Search citation statements
Paper Sections
Citation Types
Year Published
Publication Types
Relationship
Authors
Journals
Background. Toll-like receptors (TLR) play a key role in the innate immune system, as they are the fi rst to recognize a foreign agent and initiate the human body defense mechanism. At present, the role of toll-like receptors in predicting infectious diseases requires further investigation.Objectives. To study TLR3 (Phe412Leu), TLR9 (A2848G) and TLR9 (T1237C) polymorphisms in healthy individuals and chickenpox patientsMethods. An observational cohort study involved 201 conscripted soldiers of Caucasian race, aged between 18 and 24, who was born in) and served in Zabaykalsky Krai. All of them agreed to participate voluntarily. The main group was represented by 105 males who received treatment at a military hospital with a diagnosis of chickenpox in 2019. The control group consisted of 96 healthy conscripts. The study was carried out on the basis of Chita State Academy of Medicine, Russia, and included a physical examination, anthropometry, determination of SNP genes by PCR. Amplifi cation of TLR3 and TLR9 gene fragments was carried out by means of thermocycler BIS-М111. IBM SPSS Statistics 25.0 (International Business Machines Corporation, License No. Z125-3301-14, USA) was used for statistical processing of the results.Results. A total of 354 people were screened, 87 of them did not meet the inclusion criteria and 19 refused to participate in the study. 134 males were excluded in the process, 47 of which appeared to have an exacerbation of chronic diseases, 21 were not of Caucasian race, 64 were not born in Zabaykalsky Krai, and 2 did not meet the age criteria. Totally, the study included 201 conscripted soldiers. The study groups were established as follows: chickenpox patients (n = 105) and healthy individuals (controls, n = 96). The -412Leu allele was 1.8 times less frequent in the chickenpox group, with a frequency of 0.138, compared with 0.250 in healthy controls (Ȥ 2 = 8.11; p = 0.004). In the main group, allele -412Phe prevailed with a frequency of 0.862, whereas in the control group its frequency was 0.750 (χ2 = 8.11; p = 0.004). In patients group, the genoype Phe412Phe prevailed (75.2%), the genotype Leu412Leu was less common — 2.9% (Ȥ 2 = 7.09; p = 0.03). In the group of healthy individuals, the distribution of genotypes was as follows: Phe412Phe — 60.4%, Phe412Leu — 30.2%, Leu412Leu — 9.4% (Ȥ 2 = 7.09; ɪ = 0.03). Carriers of allele -412Phe (OR = 2.08 [CI95%: 1.25–3.47]) and genotype Phe412Phe (OR = 2.08 [CI95%: 1.14–3.80]) are more likely to develop chickenpox. The probability of developing the disease for persons having the major allele A of the genotype TLR9 (Ⱥ2848G) is 0.29 [CI95%: 0.19– 0.43], for individuals with the mutant allele G of the genotype TLR9 (Ⱥ2848G) — 3.50 [CI95%: 2.32–5.29]. The prevalence of TLR9 (T1237C) in the main group was not signifi cantly different from that in the control group (p > 0.05). The probability of developing the disease for persons having the major allele A is 0.29 [95% CI 0.19–0.43], for carriers of the mutant allele G — 3.50 [95% CI 2.32-5.29]. When analyzing SNP TLR9 (A2848G), it was found that allele G prevailed with a frequency of 0.614, and allele A — with a frequency of 0.386, which is 1.9 times less than in the control group (Ȥ 2 = 36.67; p < 0.001). In patients group, homozygotes AA were found in 9.5% of cases, heterozygotes AG — in 58.1%, the rest cases were homozygous variants GG (Ȥ 2 = 40.11; p < 0.001). In the control group, all possible genotypes with a predominance of the heterozygous genotype AG were identifi ed and comprised 47.9%. When assessing the relative risk of gene variation associations connected with the development of chickenpox, we found that the polymorphism of genes TLR9 (A2848G) AG/GG increases the risk of the development of disease caused by varicella virus in the studied category by 3.4 times, and the polymorphism TLR3 (Phe412Leu) Phe/ Phe — by 1.42 times. The ROC analysis was carried out, the area under curve was 0.77 (95% CI0.70–0.83); p < 0.001; specifi city — 0.62; sensitivity — 0.8. The developed model, being a relatively good identifi er, has satisfactory properties as a discriminator.Conclusion. Our study suggests that allele -412Phe and homozygous variant Phe412Phe of gene TLR3 (Phe412Leu), as well as allele G and homozygous variant GG of gene TLR9 (A2848G) predispose to chickenpox development. Meanwhile, the allele -412Leu of gene TLR3 (Phe412Leu), allele A, and homozygous variant AA of gene TLR9 (A2848G) reduce the probability of chickenpox development.
Background. Toll-like receptors (TLR) play a key role in the innate immune system, as they are the fi rst to recognize a foreign agent and initiate the human body defense mechanism. At present, the role of toll-like receptors in predicting infectious diseases requires further investigation.Objectives. To study TLR3 (Phe412Leu), TLR9 (A2848G) and TLR9 (T1237C) polymorphisms in healthy individuals and chickenpox patientsMethods. An observational cohort study involved 201 conscripted soldiers of Caucasian race, aged between 18 and 24, who was born in) and served in Zabaykalsky Krai. All of them agreed to participate voluntarily. The main group was represented by 105 males who received treatment at a military hospital with a diagnosis of chickenpox in 2019. The control group consisted of 96 healthy conscripts. The study was carried out on the basis of Chita State Academy of Medicine, Russia, and included a physical examination, anthropometry, determination of SNP genes by PCR. Amplifi cation of TLR3 and TLR9 gene fragments was carried out by means of thermocycler BIS-М111. IBM SPSS Statistics 25.0 (International Business Machines Corporation, License No. Z125-3301-14, USA) was used for statistical processing of the results.Results. A total of 354 people were screened, 87 of them did not meet the inclusion criteria and 19 refused to participate in the study. 134 males were excluded in the process, 47 of which appeared to have an exacerbation of chronic diseases, 21 were not of Caucasian race, 64 were not born in Zabaykalsky Krai, and 2 did not meet the age criteria. Totally, the study included 201 conscripted soldiers. The study groups were established as follows: chickenpox patients (n = 105) and healthy individuals (controls, n = 96). The -412Leu allele was 1.8 times less frequent in the chickenpox group, with a frequency of 0.138, compared with 0.250 in healthy controls (Ȥ 2 = 8.11; p = 0.004). In the main group, allele -412Phe prevailed with a frequency of 0.862, whereas in the control group its frequency was 0.750 (χ2 = 8.11; p = 0.004). In patients group, the genoype Phe412Phe prevailed (75.2%), the genotype Leu412Leu was less common — 2.9% (Ȥ 2 = 7.09; p = 0.03). In the group of healthy individuals, the distribution of genotypes was as follows: Phe412Phe — 60.4%, Phe412Leu — 30.2%, Leu412Leu — 9.4% (Ȥ 2 = 7.09; ɪ = 0.03). Carriers of allele -412Phe (OR = 2.08 [CI95%: 1.25–3.47]) and genotype Phe412Phe (OR = 2.08 [CI95%: 1.14–3.80]) are more likely to develop chickenpox. The probability of developing the disease for persons having the major allele A of the genotype TLR9 (Ⱥ2848G) is 0.29 [CI95%: 0.19– 0.43], for individuals with the mutant allele G of the genotype TLR9 (Ⱥ2848G) — 3.50 [CI95%: 2.32–5.29]. The prevalence of TLR9 (T1237C) in the main group was not signifi cantly different from that in the control group (p > 0.05). The probability of developing the disease for persons having the major allele A is 0.29 [95% CI 0.19–0.43], for carriers of the mutant allele G — 3.50 [95% CI 2.32-5.29]. When analyzing SNP TLR9 (A2848G), it was found that allele G prevailed with a frequency of 0.614, and allele A — with a frequency of 0.386, which is 1.9 times less than in the control group (Ȥ 2 = 36.67; p < 0.001). In patients group, homozygotes AA were found in 9.5% of cases, heterozygotes AG — in 58.1%, the rest cases were homozygous variants GG (Ȥ 2 = 40.11; p < 0.001). In the control group, all possible genotypes with a predominance of the heterozygous genotype AG were identifi ed and comprised 47.9%. When assessing the relative risk of gene variation associations connected with the development of chickenpox, we found that the polymorphism of genes TLR9 (A2848G) AG/GG increases the risk of the development of disease caused by varicella virus in the studied category by 3.4 times, and the polymorphism TLR3 (Phe412Leu) Phe/ Phe — by 1.42 times. The ROC analysis was carried out, the area under curve was 0.77 (95% CI0.70–0.83); p < 0.001; specifi city — 0.62; sensitivity — 0.8. The developed model, being a relatively good identifi er, has satisfactory properties as a discriminator.Conclusion. Our study suggests that allele -412Phe and homozygous variant Phe412Phe of gene TLR3 (Phe412Leu), as well as allele G and homozygous variant GG of gene TLR9 (A2848G) predispose to chickenpox development. Meanwhile, the allele -412Leu of gene TLR3 (Phe412Leu), allele A, and homozygous variant AA of gene TLR9 (A2848G) reduce the probability of chickenpox development.
One of the important directions for increasing the immunogenic properties of vaccine strains against highly dangerous infections is the search for adjuvants that not only stimulate the immunological effectiveness of vaccination, but can also provide a metabolic correction of the vaccination process. Organoselenium compounds have immunotropic properties and an antioxidant effect, and therefore, the study of the effect of the organoselenium compound 2,6-dipyridinium-9-selenabicyclo[3.3.1]nonane dibromide (974zh) on the activity of the TLR2 and TLR4 gene expression by macroorganism cells of experimental animals immunized with Yersinia pestis EV NIIEG vaccine strain, is a current area of research.The aim of the work. To assess the TLR2 and TLR4 gene expression by cells of the immune phagocyte system of experimental animals immunized with the Y. pestis EV vaccine strain against the background of immunomodulation with the organoselenium compound 974zh.Materials and methods. The study was carried out on 125 certified outbred white mice. Biological material (blood, spleen) was disinfected, and the spleen was homogenized. RNA isolation and reverse transcription were performed using commercial reagent kits. The expression level of the TLR2 and TLR4 genes was determined using real-time polymerase chain reaction with specific primers.Results. When assessing innate immunity using the example of blood and spleen cells of animal models, features of the TLR2 and TLR4 gene expression were revealed in response to the introduction of the Y. pestis EV vaccine strain against the background of immunomodulation with the 974zh. It was found that 974zh induces a statistically significant increase in TLR2 gene expression when co-administered with Y. pestis EV at a dose of both 104 CFU and 103 CFU.Conclusion. Y. pestis EV against the background of immunomodulation with 974zh, stimulates the expression of the TLR2 and TLR4 genes, which may indicate an increase in the immunogenic properties of the Y. pestis EV vaccine strain under the influence of this preparation.
One of the major public health challenges today is development of new vaccines and technologies to optimize the vaccination process. There is a growing scientific interest in vaccine adjuvants that enhance vaccine immunogenicity. At present, numerous studies are underway to develop COVID-19 vaccines, including inactivated and subunit vaccines which contain adjuvants for efficient induction of immune response and solid immunity. The aim of the study was to systematise literature related to the analysis of the structure, mechanisms of action and stimulating properties of vaccine adjuvants (synthetic oligodeoxynucleotides, virosomes, polyoxidonium, sovidone), as well as to summarise data on the effects of adjuvants used in SARS-CoV, MERS-CoV, and SARS-CoV-2 vaccine development studies. The paper analyses the prospects for enhancing the stimulating effect of the adjuvants when used in combination with compounds having a different mechanism of action. It also analyses the results of studies of adjuvanted vaccines against SARS-CoV and MERS-CoV, which may be useful when selecting adjuvants with optimal efficacy and safety profiles to be used in SARS-CoV-2 vaccines under development. It was concluded that understanding of the mechanisms of action of adjuvants that mediate their stimulating effect on the body’s immune system will contribute to safe and effective use of adjuvants to enhance the immunogenicity of both authorised and new vaccines.
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.
customersupport@researchsolutions.com
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
This site is protected by reCAPTCHA and the Google Privacy Policy and Terms of Service apply.
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.