Blood levels of TT virus following immune stimulation with influenza or hepatitis B vaccine

Torque Teno virus (TTV) has been demonstrated to be present persistently in the blood of healthy individuals without evidence that it causes any disease process. The levels of TTV vary in patients co-infected with other viruses and there has been considerable speculation as to whether TTV contributes to pathogenesis by other viruses or if the varying levels might be related to immune activation in the host. In the present study, the load of TTV was examined in plasma and peripheral blood mononuclear cells (PBMCs) following immunization of subjects with either influenza (a recall antigen) or hepatitis B virus (HBV) (a new antigenic exposure). The results overall did not indicate a significant change in TTV titers over a 90 day observation period; however, when TTV genogroup was taken into consideration there was an increase in viral load in plasma at some time points for subjects persistently infected with genogroup 3. While this was observed in both influenza and HBV immunized subjects, the effect was more profound in HBV vaccination. Thus, it appears that exposure to a new antigen rather than a recall antigen may stimulate TTV replication more effectively. The data further suggest that investigating the interactions between TTV and its host might require to examine specifically each TTV genogroup separately in order to determine if certain TTV types have any role in disease pathogenesis.     

Dominance,plasma testosterone levels,and testis size in house mice artificially selected for high activity levels

Male house mice (Mus domesticus) from four replicate lines selectively bred for high voluntary wheel-running behavior were compared with four random-bred control lines with respect to dominance, testis size, and plasma testosterone level. Behavior was measured with a tube apparatus in which focal mice encountered a standard opponent from an inbred strain, and positions of mice were scored over a 10-min period; the test was replicated the following day. Blood samples were taken from undisturbed mice 1 week prior to testing (baseline condition) and immediately after the first tube test; plasma testosterone was measured by enzyme immunoassay with chromatography. As compared with control lines, mice from selected lines tended to be smaller in body mass, to have larger testes, and were significantly less likely to advance towards their opponent during the second tube-test encounter. However, no significant differences in either baseline or post-encounter testosterone levels were detected. Significant differences in body mass, relative testis size, position during the first tube-test encounter, and baseline testosterone were found among the replicate lines within linetype, which indicates founder effects, random genetic drift, unique mutations, and/or multiple responses to selection. At the level of individual variation (residuals from nested analysis of covariance models), an inverse relationship between baseline testosterone and advancing in the tube test was observed, and the relationship was stronger during the second test day. This unexpected result may reflect an alternate coping strategy.     

Decrease in plasma noradrenaline levels following long-term treatment with prindolol in patients with essential hypertension

Summary 15 patients (4 females, 11 males, 21 to 55-year old) with mild to moderate essential hypertension (EH) were treated with placebo for two weeks and thereafter with increasing doses of prindolol (15 to 38 mg/day in the mean) and kept on a mean maintenance dosage of 32 mg/day for an average of 16 weeks in all. Blood pressure (BP), heart rate und plasma noradrenaline (PNA) concentrations were measured under standardized conditions (supine, standing, walking) at the end of two weeks on placebo and after the experimental treatment period. The results were compared to those of a group of 15 normotensive untreated control subjects (NS): after an average of 16 weeks on prindolol BP fell from 163/113 mm Hg to 129/91 mm Hg in the mean. PNA levels in EH before prindolol were significantly higher than in NS (supine: 272±22.0 ng/l (mean±SEM) vs. 135±15.1 ng/l, standing: 448±31.9 ng/l vs. 359±18.4 ng/l, walking: 388±22.5 ng/l vs. 234±22.1 ng/l). In EH chronic administration of prindolol led to a significant decrease in PNA concentrations under all the three test conditions to levels which did not differ significantly any more from those derived from NS. The adrenergic response to upright posture reflected in the percentage increase in PNA was significantly less in EH before prindolol when compared to the percentage increase in NS. On prindolol the adrenergic response was not abolished, yet it tended to approach the values found in NS. Before prindolol under resting conditions diastolic BP correlated closely with the corresponding PNA levels (p<0.01,r=0.66,n=15). This correlation could not be reestablished after prindolol treatment. The decrease in PNA after long-term treatment with prindolol was not correlated to the fall in blood pressure. The decrease in PNA indicates a lower activity of the sympathetic nervous system which may contribute to the antihypertensive effect of prindolol.     

海南汉族人群九个纤维蛋白原基因多态性及其与血浆纤维蛋白原水平的关系

目的 调查海南汉族健康人群αTaqⅠ和βBclⅠ、HinfⅠA／C、448G／A、βBsmA ⅠG／C、＋1689T／G、-148C／T、-249C／T、-455G／A多态性的等位基因频率及其与血浆纤维蛋白原（fibrinogen，Fg）水平的关系。方法 用比浊法测定238名健康个体的血浆Fg浓度，用PCR-限制性片段长度多态性方法及测序法分析多态性基因型，并用协方差分析比较9个位点的基因型与血浆Fg水平的关系。结果 海南汉族人群αTaqⅠ、βBclⅠ、HinfⅠA／C、C448、βBsmAⅠG／C、＋1689T／G、-148C／T、-249C／T、-455G／A稀有位点的等位基因频率分别为0．445、0．239、0．134、0．235、0．273、0．241、0．265、0．441、0．254，9个位点之间存在连锁不平衡；在总人群中，-455GA和AA基因型、-148CT和TT基因型、αTaqⅠT1T1基因型组的血浆Fg水平比野生型组高（P值均〈0．01）；在男性人群中，-455GA和AA基因型、-148CT和TT基因型、αTaqⅠT1T1、αTaqⅠT1T2基因型组的血浆Fg水平比野生型组高（P值均〈0．01）。在女性人群中，携带稀有位点A^-455、T^-148、αTaⅠT1的基因型组与野生型组之间的血浆赡水平差异无统计学意义。结论 在9个多态性位点之间存在连锁不平衡；A^-455、T^-148、αTaqⅠT1位点与血浆Fg水平增高关联，β-Fg-455G／A、-148C／T及α-TaqⅠ多态性与男性血浆Fg水平关联。     

Correlation between viral RNA levels but not immune responses in plasma and tissues of macaques with long-standing SIVmac251 infection

Plasma virus in human immunodeficiency virus type 1/simian immunodeficiency virus (HIV-1/SIV) infection most likely results from the combination of viruses produced in different tissues. As immunological pressure may be higher in effector sites than secondary lymphoid tissues, we investigated quantitative and qualitative changes in viral RNA in blood and tissues of 10 Mamu-A*01-positive SIV-infected macaques in parallel with the frequency of CD8+ T cells recognizing the dominant Gag181-189 CM9 epitope. The plasma virus level in these macaques directly correlated with the viral RNA levels in lymph nodes, spleen, lungs, colon, and jejunum. In contrast, the frequency of the Gag181-189 CM9 tetramer did not correlate with SIV RNA levels in any compartment. We investigated the presence of viral immune escape in RNA from several tissues. The complete substitution of wild-type genotype with viral immune-escape variant within the Gag181-189 CM9 epitope was associated with low tetramer response in all tissues and blood of two macaques. In one macaque, the replacement of wild type with an immune-escape mutant was asynchronous. While the mutant virus was prevalent in blood and effector tissues (lungs, jejunum, and colon), secondary lymphoid organs such as spleen and lymph nodes still retained 80% and 40%, respectively, of the wild-type virus. These results may imply that there are differences in the immunological pressure exerted by cytotoxic T lymphocytes (CTLs) in tissue compartments of SIVmac251-infected macaques.     

妊娠糖尿病孕妇血浆抵抗素水平及其与胰岛素和血糖关系的研究

目的探讨妊娠期糖尿病(GDM)孕妇血浆抵抗素水平及其与胰岛素和血糖的关系。方法采用竞争性酶联免疫吸附法(ELI SA)检测25例GDM组孕妇和30例正常孕妇空腹血浆抵抗素水平;采用葡萄糖氧化酶法测定两组孕妇空腹血糖水平;采用电化学发光法测定两组孕妇的空腹血浆胰岛素水平。结果(1)GDM组孕妇空腹血浆抵抗素水平为(15.32±4.26)μg/L,正常妊娠组孕妇为(11.08±1.52)μg/L两组比较,差异有极显著性(P<0.01);(2)GDM组孕妇空腹血浆胰岛素,血糖水平分别为(13.18±3.25)m IU/L,(9.13±1.34)mmol/L正常妊娠组孕妇分别为(9.10±3.41)m IU/L,(4.72±1.05)mmol/L。两组比较差异有极显著性(P<0.01);(3)GDM组孕妇血浆抵抗素水平与胰岛素、血糖水平呈明显的正相关关系,相关系数(r)分别为0.812,0.573;正常妊娠组孕妇则无相关性。结论GDM孕妇血浆抵抗素水平升高,其抵抗素水平的高低与空腹血浆胰岛素及血糖水平相关。     

Enhanced mucosal and systemic immune responses following intravaginal immunization with human papillomavirus 16 L1 virus-like particle vaccine in thermosensitive mucoadhesive delivery systems

To develop more potent and convenient mucosal human papillomavirus (HPV) vaccines, we tested the effect of thermosensitive mucoadhesive vaginal vaccine delivery systems on the local and systemic antibody responses to HPV 16 L1 virus-like particles (VLP). HPV 16 L1 VLP expressed from recombinant baculovirus-infected Sf21 insect cells were delivered in phosphate-buffered saline (PBS) or thermosensitive mucoadhesive delivery systems, composed of poloxamers (Pol) and varying amounts of polyethylene oxide (PEO). Pol/PEO-based vaginal vaccine delivery systems existed in liquid form at room temperature, but gelled at 37 degrees C. The mucoadhesiveness of Pol/PEO-based delivery systems increased with PEO, but the formulations with PEO higher than 1.0% were too viscous to be administered into the vagina. Vaccine vehicles affected the vaginal and salivary immune responses to HPV 16 L1 VLP intravaginally administered into mice. At 42 days after the first intravaginal immunization of HPV 16 L1 VLP with cholera toxin, vaginal and salivary IgA titers were the highest in the group given in Pol/PEO 1.0% vehicle followed by Pol/PEO 0.4% and PBS vehicles. Intravaginal coadministration of HPV 16 L1 VLP and cholera toxin in Pol/PEO 1.0% showed 31- and 39-fold higher titers compared to the PBS-based HPV 16 L1 VLP groups administered by intravaginal and intramuscular routes, respectively. Following intravaginal administration, Pol/PEO 1.0%, but not Pol/PEO 0.4%, showed significantly higher HPV 16 L1 VLP-specific serum IgG titers as compared to the PBS vehicle. Our results indicate that the use of in situ-gelling vaginal vaccine delivery systems with increased mucoadhesiveness would be beneficial for more effective induction of mucosal and systemic immune responses to intravaginally administered HPV 16 L1 VLP vaccines.     

Constitutive expression of high levels of soluble mouse CD4 in transgenic mice does not interfere with their immune function

Interactions of CD4 with the major histocompatibility complex (MHC) class II molecules are crucial during thymic development and subsequently for the function of single-positive CD4⁺CD8^? T lymphocytes. Here, we have investigated the potential effects of soluble CD4 (sCD4) on the immune system. We generated two different transgenic mouse lines, which constitutively expressed either ?100 μg/ml of monovalent or ?20 μg/ml f decavalent mouse sCD4 molecules in their sera. Analysis of these mice revealed no differences compared to control littermates, e.g. the single-positive CD4⁺ cells developed normally and these cells responded to allogeneic and anti-CD3 antibody stimuli like the cells from control mice. Furthermore, the T helper cell function for antibody responses in vivo were not affected. Our data provide evidence that, in mouse, the CD4-MHC class II-interaction has very low affinity. Since sCD4 is considered to be a therapeutical agent for human immunodeficiency virus infection, these findings are not only of basic, but also of clinical interest.     

Material-dependent levels of heat-shock protein 70 (hsp70) in human plasma following contact of blood with artificial surfaces

Recently, it has been shown that heat-shock protein 70 (hsp70) functions in a dual role as a chaperone and a cytokine. However, no information is available on the occurrence of hsp70 in the extracellular milieu or on its ability to modulate cellular immune response. This study shows a material-dependent increase of hsp70 levels in plasma following contact of fresh heparinized whole human blood with three different biomaterials (PVC, heparin-coated PVC, Silicone). We report a previously unknown behavior of hsp70 to act as a plasma-adsorption protein. Further, high binding capacities for hsp70 to artificial surfaces (measured by Western blotting) and elevated hsp70 levels in plasma (measured by EIA) following contact with blood correspond with a reduced hemocompatibility. The degree of surface-induced activation of blood was determined by analysis of markers for coagulation, inflammation and complement activation. These findings indicate that the selective adsorption of hsp70 on artificial surfaces and the increased hsp70 levels in plasma may be important in directing host inflammatory and immune responses. We suggest that the levels of hsp70 in human plasma may represent a new prognostic factor or a diagnostic biomarker in hemostasis research.     

肾综合征出血热纯化疫苗候选毒株在Vero细胞上的适应传代及其免疫原性研究

目的 将肾综合征出血热纯化疫苗候选毒株适应于Vero细胞，并对其抗原性和免疫原性进行研究。方法 将汉滩病毒H8207株和汉城病毒Y86013株在Vero细胞上进行连续终末稀释传代，采用间接免疫荧光法、酶联免疫吸附试验和空斑减少中和试验，研究传代后毒株的繁殖特性、病毒滴度、抗原量及免疫原性。结果 经过5次终末稀释传代，两株病毒在Vero细胞上均显示出良好的适应性，从第六代开始病毒滴度稳定在7．0Lg TCID50/m1以上，第八代两毒株抗原量均已达到1：64，H8207株抗原量继续升高，最高时达1：256。用两株病毒不同培养代次上清液制备的单价原液灭活疫苗免疫家兔二针，免疫血清对同型毒株的中和效价均达到1：10。结论 两株病毒已适应于Vero细胞，且具有病毒滴度高和免疫原性良好的特性，适合用作Vero细胞肾综合征出血热灭活纯化疫苗的候选毒株。     

Glycated plasma proteins in experimentally induced acute toxic renal failure by dichromate injection: evidence for loss with urine and decreased plasma levels.

In the rat, a single subcutaneous injection of sodium dichromate (20 mg/kg) causes acute renal injury and significant polyuria, proteinuria, and glycosuria (peaking 2–3 days after treatment, and returning to normal by day 5) without any changes in the plasma levels of protein, glucose, and glycated haemoglobin. Surprisingly, the percentage levels of glycated plasma total proteins and albumin (assayed by boronate affinity chromatography) transiently and significantly decrease during recovery from proteinuria (days 4 and 10 after treatment) and were found in the normal range of values by day 18. These changes are concomitant with a significant increase in the percentage level of glycated albumin in urine. Constancy of total plasma protein and the temporal pattern of levels of glycation suggest that changes in the percentage values of glycated proteins are secondary to a transient selective loss of glycated plasma proteins in urine.     

Normotensive normoxic men undergoing water diuresis fail to respond to stimulation of their peripheral arterial chemoreceptors by almitrine with an increase in plasma concentrations of atrial natriuretic factor

Summary The purpose of this study was to investigate the possible participation of atrial natriuretic factor (ANF) in the natriuretic and diuretic response occurring after stimulation of the peripheral arterial chemoreceptors by almitrine bismesylate in normoxic humans. The experiments were performed in 14 healthy male volunteers undergoing water diuresis. Each subject participated in two experiments. In one of them they ingested 100-mg almitrine at 12 p.m. The other study served as a control. Surprisingly, our subjects responded to almitrine with an elevation of urine flow only, whereas sodium excretion remained almost unchanged over the whole period of the experiments. As regards ANF plasma concentrations, no statistically significant differences between the control and the almitrine group could be observed. Moreover, no direct connection between ANF plasma concentrations and renal volume excretion was detectable. We concluded that a specific stimulation of peripheral arterial chemoreceptors by almitrine in humans undergoing water diuresis did not seem to raise ANF plasma concentrations as is the case at high altitude. Therefore we would suggest that there exists no specific reflex influence of these receptors on ANF release.     

High plasma levels of apo(a) fragments in Caucasians and African-Americans with end-stage renal disease: implications for plasma Lp(a) assay

Apolipoprotein(a) [apo(a)] is a plasma glycoprotein that is highly polymorphic in size due to differences in the number of a tandemly arrayed cysteine-rich repeat called kringle (K)4 at its N-terminus. Most plasma apo(a) is covalently attached to apolipoprotein B-100 and circulates as part of lipoprotein(a) [Lp(a)]. A fraction of apo(a) circulates free of lipoproteins. Almost all of the free apo(a) consists of fragments containing variable numbers of K4 repeats derived from the N-terminal region. Previously we provided evidence suggesting that the apo(a) fragments present in human plasma are the source of the apo(a) fragments in human urine. If this were the case, it would be expected that plasma levels of fragments would be higher in subjects with end-stage renal disease (ESRD). In this paper we quantified the levels of apo(a) fragments and plasma Lp(a) in 26 Caucasian and 26 African-American subjects with ESRD and 52 healthy subjects matched for race, sex and the size of the apo(a) isoforms. The plasma levels of apo(a) fragments and Lp(a) were both higher in the ESRD subjects. In addition, the ratio of apo (a) fragments to total immunodetectable apo(a) was increased in ESRD. To determine how much the increase in the apo(a) fragments contributed to the increase in plasma Lp(a) in ESRD, the plasma Lp(a) levels were measured employing two different anti-apo(a) enzyme-linked immunoabsorption assays (ELISA). One assay detected both free and bound apo(a), whereas the other assay detected only bound apo(a). Although the plasma levels of apo(a) in the ESRD subjects tended to be higher using the assay that detected both fragments and full-length apo(a), the increase was modest. Thus, although a greater proportion of the apo(a) in ESRD plasma circulates as fragments, most of the elevation in plasma levels of Lp(a) associated with renal insufficiency is due to an increase in intact Lp(a).     

Evidence for a selected humoral immune response encoded by VH4 family genes in the synovial membrane of a patient with rheumatoid arthritis (RA)

The analysis of rearranged antibody-encoding genes from B cell foci in rheumatoid synovial tissue has characterized these cells as highly mutated memory B cells with a high proportion of members of the V_H4 family. In order to characterize further the V_H4 response in one patient, B cell-rich areas from different sections of synovial membrane (SM) were identified by CD20 staining, isolated by microdissection and pooled, in order to analyse highly enriched B cells without selection by in vitro culture procedures. From DNA of about 5 × 10³ B cells rearranged V_H genes were amplified by polymerase chain reaction (PCR) and cloned. Sequencing of 11 clones containing rearranged V_H4 gene products revealed that seven were potentially functional, and all were mutated with 84–96% homology to known germ-line (gl) genes and V_H4 gl genes amplified from the patient’s genomic DNA. Analysis of the complementarity determining region (CDR) 3 revealed that two products represented members of one B cell clone which differed by five nucleotide changes. Three of the five mutations encoded amino acid replacements in CDRs indicating antigen-driven expansion of one specific clone. Additional analyses of 25 members of three B cell clones from isolated aggregates showing intraclonal diversity in one of three clones provided further evidence that antigen selection takes place in the SM. Overall, the pattern of mutations and the replacement to silent (R:S) ratios were diverse, with six products indicating antigen selection by their high R:S ratios in CDRs. Although DNA analysis does not allow a characterization of antibody specificities, we can conclude from our analysis of antibody-encoding genes that selection by antigen and expansion of specific clones occur in the SM against the background of polyclonal activation.     

An engineered Plasmodium falciparum C-terminal 19-kilodalton merozoite surface protein 1 vaccine candidate induces high levels of interferon-gamma production associated with cellular immune responses to specific peptide sequences in Gambian adults naturally exposed to malaria

The 19-kDa C-terminal region of merozoite surface protein 1 (MSP1(19)), a major blood stage malaria vaccine candidate, is the target of cellular and humoral immune responses in humans naturally infected with Plasmodium falciparum. We have previously described engineered variants of this protein, designed to be better vaccine candidates, but the human immune response to these proteins has not been characterized fully. Here we have investigated the antigenicity of one such variant compared to wild-type MSP1(19)-derived protein and peptides. Gambian adults produced both high T helper type 1 (Th1) [interferon (IFN)-γ] and Th0/Th2 [interleukin (IL)-13 and sCD30] responses to the wild-type MSP1(19) and the modified protein as wells as to peptides derived from both forms. Response to the modified MSP1(19) (with three amino acid substitutions: Glu27Tyr, Leu31Arg and Glu43Leu) relative to the wild-type, included higher IFN-γ production. Interestingly, some peptides evoked different patterns of cytokine responses. Modified peptides induced higher IL-13 production than the wild-type, while the conserved peptides P16 and P19 induced the highest IFN-γ and IL-13 and/or sCD30 release, respectively. We identified P16 as the immunodominant peptide that was recognized by cells from 63% of the study population, and not restricted to any particular human leucocyte antigen D-related (HLA-DR) type. These findings provide new and very useful information for future vaccine development and formulation as well as potential Th1/Th2 immunmodulation using either wild-type or modified protein in combination with their peptides.     

Apolipoproteins B and E, and angiotensin I-converting enzyme (ACE) genetic polymorphisms in Italian women with coronary artery disease (CAD) and their relationships with plasma lipid and apolipoprotein levels

The Xba I, Eco RI and the signal peptide insertion/deletion ( I/D ) polymorphic sites of APOB gene, the Cfo I polymorphic site of apolipoprotein E gene (APOE), and the insertion/deletion polymorphism of angiotensin I-converting enzyme (ACE) gene were studied using polymerase chain reaction (PCR) in 55 postmenopausal women with coronary artery disease (CAD) and in 119 control women of equivalent age. Patients and controls were recruited from the population of Rome, considered representative of Central and Southern Italy. There were no significant differences in allele frequencies between the two groups, though APOB X-, R- and I, APOE*3 , and ACE D alleles were slightly more frequent in the cases than in the controls. The patients did not differ from the controls for plasma total cholesterol (TC), HDL-cholesterol, LDL-cholesterol, and apoAI values, while they presented significantly higher levels of triglycerides and apoB, and lower apoE levels. TC, apoE, and apoB quantitative values, adjusted for age, varied significantly among APOB Xba I and APOE genotypes. APOB X-X-genotype was associated in patients with a significantly lower mean TC concentration than the other two genotypes pooled together. APOE 3–2 genotype in the controls had significantly lower TC levels with respect to the other two pooled genotypic classes and higher apoE levels compared to 3–3 and 4–3 genotypes. In the patients, 3–2 genotype had significantly lower apoB levels than the pooled 3–3 and 4–3 class. We conclude that in the Italian women the DNA polymorphisms studied in this work do not seem to be important risk factors for CAD occurrence; that apoE quantitation could be another useful parameter to identify subjects at risk of CAD; and that APOB X -and APOE*2 are the alleles that most influence the interindividual plasma lipid variation among CAD female patients.     

Comparison of quantitative cDNA-PCR with the branched DNA hybridization assay for monitoring plasma hepatitis C virus RNA levels in haemophilia patients participating in a controlled interferon trial

The branched DNA (bDNA) assay was compared with a semi-quantitative cDNA-polymerase chain reaction (cDNA-PCR) assay for monitoring HCV RNA levels in plasma in 17 haemophilia patients participating in a controlled a-interferon trial. Good correlation between the HCV RNA levels as detected by the two assays was observed, with a correlation co-efficient of 0.83 (P < 0.0001) and 0.90 (P < 0.0001) at week 0 and 24, respectively. Hepatitis C virus RNA (HCV RNA) levels could be assessed with the bDNA assay in 14/17 (82 percent) HCV cDNA-PCR positive pre-treatment samples. The bDNA assay apparently failed to detect low viral titres. (riterferon treated patients (n = 11) showed either a complete response, being a large reduction in HCV RNA level to below the detection limit of the HCV cDNA-PCR assay (6/11) or no significant reduction in HCV RNA level (5/11). A “partial” virological response was not observed. The changes in HCV RNA plasma levels in non-responders during interferon (IFN) treatment were similar to the (small) natural fluctuations in viral load observed in controls (untreated patients). Although the bDNA assay was not as sensitive as cDNA-PCR, given its user friendliness and quantitative results, it is concluded that it is a useful test for monitoring HCV RNA levels in patients treated with interferon. However, patients who are non-reactive in the bDNA assay have to be retested by cDNA-PCR because low viral titres are not detected by the bDNA assay. © 1994 Wiley-Liss, Inc.     

VP7 and VP4 genotypes of rotaviruses cocirculating in Iran, 2015 to 2017: Comparison with cogent sequences of Rotarix and RotaTeq vaccine strains before their use for universal mass vaccination

The present study was conducted to analyze the genotypic diversity of circulating species A rotavirus (RVA) strains in Iran and also to investigate comparative analysis between the genotypes of VP4 and VP7 of cocirculating RVA and vaccine strains before the vaccine is introduced in the national immunization program. The G3-lineage I was found in this study as the most common G genotype which was followed by G9-lineage III, G1-lineages I, II, G12-lineage III, G2-lineage IV, and G4-lineage I. Also, P[8]-lineages III, IV was found as the predominant P genotype which was followed by P[4]-lineage V, and P[6]-lineage I. Overally, G3P[8] was determined as the most common combination. Moreover, the analysis of the VP7 antigenic epitopes showed that several amino acid differences existed between circulating Iranian and the vaccine strains. The comparison of genotype G1 of Iranian and vaccine strains (RotaTeq and Rotarix), and genotypes G2, G3, and G4 of Iranian and RotaTeq vaccine strains revealed three to five amino acids differences on the VP7 antigenic epitopes. Furthermore, analyzing of the VP8* epitopes of Iranian P[8] strains indicated that they contained up to 11 and 14 amino acid differences with Rotarix and RotaTeq, respectively. Based on different patterns of amino acid substitutions in circulating and vaccine strains, the emergence of antibody escaping mutants and potentially the decrease of immune protection might ensue in vaccinated children. However, considering the broad cross-protective activity of RVA vaccines, their efficacy should be monitored after the introduction in Iran.