Trichuris muris: antigen recognition and transfer of immunity in mice by IgA monoclonal antibodies

Mesenteric node lymphocytes from mice that had been infected with the nematode Trichuris muris, and then boosted with adult worm excretory-secretory antigens were fused with myeloma cells to produce a panel of 9 monoclonal antibodies (MoAbs). Five of the MoAbs were of the IgA isotype. The antigen recognition profiles of these MoAbs were studied using SDS-PAGE and immunoblotting; three major profile patterns were identified. Five MoAbs recognized a major band in the MW range 43-48 kD; all recognized a range of antigens. Three MoAbs were used to localize antigens in the bodies of adult worms. Granules within the anterior stichocytes were recognized strongly, as was material within the eggs and pseudocoelom. Two MoAbs stained the cuticle. Although the phosphorylcholine (PC) determinant was widely distributed within worm tissues none of the MoAbs tested recognized PC. Passive transfer of immunity was achieved using two of the IgA monoclonals; no immunity was transferred by the IgM and IgG MoAbs used. The limited recognition profiles of these IgA MoAbs, and the ability to stain stichocyte granules, suggest that their protective activity results from an interaction with ES antigens.     

MHC-restricted antibody responses to Trichuris muris excretory/secretory (E/S) antigen

Summary Two panels of H-2 recombinant mice were used in a detailed serological study to analyse the role of H-2-linked genes in the control of the antibody response to excretory/secretory (E/S) antigens of Trichuris muris. An apparent H-2 ^q ( 1-A ^q) restriction on the early development of high levels of IgGl antibody to E/S antigen was revealed by ELISA. No such restriction was demonstrated for the specific IgG2a response patterns. Recognition of two high molecular weight antigens (90–95 kDa, 105–110 kDa) by IgG antibodies was also shown to be almost exclusively H-2 ^q restricted and may be related at least in part to the high antibody levels seen for H-2 ^q strains of mice. Immune serum from resistant (B10.BR × B10.G) Fl hybrid mice ( H-2 ^qk) containing high levels of IgGl antibodies specific for T. muris E/S and IgG antibodies which recognized the 90–95 kDa and 105–110 kDa E/S antigens was effective in transferring protection to the non-responsive B10.BR mouse strain as seen on day 35 post-infection (p.i.). It is suggested that the IgG responses described for the generally very resistant H-2 ^q mouse strains may contribute to, but not be an absolute requirement for. protective immunity, antibody-mediated damage facilitating a subsequent cellular attack in certain strains of mice.     

Regulation of colonic epithelial cell turnover by IDO contributes to the innate susceptibility of SCID mice to Trichuris muris infection

Tryptophan catabolism via the kynurenine pathway is dependent on the enzyme Indoleamine 2,3-dioxygenase (IDO). Expression of IDO is upregulated in a number of inflammatory settings such as wounding and infection, and the resulting local tryptophan depletion may inhibit the replication of intracellular pathogens. Indo gene expression is upregulated in the gut during chronic infection with the mouse whipworm Trichuris muris. We demonstrate an increase in the rate of colonic epithelial cell turnover after inhibition of IDO in T. muris-infected SCID mice, leading to a significant expulsion of parasite burden. We identify the goblet cell as a novel source of IDO and present data revealing a new role for IDO in the regulation of epithelial cell turnover post-infectious challenge.     

The influence of protein deficiency on immunity to Heligmosomoides polygyrus (Nematoda) in mice

The influence of dietary protein on the efficiency with which mice could be immunized against infection with the nematode Heligomosomoides polygyrus was investigated. Immunization with irradiated larvae did not protect outbred mice fed synthetic diets containing 2% or 4% protein against a challenge infection, while animals fed a diet containing 8% protein were significantly resistant. In further experiments with high-responder NIH mice, protein malnutrition was again found to cause a significant depression in immunity. Immunization primed all mice for an intense production of antibody against larval worms in a challenge infection, and although a slightly higher titre of antibody was detected in the plasma of mice fed a 16% compared with a 2% protein diet it seemed unlikely that this was sufficient to account for the reduced resistance of the malnourished mice. The development of eosinophilia in the blood of immunized mice was significantly delayed in malnourished animals following challenge, and it is suggested that a reduction in the number of granulocytes attacking larval worms contributed to the low level of resistance observed in these animals. Protein malnutrition thus markedly suppresses the effectiveness of immunization of mice against an intestinal nematode, and it is suggested that this result may be of general significance with regard to the potential for widespread immunization of people against infections of this type.     

Comparative studies on immune responses to infection in susceptible B10.BR mice infected with different strains of the murine nematode parasite Trichuris muris

A comparison of immune responses to infection between groups of B10.BR mice infected with different strains of T. muris , S strain (isolated in Sobreda, Portugal), E strain (isolated in Edinburgh), and E-J strain (originally E strain, which has been maintained in our laboratory, Japan), was performed. In mice infected with E and E-J strains, most of the worms were expelled by day 32 after infection, though the expulsion was faster in E-J strain-infected mice. In contrast, no expulsion was observed in S strain-infected mice by day 32 and egg production occurred on day 32. IL-4 production occurred in concanavalin A (Con-A)-stimulated mesenteric lymph node cells (MLNC) from B10.BR mice infected with E and E-J strains, whereas no IL-4 production was observed in S strain-infected mice. IL-4 production did not occur in normal mice. In comparison with normal mice, high levels of IFN-γ production by Con A-stimulated MLNC were detected in mice infected with every strain of  T. muris . IFN-γ production in S strain-infected mice was greater, occurred earlier and was more persistent than in mice infected with E and E-J strains. IgG1 and IgG2a antibodies to T. muris excretory/secretory antigens were observed in B10.BR mice infected with every strain of T. muris . Antibody production showed similar kinetics. These differences in the expulsion kinetics and IL-4 production in B10.BR mice infected with S, E, and E-J strains suggest the involvement of IL-4 in protection against T. muris infection, and confirm the previous conclusion by Else et al . (1994).     

Zinc deficiency impairs T cell function in mice with primary infection of Heligmosomoides polygyrus (Nematoda)

This study was designed to determine whether severe zinc deficiency would prolong the course of a primary Heligmosomoides polygyrus infection in mice, and whether this could be related to impaired T cell function. Female BALB/c mice were fed a zinc-sufficient (Zn+; 60 mg/kg), a zinc-deficient (Zn-; 0.75 mg/kg) or an energy restricted (PF; 60 mg zinc/kg) diet. After four weeks, some mice in each dietary group were given a primary infection with 100 larvae; nutritional, parasitological and immunological parameters were assayed over the following five weeks. Liver zinc concentrations were significantly reduced in Zn- mice compared with Zn+ mice. In certain cases, PF mice also had reduced liver zinc concentrations, showing the negative effects of restricted food intake on zinc status. Zinc deficiency prolonged the course of a primary infection, with the effects being most evident five weeks post-infection when Zn+ mice had only 40% as many worms as Zn- mice. Parasite infection induced strong immunological responses in Zn+ mice in contrast to Zn- mice. The reduced production of IL-4 and IFN-γ, the reduced peripheral eosinophilia and reduced serum levels of IgE and IgG1 in Zn- mice were attributed to the zinc deficiency, whereas the reduced delayed type hypersensitivity response to parasite antigen and reduced production of IL-5 were in certain instances attributed to reduced energy intake rather than zinc deficiency. These results show that zinc deficiency significantly impairs functions normally attributed to both Th1 and Th2 cell populations, and that these alterations are associated with elevated worm numbers in zinc-deficient mice.     

The role of CD4+ and CD8+ T cells in protective immunity to the murine nematode parasite Trichuris muris

The role ofCD4⁺ and CD8⁺ T cells in protective immunity to Trichuris muris was studied in CD4⁺ or CD8⁺ or both CD4⁺ and CD8⁺ T cell-depleted BALB/c mice. To assess in vivo depletion of T-cell subsets, CD4⁺ and CD8⁺ T cells in the Peyer's patches, the mesenteric lymph nodes (MLN), and the spleens of mice treated with T cell-specific monoclonal antibodies (MoAbs) were analysed by FACS. CD4⁺ T cells were selectively depleted in mice injected with anti-CD4 MoAb i.p. and injection of anti-CD8 MoAb resulted in selective depletion ofCD8⁺ T cells. The expulsion ofl. muris was inhibited in CD4⁺ T cell-depleted mice and numerous worms were detected in the large intestine on days 14 and 21 after infection, although no suppression of protective immunity to T. muris was observed in CD8⁺ T cell-depleted mice. Moreover, there was no difference in suppression of protective immunity to T. muris between CD4⁺ T cell-depleted and both CD4⁺ and CD8⁺ T cell-depleted mice. These results indicate that CD4⁺ T cells play a central role in protective immunity to T. muris infection.     

Schistosoma mansoni: evidence that immunity in vaccinated and chronically infected CBA/Ca mice is sensitive to treatment with a monoclonal antibody that depletes cutaneous effector cells

Naive mice, mice vaccinated 4 weeks previously with radiation-attenuated cercariae of Schistosoma mansoni and mice infected 16 weeks previously with normal S. mansoni cercariae were treated with a rat monoclonal antibody (NIMP-R14), that has been reported elsewhere to recognize neutrophils selectively. The establishment of a primary schistosome population in naive mice was not affected by the administration of this reagent. In contrast, immune-dependent challenge elimination was reduced in both vaccinated and chronically infected mice following treatment with NIMP-R14. Maximal suppression of resistance in both vaccinated (67% mean reduction) and chronically infected (44% mean reduction) mice was achieved when NIMP-R14 was injected intraperitoneally on the day of challenge. The monoclonal was markedly less effective when administered on or after day 3. Analysis of the blood leucocyte profiles of vaccinated/NIMP-R14 treated mice showed that the monoclonal totally abrogated neutrophils from the peripheral circulation between days 1 and 6. Histological examination of the skin site of challenge revealed, however, that NIMP-R14 treatment had reduced the number of eosinophils and macrophages as well as neutrophils in the cutaneous tissues of vaccinated mice. The reaction site thus more closely resembled that of naive/challenged mice than that of untreated vaccinated/challenged mice. Although we have not been able to identify a specific effector cell from these studies, we have demonstrated clearly that a skin-located cellular effector mechanism contributes to immune resistance in both murine models.     

Protective immunity to malaria: studies with cloned lines of Plasmodium chabaudi and P. berghei in CBA/Ca mice. I. The effectiveness and inter-and intra-species specificity of immunity induced by infection

CBA/Ca mice were immunized by infection with cloned lines of Plasmodium berghei (isolates ANKA, KSP-11). Plasmodium chabaudi chabaudi (AS, CB) or Plasmodium chabaudi adami (DS) and then challenged with either homologous or heterologous parasites. Protective responses were assessed in immune mice relative to the controls by their ability to (i) extend the time taken for the mean parasitaemia to reach a predetermined level (1% or 0.1%) (ii) reduce peak parasitaemia (iii) resolve the parasitaemia sooner and/or (iv) control or eliminate recrudescences. At both the inter- and intra-species level, immunity appeared largely specific for the cloned line inducing it. At the interspecies level marginally effective cross-immunity was sometimes evident, thus P. berghei KSP-11 immune mice displayed some immunity against P.c. chabaudi AS, although immunity to this parasite was relatively ineffective against P. berghei ANKA or KSP-11. Cross-immunity was more apparent between the subspecies P.c. adami and P.c. chabaudi and between cloned lines of the latter parasite derived from the AS and CB isolates. These data reflect considerable inter- and intra-species structural and immunogenic differences in certain antigens of parasitized erythrocytes and merozoites, which have been identified in a number of murine malarias and associated with protective immunity. Similar differences recently identified in the equivalent antigens of the human parasite P. falciparum may therefore have important implications for protective immunity in man.     

The response of mice immune to Schistosoma mansoni to a challenge infection which bypasses the skin: evidence for two mechanisms of immunity

Mice which had developed immunity to reinfection with Schistosoma mansoni following exposure to 20 cercariae and mice which had been immunized against S. mansoni by exposure to 400 highly irradiated (20 krad) cercariae, were tested for their ability to resist a percutaneous cercarial challenge and an intravenous challenge with 5-day-old lung-stage schistosomula derived from the same cercariae. Although both types of immune mice showed a marked resistance to a cercarial challenge, only the infected mice showed a comparable immunity to an intravenous challenge with lung schistosomula. These results confirm earlier studies which suggest that the major attrition of a cercarial challenge in infected mice occurs at the post-lung stage, whilst the attrition of a challenge infection in mice immunized with highly irradiated cercariae takes place in the skin. They provide further evidence for two separate mechanisms of immunity against S. mansoni in mice.     

Protective immunity to malaria: studies with cloned lines of Plasmodium chabaudi chabaudi in CBA/Ca mice. III. Protective and suppressive responses induced by immunization with purified antigens

The protective effect of affinity purified antigen has been investigated in an experimental model for malaria which shows a well marked recrudescence of parasitaemia, a feature of the disease in man. A monoclonal antibody (MoAb) recognizing an epitope common to two genetically distinct cloned lines of Plasmodium chabaudi (AS and CB), was used to purify a Mr250,000 polymorphic schizont antigen (PSA) from these parasites. The purified preparations were then examined for the presence of specific and cross-reactive epitopes by immunoprecipitation with a panel of MoAb raised against P. chabaudi AS. When tested previously on smears of parasitized blood by immunofluorescence, or against lysates of parasitized erythrocytes by immunoprecipitation, most of these MoAb had been found to be AS specific. When either AS or CB affinity purified Mr250,000 PSA was used as the target, these same MoAb immunoprecipitated both antigens, and in some cases, a number of associated polypeptides (AP) which copurify with the Mr250,000 PSA. Subsequently, mice were immunized with either the purified AS or CB antigens in Freund's complete adjuvant (FCA). Prechallenge sera were compared by indirect immunofluorescence and immunoprecipitation. Sera from mice immunized with AS antigen reacted strongly with AS and cross-reacted with CB parasite preparations. Pre-challenge serum from CB antigen immunized mice reacted well with CB, but only faintly with AS preparations. In mice immunized with the AS antigen and then challenged with either AS or CB parasites, the initial parasitaemias were delayed in appearance and the height of the peak parasitaemia reduced, an effect which was most pronounced after challenge with homologous parasites. Only homologous challenge of the mice immunized with CB antigen produced statistically significant modification of the initial parasitaemia. In the immunized mice challenged with homologous parasites, the delayed appearance and slightly reduced peak of the primary parasitaemia was associated with delayed resolution of the patent parasitaemia and significant enhancement of the recrudescence.     

Protective immunity to malaria. Studies with cloned lines of Plasmodium chabaudi chabaudi and P. berghei in CBA/Ca mice. II. The effectiveness and inter- or intra-species specificity of the passive transfer of immunity with serum

Serum was obtained from CBA/Ca mice infected, reinfected or superinfected with parasites taken one or two syringe passages from cryopreserved reference stabilates derived from cloned lines of the AS or CB isolates of P.c. chabaudi. Serum was also collected from mice superinfected with parasites derived from a cloned line of P. berghei KSP-11. When injected into normal syngeneic recipients subsequently challenged with homologous or heterologous parasites, these sera mediated some or all of the following modifications to the breakthrough parasitaemias which invariably occurred (i) an extension of the pre-patent period (ii) an extension of the time taken for the parasitaemia to reach 2% (iii) a reduction of peak parasitaemia (iv) protraction of the initial peak of parasitaemia. These modifications were particularly evident with serum from superinfected mice and to a lesser extent with serum from animals reinfected once after recovery from a primary infection. Serum taken during the course of such a primary infection produced extended pre-2% periods, other effects being only marginal. Serum mediated modifications produced by reinfection and superinfection serum appeared largely species-specific with a limited degree of cross-reactivity. Intraspecific specificity was also apparent with serum from P.c. chabaudi AS or CB reinfected or superinfected mice, although marginal cross-immunity was again observed. When analysed by the fluorescent antibody technique on smears of methanol fixed parasitized erythrocytes, reinfection and superinfection sera were almost totally cross-reactive both within and across species. Preliminary evidence that parasites breaking through the effects of these sera may constitute a phenotypic antigenic variant is presented and possible mechanisms for the parasitaemia modifying effects of the various sera discussed.     

Protective immunity to malaria: studies with cloned lines of rodent malaria in CBA/Ca mice. IV. The specificity of mechanisms resulting in crisis and resolution of the primary acute phase parasitaemia of. Plasmodium chabaudi chabaudi and P. yoelii yoelii

Low numbers of parasites from cloned lines of the rodent malaria parasites, Plasmodium chabaudi chabaudi AS and P. yoelii yoelii A, injected into CBA/Ca mice produce acute but usually self-limiting infections. During crisis, i.e. 1-2 days after peak parasitaemia, 'pre-immune' mice experiencing such 'background' infections were reinfected intravenously with homologous parasites or parasites of heterologous strains or species. P. c. chabaudi AS pre-immune mice controlled an AS challenge with essentially the same kinetics as the background infection. Reinfection of AS pre-immune mice with the heterologous (CB and IP-PCI) P. c. chabaudi strains or P. chabaudi adami DS had little effect on the initial growth of these parasites, although eventually the parasitaemia was controlled. In contrast, a partial inhibitory effect on the growth of P. vinckei lentum DS was evident. Challenge with the non-lethal (A) or lethal (YM) variants of P. y. yoelii resulted in an increase in both the growth and virulence of these parasites. P. y. yoelii A pre-immune mice controlled a homologous challenge, but were less effective at controlling the YM variant. In addition, they were unable to clear rapidly a P. c. chabaudi AS or P. v. lentum DS challenge. Both the multiplication and virulence of P. berghei ANKA were enhanced. These findings demonstrate that resolution of the primary acute parasitaemia in P. c. chabaudi AS- and P. y. yoelii A-infected mice is predominantly mediated by species- and strain-specific mechanisms.     

Intranasal immunization with yeast-expressed 19 kD carboxyl-terminal fragment of Plasmodium yoelii merozoite surface protein-1 (yMSP119) induces protective immunity to blood stage malaria infection in mice

Variable protection against malaria blood-stage infection has been demonstrated in mice following parenteral immunization with the highly conserved 19 kD carboxylterminal fragment of the merozoite surface protein-1 (MSP1₁₉) using CFA/IFA and other adjuvants. Here we show that intranasal immunization of BALB/C mice with yeast expressed Plasmodium yoelii MSP1₁₉ plus a mixture of native and recombinant cholera toxin B subunit, could induce serum MSP1₁₉-specific antibodies at titres ranging from 20 000 to 2 560 000. The Ig subclass responses were predominantly G1 and G2b. Intranasal immunization led to protection following challenge (peak parasitaemia < 1%) in mice with the highest MSP1₁₉-specific titre (≥ 640 000). In two of the three protected mice, a peak parasitaemia of 0.1%–1% was followed by a boost of the antibody response whereas one of the three protected mice did not boost its antibody response after a peak parasitaemia of 0.02%. In unprotected mice, antibody levels rose, then fell, following the detection of parasites in the peripheral blood. CD4⁺ T cell-depletion abrogated the ability of the mice to boost their antibody response following challenge. These data demonstrate the potential for intranasal immunization with MSP1₁₉ to protect against malaria .     

Seroprevalence of antibody to influenza A(H1N1)pdm09 attributed to vaccination or infection,before and after the second (2010) pandemic wave in Australia

Objectives

Historical records of influenza pandemics demonstrate variability in incidence and severity between waves. The influenza A(H1N1)pdm09 pandemic was the first in which many countries implemented strain-specific vaccination to mitigate subsequent seasons. Serosurveys provide opportunity to examine the constraining influence of antibody on population disease experience.

Design

Changes in the proportion of adults seropositive to influenza A(H1N1)pdm09over the 2009/10 (summer) interepidemic period and 2010 (winter) influenza season were measured to determine whether there was a temporal relationship with vaccine distribution and influenza activity, respectively.

Setting

Australia.

Sample

Plasma samples were collected from healthy blood donors from seven cities at the end of the first wave (November 2009), and before (March/April 2010) and after (November 2010) the subsequent influenza season.

Main outcome measures

Haemagglutination inhibition (HI) assays were performed to assess reactivity of plasma against A(H1N1)pdm09, and the proportion seropositive (HI titre ≥ 40) compared over time, by age group and location.

Results

Between the 2009 and 2010 influenza seasons, the seropositive proportion rose from 22% to 43%, an increase observed across all ages and sites. Brisbane alone recorded a significant rise in seropositivity over the 2010 influenza season – from a baseline of 35% to 53%. The seropositive proportion elsewhere was ≥40% pre-season, and did not rise over winter.

Conclusions

A vaccine-associated increase in seropositive proportion preceding the influenza season correlated with low levels of disease activity in winter 2010. These observations support the role of immunisation in mitigating the ‘second wave’ of A(H1N1)pdm09, with timing critical to ensure sustained herd protection.     

Adjuvant guided polarization of the immune humoral response against a protective multicomponent antigenic protein (Q) from Leishmania infantum. A CpG + Q mix protects Balb/c mice from infection

It has been shown that vaccination with three doses of the Leishmania infantum poly-protein Q containing five genetically fused antigenic determinants from the Lip2a, Lip2b, H2A and P0 proteins, mixed with BCG induces clearance of parasites in 9 out of 10 Leishmania infantum-infected Beagle dogs, in addition to clinical protection. In the present paper we analysed the immunogenic potential of the poly-protein Q and the specificity and polarization of the response against the antigenic determinants of Q when mixed with various adjuvants. The data showed that the Q protein had high intrinsic immunogenic potential and that it was able to induce a long-lasting IgG response. The IgM immunogenic potential of the poly-protein was mainly due to the LiP2a and LiP2b determinants, whereas the IgG immunogenic potential was mainly due to the LiP2a component. It was observed that the protein itself elicited a mixed IgG2a/IgG1 response and that the determinants of Q were endowed with different IgG2a/IgG1 potential. It was also observed that the adjuvants did not influence the intensity or specificity of the IgM response but that they modulated the intensity, the specificity and the polarization of the IgG response against the determinants of Q. CpG-ODN motifs or double-stranded DNA plasmids containing CpG motifs when mixed with Q induced a predominant IgG2a response mainly observed at early stages post-immunization. The data showed that a CpG + Q mix induced significant protection against L. infantum infection in Balb/c mice.     

The SNPs (-1654C/T, -1641A/G and -1476A/T) of protein C promoter are associated with susceptibility to pulmonary thromboembolism in a Chinese population

Background

Pulmonary thromboembolism (PTE) is a common and potentially lethal disease. It is significant to investigate the gene mutations of protein C for clarifying the etiology of PTE. In this present study, we investigated the promoter region polymorphism sites including -1654C/T, -1641A/G and -1476A/T of the protein C gene in a Chinese population.

Methods

A total of 110 cases of PTE and one hundred and ninety healthy controls in a Chinese population were genotyped for three polymorphisms (-1654C/T, -1641A/G and -1476A/T) of the protein C promoter. The statistical analysis was performed by Stata 11.0.

Results

The single nucleotide polymorphisms (SNPs) (-1654C/T, -1641A/G and -1476A/T) in protein C gene were associated with the susceptibility to PTE in Chinese population. According to the binary logistic regression analysis, the independently significant risk factors for PTE were the complications of deep vein thrombosis (DVT) or cancer, history of operation or injury, and the homozygous carriers of the TT genotype (protein C -1654C/T).

Conclusions

The SNPs (-1654C/T, -1641A/G and -1476A/T) of protein C promoter gene are associated with the susceptibility to PTE in a Chinese population. Especially, the homozygous carriers of genotype TT (-1654C/T) increase the risk of PTE in a Chinese population. Confirmation of our preliminary observations in a larger scale study is needed.     

Th1 immune response to Plasmodium falciparum recombinant thrombospondin‐related adhesive protein (TRAP) antigen is enhanced by TLR3‐specific adjuvant,poly(I:C) in BALB/c mice

Sporozoite‐based malaria vaccines have provided a gold standard for malaria vaccine development, and thrombospondin‐related adhesive protein (TRAP) serves as the main vaccine candidate antigen on sporozoites. As recombinant malaria vaccine candidate antigens are poorly immunogenic, additional appropriate immunostimulants, such as an efficient adjuvant, are highly essential to modulate Th1‐cell predominance and also to induce a protective and long‐lived immune response. In this study, polyinosinic:polycytidylic acid [poly(I:C)], the ligand of TLR3, was considered as the potential adjuvant for vaccines targeting stronger Th1‐based immune responses. For this purpose, BALB/c mice were immunized with rPfTRAP delivered in putative poly(I:C) adjuvant, and humoural and cellular immune responses were determined in different immunized mouse groups. Delivery of rPfTRAP with poly(I:C) induced high levels and titres of persisted and also high‐avidity anti‐rPfTRAP IgG antibodies comparable to complete Freund's adjuvant (CFA)/incomplete Freund’s adjuvant (IFA) adjuvant after the second boost. In addition, rPfTRAP formulated with poly(I:C) elicited a higher ratio of IFN‐γ/IL‐5, IgG2a/IgG1, and IgG2b/IgG1 than with CFA/IFA, indicating that poly(I:C) supports the induction of a stronger Th1‐based immune response. This is a first time study which reveals the potential of rPfTRAP delivery in poly(I:C) to increase the level, avidity and durability of both anti‐PfTRAP cytophilic antibodies and Th1 cytokines.     

Effect of dietary approaches to stop hypertension (DASH) diet,high in animal or plant protein on cardiometabolic risk factors in obese metabolic syndrome patients: A randomized clinical trial

AimsThis study aimed to investigate the effect of replacing plant proteins with animal proteins in the dietary approaches to stop hypertension (DASH) diet on cardiometabolic risk factors in obese metabolic syndrome participants.MethodsIn this double-blind randomized controlled clinical trial, 90 obese patients with metabolic syndrome, aged 30–70 years were randomly allocated into the DASH diet based on plant or animal proteins for 8 weeks. Fasting blood samples were collected to assess the biochemical markers. Also, blood pressure, weight, and waist circumference (WC) were measured at the beginning and end of the trial.ResultsThe participants in both groups experienced significant reductions in the fasting plasma glucose (FPG), systolic blood pressure (SBP) and diastolic blood pressure (DBP), triglyceride (TG) concentrations, weight and WC. However the reduction in FPG and SBP was higher in the plant-based DASH group, compared to the animal-based DASH group, after adjustment for weight change. No significant changes were found within or between groups with regard to total cholesterol, LDL-C, HDL-C.ConclusionsSubstituting plant proteins with animal proteins in the DASH diet improves FPG and SBP in obese individuals with metabolic syndrome, independent of weight change. IRCT registration number: IRCT20090203001640N16.     

Lack of sequence variations in the C4b-BP β-chain in patients with type III protein S deficiency bearing the Ser 460 to Pro mutation: description of two new intragenic isomorphisms in the C4b-BP β-chain gene (C4BPB)

Type III protein S (PS) deficiency, characterized by low levels of free PS and normal total PS levels, is often associated with the Ser 460 to Pro substitution. However, some patients bearing this mutation have normal PS levels, suggesting that another gene defect may account for this phenotype. We postulated that this defect was located in the C4b-BP β-chain gene (C4BPB) and searched for a mutation in the coding regions of this gene in 35 propositi with type III PS deficiency and bearing the Ser 460 to Pro mutation. No mutations explaining the phenotype of type III PS deficiency were identified. We did, however, find two frequent nucleotide changes, one being located in the donor splice site of intron d and the second in the codon corresponding to Asn 137. We used these two polymorphisms to establish C4BPB gene haplotype in five informative type III PS-deficient families and exclude a role of the C4BPB gene in this phenotype of three of them. Finally, increased C4b-BP β-chain levels were not responsible for the phenotype of type III PS deficiency as the C4BPB haplotype did not correlate with C4b-BP β-chain levels.