP effects on renal impairment together with CYP24A1 rs2248359 that was recently reported as a potential renal toxicity marker might be more informative. Secondly, CYP2B6 rs3745274 that was associated with an increased efavirenz plasma concentration, and increased risk of liver and CNS toxicity should be evaluated. SNPs in CYP2B6, CYP2A6 (rs28399433), and CYP3A4 (rs4646437) should be evaluated in parallel since possession of all three variants might put patients at a much higher risk.Conclusion. Identified alleles could become new markers used in drug prescription protocols if significant effect in Caucasian population will be found. The most relevant SNPs should be tested in in supporting future studies to evaluate the significance for patients with HIV in Russia.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.