A novel hepatitis B virus mutant with A-to-G at nt551 in the surface antigen gene

AIM: Hepatitis B surface antigen (HBsAg) mutant of hepatitis B virus (HBV) is one of the important factors that result in immune escape and cause failure of immunization. In this study we reported and characterized a novel HBV mutant with A-to-G at nt551 and intended to provide theoretical data for prevention of HBV infection in China.METHODS: A methodology comprising polymerase chain reaction (PCR) amplifying, M13 bacteriophage cloning and nucleotide sequencing was used to analyze the sera of the pediatric patient who was hepatitis B (HB) immune failure.Expression plasmids containing the mutant S gene and a wild-type (adr) S gene were constructed respectively and the recombinant HBsAg were expressed in COS-7 cells under the regulation of SV40 early promoter. The recombinant proteins were investigated for their immunological reactivity with different monoclonal antibodies (mAb) against ‘a’determinant and vaccine-raised human neutralizing antibodies.RESULTS: It was found that there was a new point mutation at nt551 of the HBV (adr) genome from A to G, leading to a substitution of methionine (Met) to valine (Val) at position 133 in the ‘a’ determinant of HBsAg. Compared to the wildtype HBsAg, the binding activity of the muant HBsAg to mAbs (A6, All and S17) and to vaccine-raised human antihepatitis B surface antibody (anti-HBs) decreased significantly.CONCLUSION: According to the facts that the patient has been immunized with HB vaccine and that the serum is antiHBs positive and HBsAg negative, and based on the nucleotide sequence analysis of the mutant HBV S gene and its alteration of antigenicity, the HBV is considered to be a new vaccine-induced immune escape mutant different from the known ones.     

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

Objective:To 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 domainⅡ(PvAMA1-DⅡ)and regionⅡof the Duffy binding protein(PvDBPⅡ).and to analyze the immunogenie properties of these predicted epitopes.Methods:3-D structures of amino acid haplotypes from Sri Lanka(available in GeneBank)of PvMSP-1_(19)(n=27),PvAMA1-DⅡ(n=21)and PvDBPⅡ(n=33)were modeled.SEPPA,selected as the best online server was used for conformational epitope predictions,while prediction and moodeling of protein structuve and properties related to immunogenicity was carried out with Geno3D server.SCRATCH Protein Server,NetSurfP Server and standaloneroftware,Genious 5.4.4.Results:SEPPA revealed that regions of predicted conformational epitopes formed 4 clusters in PvMSP-I_(19),and 3 clusters each in PvAMA1-DⅡand PvDBPⅡ,all of which displayed a high degree of hydrophilicity,contained solveut exposed residues,displayed high probability of antigenicity and showed positive antigenic propensity values,that indicated high degree of immunogenicity.Conclusions:Findings 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 invertigations in in vivo animal models.     

西藏林芝地区间日疟原虫PvMSP-3α多态性研究

【摘要】 目的 分析西藏林芝地区间日疟原虫遗传多态性。 方法 以间日疟原虫裂殖子表面蛋白3α（Plasmodium vivax merozoite surface protion genes 3α,PvMSP-3α）为分子标志,利用PCR-RFLP技术对西藏林芝间日疟原虫多态性进行分析。 结果 共发现2种类型的MSP-3α基因,多数为A型（90.3%）,B型较少（9.7%）,无混合感染。PCR-RFLP分析MSP-3α基因存在较低多态性。 结论 西藏林芝地区间日疟原虫的遗传多态性较低。     

Biological role of surface Toxoplasma gondii antigen in development of vaccine

AIM: To analyze the biological role of the surface antigen of Toxoplasma gondii (T gondii) in development of vaccine. METHODS: The surface antigen of T gondii (SAG1) was expressed in vitro. The immune response of the host to the antigen was investigated by detection of specific antibody reaction to SAG1 and production of cytokines. Mice were immunized with recombinant SAG1 and challenged with lethal strain of T gondii RH. The monoclonal antibody to r-SAG1 was prepared and used to study the effects of SAG1 on T gondii tachyzoites under electromicroscope. RESULTS: The mice immunized with recombinant SAG1 delayed death for 60 h compared to the control group. The recombinant SAG1 induced specific high titer of IgG and IgM antibodies as well as IFN-γ, IL-2 and IL-4 cytokines in mice. In contrast, IL-12, IL-6 and TNF-αwere undetectable. When T gondii tachyzoites were treated with the monoclonal antibody to r-SAG1, the parasites were gathered together, destroyed, deformed, swollen, and holes and gaps formed on the surface. CONCLUSION: SAG1 may be an excellent vaccine candidate against T gondii. The immune protection induced by SAG1 against T gondii may be regulated by both hormone- and cell-mediated immune response.     

Immunogenicity and immunizing protection effect of GAMA gene DNA vaccine on Plasmodium berghei

Objective: To explore the effect of immunogenicity and immunizing protection of GAMA gene DNA vaccine, which was related with merozoite, ookinete and sporozoite invasion. Methods:Gene fragments were obtained using PCR technique and eukaryotic expression vector(containing immunostimulatory sequence) was built. BALB/c mice were divided into PBS control group, empty vector control group and study group and were immunized at week 0, 3 and 6 respectively. Blood was collected 2 weeks after each immunization and serum was separated to detect the Ig G, Ig G1 and Ig G2 a levels. Spleen of mice was obtained for preparation of splenic mononuclear cell and the cytokine IL-4 and IFN-αlevels were detected. Indirect immunofluorescence and western blot were employed to verify the specificity of antiserum. Sporozoite and merozoite invasion were used respectively to detect the immune protective effect 2 weeks after the third immunization. Ookinete conversion rate in vitro and oocyst numbers of mosquito stomach were observed to evaluate the transmission-blocking levels. Results: In GAMA DNA vaccine group: antiserum could be combined with recombinant protein specifically and green fluorescence signals of merozoite, ookinete and sporozoite were observable, while specific fragments and fluorescence signals were not observable in empty vector group. Compared with control group, specific Ig G in DNA vaccine immunity group significantly increased(P0.01), and Ig G1 and Ig G2 a all increased(P0.01). IL-4, IFN-αcontent in study group significantly increased, compared with control group(P0.01). GAMA DNA vaccine immunity could not obviously block the erythrocyte-stage infection(caused by sporozoite invasion); compared with control group, liver worm load was slightly reduced(P0.05), and antiserum ookinete numbers(cultured in vitro) had no significant difference with oocyst numbers of mosquito stomach in DNA vaccine group. Conclusions:GAMA has good antigenicity, which could stimulate the body to produce specific immune responses; while DNA vaccine immunity could not play a good protective effect, the effect of which is only limited to the slight reduction of liver worm load, and has no obvious erythrocytestage protective effect and transmission-blocking effect. Therefore, trying other immunization strategies for further research on the value of GAMA(as multi-stage antigen vaccine and multistage combined vaccine components of the life-cycle of plasmodium) is necessary.     

High expression level of soluble SARS spike protein mediated by adenovirus in HEK293 cells

AIM: To develop a highly efficacious method for preparation of soluble SARS S-protein using adenovirus vector to meet the requirement for S-protein investigation. METHODS: The human adenovirus vector was used to express the soluble S-protein (corresponding to 1-1190 amino acids) fused with Myc/His tag using codon-optimized gene construct in HEK239 cells. The recombinant adenovirus bearing S-protein gene was generated by ligation method. The expressed S-protein with Myc/His tag was purified from culture medium with Ni-NTA agarose beads followed by dialysis. The S-protein was detected by Western blot and its biologic activity was analyzed by binding to Vero cells. RESULTS: Under the conditions of infection dose (MOI of 50) and expression time (48 h), the high-level expression of S-protein was obtained. The expression level was determined to be approximately 75μg/106 cells after purification. Purified soluble S-protein was readily detected by Western blot with anti-Myc antibody and showed the ability to bind to surface of Vero cells, demonstrating that the soluble S-protein could remain the biologic activity in the native molecule. CONCLUSION: The high-level expression of S-protein in HEK293 cells mediated by adenovirus can be achieved under the optimized expression conditions. The proteins possess the biologic activity, which lays a foundation for further investigation of S-protein biological function.     

Expression and immunoreactivity of an epitope of HCV in a foreign epitope presenting system

AIM: To construct and highly express an epitope of hepatitis C virus (HCV) in a foreign epitope presenting vector based on an insect virus, and to study the antigenicity of the epitope. METHODS: The HCV epitope sequence (amino acid residues 315 to 328: EGHRMAWDMMMNWS) of the El region was constructed at different positions of a foreign epitope presenting vector based on an insect virus, flock house virus (FHV) capsid protein encoding gene as a vector, and expressed in E. coli cells. Western blotting and ELISA were used to detect the immunoreactivity of these recombinant proteins. RESULTS: The gene encoding of the concerned B-cell epitope of HCV El envelope protein was expressed on FHV capsid carrier protein at positions I1 (aa 106), 12 (aa 153) and 13 (aa 305), respectively, on the surface of FHV capsid protein. The recombinant proteins in this system could be highly expressed in more than 40% of total cell protein of E. coli BL21. All the expressed recombinant proteins were in inclusion body form, and showed obvious immunoreactivity by Western blotting. Further purified recombinant proteins were detected by indirect ELISA as coating antigen respectively. All recombinant proteins could still show immunoreactivity. CONCLUSION: The epitope of HCV El envelope protein can be highly expressed in FHV carrier system as a chimeric protein with high immunoreactivity. This system has multiple entry sites conferring many possible conformations closer to the native one for a given sequence.     

Immunological response in alcoholic liver disease

The development of alcoholic liver disease (ALD) can be attributed to many factors that cause damage to the liver and alter its functions. Data collected over the last 30 years strongly suggests that an immune component may be involved in the onset of this disease. This is best evidenced by the detection of circulating autoantibodies, infiltration of immune cells in the liver, and the detection of hepatic aldehyde modified proteins in patients with ALD. Experimentally, there are numerous immune responses that occur when proteins are modified with the metabolites of ethanol. These products are formed in response to the high oxidative state of the liver during ethanol metabolism, causing the release of many inflammatory processes and potential of necrosis or apoptosis of liver cells. Should cellular proteins become modified with these reactive alcohol metabolites and be recognized by the immune system, then immune responses may be initiated. Therefore, it was the purpose of this article to shed some insight into how the immune system is involved in the development and/or progression of ALD.     

No requirement of HCV 5‘NCR for HCV-like particles assembly in insect cells

AIM: To express all three HCV structural proteins in the presence or absence of HCV 5‘‘NCR to investigate the requirement of 5‘NCR for the assembly of HCV-like particles in insect cells. METHODS: HCV structural protein encoding sequences CEIE2 and 5‘‘NCR-CEIE2 were amplified with PCR. Recombinant baculovirus were constructed with recombinant DNA techniques. HCV structural proteins expressed in insect cells were analyzed by immunofluorescence and SDS-PAGE. Immunoprecipitation experiment of insect cell lysates with anti-E2 monoclonal antibody (Mab) was carried out and the immunoprecipitated proteins were subjected to SDS-PAGE and immunoblotting with anti-C, anti-E2 Mabs and HCV positive serum. The virus-like particles in insect cells were visualized by electron microscopy (EM). The HCV-like particles were purified by sucrose gradient centrifugation and identified by EM and immune aggregation EM. RESULTS: The recombinant baculovirus reBV/CEIE2 containing HCV C, E1, E2 genes and reBV/CS containing the same structural protein genes plus 5‘‘NCR were constructed. The insect cells infected with either reBV/CE1E2 or reBV/CS expressed HCV C, E1 and E2 proteins with amolecular weight of 20 kD, 35 kD and 66 kD respectively. The results of immunoprecipitation and the immunoblotting revealed the coimmunoprecipitation of C, E1, and E2 proteins, indicating the interaction of HCV structural proteins expressed in insect cells. Electron microscopy of insect cells infected with reBV/CE1E2 or reBV/CS demonstrated spherical particles (40 to 60 nm in diameter) similar to the HCV virions from sera or hepatic tissues of HCV infected humans. The HCV-like particles were partially purified by sucrose gradient centrifugation, and the purified VLPs showed immuno-reactivity with anti-HCV antibodies.CONCLUSION: HCV 5‘‘NCR is not required for the assemblyof HCV-like particles in insect cells, HCV core and envelope proteins are sufficient for viral particle formation.     

Prokaryotical expression of structural and non-structural proteins of hepatitis G virus

AIM To study the epitope distribution of hepatitis G virus(HGV) and to seek for the potential recombinant antigensfor the development of HGV diagnositic reagents.METHODS Fourteen clones encompassing HGV genefragments from core to NS3 and NS5 were constructedusing prokaryotic expression vector pRSET and (or)pGEX,and expressed in E.coli.Western blotting andELISA were used to detect the immunoreactivity of theserecombinant proteins.RESULTS One clone with HGV fragment from core to E1(G1),one from E2 (G31),three from NS3 (G6,G61,G7),one from NS5B (G821) and one chimeric fragment fromNS3and NS5B (G61-821) could be expressed well andshowed obvious immunoreactivity by Western blotting.One clone with HGV framment from NSSB (G82) was alsowell expressed,but could not show immunoreactivity byWestern blotting.No obvious expression was found in theother six clones.All the expressed recombinant proteinswere in inclusion body form,except the protein G61 whichcould be expressed in soluble form.Further purifiedrecombinant proteins G1,G31,G61,G821 and G61-821were detected in indirected ELISA as coating antigenrespectively.Only recombinant G1 could still showimmunoreactivity,and the other four recombinantproteins failed to react to the HGV antibody positive sera.Western blotting results indicated that the immunoactivityof these four recombinant proteins were lost duringpurification.CONCLUSION Core to E1,E2,NS3 and NS5 fragment ofHGV contain antigenic epitopes,which could be producedin prokaryotically expressed recombinant proteins.Ahigh-yield recombinant protein (G1) located in HGV coreto E1 could remain its epitope after purification,whichshowed the potential that G1 could be used as a coatingantigen to develop an ELISA kit for HGV specific antibodydiagnosis.     

Reactivity of sera from cases of Plasmodium vivax malaria towards three recombinant antigens based on the surface proteins of the parasite

Sera collected in South Korea, from 61 cases of Plasmodium vivax malaria and, as controls, 40 healthy volunteers, were tested in ELISA for IgG or IgM reacting with any of three recombinant P. vivax proteins. The antigens used, representing the parasite's major merozoite surface protein (MSP), circumsporozoite surface protein (CSP) and Duffy-binding protein (DBP), had all been expressed in an Escherichia coli system and purified. The ELISA results were recorded as optical densities (OD). The highest ratio observed between the mean OD for a malaria serum and that for a control serum was that for IgG against MSP, although CSP gave a higher ratio than MSP or DBP in the IgM ELISA. In the ELISA for IgG, the OD for MSP were found to be correlated with those for DBP (r = 0.53; P < 0.5) but the OD for CSP were not correlated with those for MSP or DBP. As the most intense reactions observed were those between the IgG from the malaria sera and the recombinant MSP, the latter antigen may be useful in diagnostic tests and as a component of any vaccine used to protect against P. vivax malaria.     

Naturally acquired antibody responses to the components of the Plasmodium falciparum merozoite surface protein 1 complex

Merozoite surface protein 6 (MSP6) and 7 (MSP7) of Plasmodium falciparum are peripheral membrane proteins whose cleaved products, MSP636, MSP722 and MSP719, are found on the merozoite surface as components of a non-covalently bound complex which also contains four polypeptides derived from merozoite surface protein 1 (MSP1). We have expressed both the precursor regions and the processed mature products of MSP6 and MSP7 in Escherichia coli and showed that these recombinant proteins react with human immune sera. In a set of sera collected from individuals living in malaria-endemic areas of Southern-central Vietnam, antibodies to the mature polypeptides of MSP636 and MSP722 were detected in 50.6 and 85.6% of the serum samples, whereas antibodies to the precursor regions of MSP6 and MSP7 were detected in only 12.1 and 42.5% of the serum samples, respectively. The predominant subclass of anti-MSP6 antibodies was IgG1, whereas the predominant subclass of anti-MSP7 antibodies was IgG3. In the same set of serum samples, the antibody responses to MSP119 are predominantly IgGI, whereas antibodies to merozoite surface protein 4 (MSP4) are mainly IgG3. This data is consistent with the proposition that, during malaria infection, variable proteins induce responses that are predominantly of the IgG3 isotype, and conserved proteins induce responses that are predominantly IgG1. The antibodies to MSP6, MSP7 and MSP119 all decreased at the time of infection, but increased during the convalescent period. No correlation was observed between the antibodies at the commencement of the study and absence of parasitaemia during surveillance in this population.     

Antibodies to Plasmodium falciparum and Plasmodium vivax merozoite surface protein 5 in Indonesia: species-specific and cross-reactive responses

BACKGROUND: Merozoite surface protein (MSP) 5 is a candidate antigen for a malaria vaccine. In cross-sectional and longitudinal studies, we measured MSP5 antibody responses in Papuans with acute Plasmodium falciparum malaria, Plasmodium vivax malaria, and mixed P. falciparum and P. vivax malaria and in those with past exposure. METHODS: Enzyme-linked immunosorbant assay (ELISA) was used to quantitate antibody responses to P. falciparum MSP5 (PfMSP5) and P. vivax MSP5 (PvMSP5) in 82 subjects with P. falciparum infection, 86 subjects with P. vivax infection, 85 subjects with mixed infection, and 87 asymptomatic individuals. Longitudinal responses through day 28 were tested in 20 persons. Cross-reactivity was tested by competition ELISA. RESULTS: PfMSP5 or PvMSP5 immunoglobulin (Ig)Gwas detected in 39%-52% of subjects, and IgM was detected in 44%-72%. IgG responses were distributed equally between IgG3 and IgG1 for PfMSP5 but were predominantly IgG3 for PvMSP5. Although IgG responses were generally specific for PfMSP5 or PvMSP5, cross-species reactivity was found in 7 of 107 dual-positive responders. No significant difference was seen in the magnitude, frequency, or subclass of PfMSP5 or PvMSP5 IgG antibodies between groups. There was no significant association between antibody responses and therapeutic response. CONCLUSION: PfMSP5 and PvMSP5 were frequently recognized by short-lived, species-specific antibodies. Although infrequent, the cross-reactive MSP5 antibodies indicate that an appropriately formulated vaccine may elicit and/or enhance cross-species recognition, which may be very useful in areas where both parasites are endemic.     

Anti-Plasmodium vivax duffy binding protein antibodies measure exposure to malaria in the Brazilian Amazon

Plasmodium vivax Duffy binding protein (DBP) is functionally important in the erythrocyte invasion process and provides a logical target for vaccine-mediated immunity. In the current study, we demonstrated that DBP is naturally immunogenic in different populations of the Brazilian Amazon, and the proportions of DBP IgG positive subjects increased with exposure to malaria, reaching a peak in those subjects with long-term exposure (> 15 years) in the Amazon area. This profile of antibody response was significantly different from the one observed for the P. vivax merozoite surface protein 1 (MSP1(19)), which was relatively uniform in areas with markedly different levels of malaria transmission. In a small sample of adults with symptomless P. vivax infection, we could not detect any significant correlation between antibodies against these P. vivax proteins and asymptomatic infection. Our study provided an additional insight by demonstrating cumulative exposure as a determinant that acts independently of host age in generation of anti-DBP IgG response.     

Naturally acquired antibodies to polymorphic and conserved epitopes of Plasmodium falciparum merozoite surface protein 3

Many studies on the role of merozoite surface protein 3 (MSP3) in immunity against malaria have focused on a conserved section of MSP3. New evidence suggests that polymorphic sequences within MSP3 are under immune selection. We report a detailed analysis of naturally-acquired antibodies to allele-specific and conserved parts of MSP3 in a Kenyan cohort. Indirect and competition ELISA to heterologous recombinant MSP3 proteins were used for antibody assays, and parasites were genotyped for msp3 alleles. Antibody reactivity to allele-specific and conserved epitopes of MSP3 was heterogeneous between individuals. Overall, the prevalence of allele-specific antibody reactivity was significantly higher (3D7-specific 54%, K1-specific 41%) than that to a recombinant protein representing a conserved portion of C-terminal MSP3 (24%, P < 0.01). The most abundant IgG subclass was IgG3, followed by IgG1. Allele-specific reactivity to the K1-type of MSP3 was associated with a lower risk of clinical malaria episodes during a 6-month follow-up in individuals who were parasitized at the start of the malaria transmission season (Relative risk 0.41 with 95% confidence interval 0.20-0.81, P = 0.011). The potential importance of allele-specific immunity to MSP3 should be considered in addition to immunity to conserved epitopes, in the development of an MSP3 malaria vaccine.     

Plasmodium falciparum genotyping by microsatellites as a method to distinguish between recrudescent and new infections

In vivo tests for susceptibility to antimalarial drugs require molecular methods to distinguish recrudescence from new infection. The most commonly used DNA markers (merozoite surface proteins [MSPs]) are under immune selective pressure, which might lead to misclassification. We evaluated immunologically neutral microsatellite markers in blood samples collected during a drug efficacy trial in Rwanda. Fifty percent of the infections classified as recrudescent by MSP were classified as new by microsatellite markers. Reciprocally, 23.3% of infections classified as recrudescent by microsatellite markers were identified as new by MSP. In drug efficacy studies, microsatellite markers should complement MSP genotyping to distinguish a recrudescence from a new infection.     

大肠埃希菌表达的恶性疟原虫裂殖子表面蛋白MSP1-42的免疫原性

目的纯化大肠埃希菌Rosettagami（DE3）表达的可溶性裂殖子表面蛋白1C末端蛋白（MSP1-42,3D7株）,检测其体外抑制恶性疟原虫生长的效果。方法利用大肠埃希菌Rosettagami（DE3）为宿主菌诱导表达MSP1-42,用带组氨酸标签的镍柱纯化可溶性的MSP1-42。6只新西兰白兔随机分为免疫组和对照组,每组3只。用MSP142与弗氏佐剂乳化后,皮下注射,抗原免疫剂量每次为200“g／只,共免疫4次,每次间隔2周。佐剂对照组以PBS代替抗原同法免疫。免疫前及末次免疫2周后取血,用酶联免疫吸附试验和间接荧光抗体试验检测血清中特异性抗体及其与天然抗原的反应,用含10％和20％免疫血清的培养基体外培养恶性疟原虫（海南分离株,Fcc1／HN）,检测免疫血清体外抑制恶性疟原虫生长的效果。结果经镍柱纯化后获得纯度为95％以上的MSP1-42蛋白;免疫组个体在第4次免疫后血清特异性抗体的滴度依次为1：640000、1：640000、1：160000,间接荧光抗体试验检测表明MSP1-42免疫兔血清与恶性疟原虫表面蛋白有阳性反应;免疫血清能抑制恶性疟原虫在体外生长,在10％浓度时,3只免疫兔血清的抑制率依次为（51．94-24．2）％、（29．4±8．6）％和（86．7±7．4）％,在20％浓度时,抑制率分别为（93．3±7．5）％、（65．3±10．6）％和（96．4±1．0）％。结论大肠埃希菌Rosettagami（DE3）表达的MSP142蛋白免疫血清能识别恶性疟原虫天然抗原,体外培养能抑制恶性疟原虫的生长。     

Analysis of naturally acquired antibody responses to the 19-kd C-terminal region of merozoite surface protein-1 of Plasmodium vivax from individuals in Sanliurfa, Turkey

Plasmodium vivax is the second most prevalent global Plasmodium species causing malaria after P. falciparum. These two Plasmodium spp. co-exist in most endemic areas, apart from west and central Africa, which has only P. falciparum. However, southeastern Turkey is one of the exceptional regions with the sole presence of P. vivax infection, where a thorough epidemiologic survey has not been performed. Here, we report for the first time the identification of naturally acquired antibodies against the 19-kd C-terminal region of the merozoite surface protein-1 of P. vivax (PvMSP1(19)), using ELISA, from residents in the Sanliurfa region of southeastern Turkey. Among the 82 samples from patients with patent P. vivax malaria, 85% of the individuals were sero-reactive to PvMSP1(19). Particularly, 69.5% of the subjects were positive for IgM, 53.6% were positive for IgG (predominantly IgG1 and IgG3), and 7.3% were positive for IgA.     

Humoral immune responses against Plasmodium vivax MSP1 in humans living in a malaria endemic area in Flores, Indonesia

The aim of this study was to evaluate the relationship among age, parasitemia status, spleen size, hematocrit, and antibody levels to Plasmodium vivax merozoite surface protein 1 (MSP1) in individuals chronically exposed to P. vivax. Subjects were recruited from the population of three adjacent villages on the Island of Flores in Indonesia where malaria transmission is hyperendemic and tropical splenomegaly syndrome is highly prevalent. Subjects were evaluated for spleen size, hematocrit, presence of parasitemia, and presence of antibodies to a recombinant peptide consisting of 90 amino acids from the carboxy terminus of MSP1. Fifty-seven percent of 2-4 year olds, 45% of 5-9 years old, and 7% of > or = 15 years old were parasitemic; 99% of the > or = 15 years old had splenomegaly, and 31% of them had Hackett 4 or 5 spleens. The frequency of antibody positivity to MSP1 antigen in ELISA increased with age reaching a maximum of 89% in > or = 20 years old. The frequency of antibody positivity to MSPI also increased with spleen size, and with a decline in the prevalence of parasitemia.     

Schistosoma haematobium infection affects Plasmodium falciparum-specific IgG responses associated with protection against malaria

We have previously shown that antibody responses directed to Plasmodium falciparum merozoite surface protein (MSP)‐1, MSP‐2 and glutamate‐rich protein (GLURP) are associated with anti‐malarial protection in residents of the Niakhar area of Senegal. In the same area, urinary schistosomiasis is frequent and we therefore assessed the possible influence of Schistosoma haematobium infection on these protective anti‐malarial IgG responses. After adjustment for confounders, we found that the levels of IgG1 directed to MSP1 and GLURP were significantly lower in helminth carriers. The higher circulating levels of interleukin (IL)‐10 present in the plasma of co‐infected individuals were associated with decreased anti‐plasmodial IgG responses, particularly of those directed to MSP‐2. Our data thus reveal a modulation of P. falciparum‐specific immune responses in the presence of a trematode helminth infection, potentially increasing infected individuals’ risk of plasmodial infection or disease.