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1.
P Millet C Chizzolini R A Wirtz I Bathurst J R Broderson G H Campbell W E Collins 《European journal of immunology》1992,22(2):519-524
In previous studies, Saimiri sciureus boliviensis monkeys have been immunized with four recombinant proteins reproducing part of the circumsporozoite (CS) protein of Plasmodium vivax sporozoites (NS1(81) V20, rPvCS-1, rPvCS-2, rPv-CS-3), or with irradiated sporozoites of P. vivax Salvador I strain. To analyze the antibody response elicited against epitopes located outside the immunodominant repeat region of the CS protein, serum samples from these animals were tested for their ability to inhibit the in vitro development of liver stages of P. vivax VK247 strain, characterized from the other strains only by a specific repeat region on the CS protein. Results indicated that there is at least one protective B-cell epitope outside the repeat region of the CS protein of P. vivax sporozoites, and that this epitope can be expressed by irradiated sporozoites, rPvCS-1 and -3, but not by rPvCS-1 or NS1(81)V20. Therefore, we designed peptides from the amino acid sequences present both in rPvCS-2 and -3, but not included in the recombinant proteins rPvCS-1 and NS1(81)V20. Anti-peptide antibodies had no activity on the development of sporozoites of P. vivax Salvador I strain, into schizonts in primary culture of Saimiri monkey hepatocytes. In addition, antisporozoite antibodies did not react with any of the peptides. These results suggest that the in vitro inhibition observed in this study could depend upon the conformation of the CS protein. This study also demonstrates that antibody response to unnatural linear epitopes can be induced by immunization with recombinant proteins. 相似文献
2.
Plasmodium vivax malaria vaccine development. 总被引:3,自引:0,他引:3
Plasmodium vivax represents the most widespread malaria parasite worldwide. Although it does not result in as high a mortality rate as P. falciparum, it inflicts debilitating morbidity and consequent economic impact in endemic communities. In addition, the relapsing behavior of this malaria parasite and the recent resistance to anti-malarials contribute to making its control more difficult. Although the biology of P. vivax is different from that of P. falciparum and the human immune response to this parasite species has been rather poorly studied, significant progress is being made to develop a P. vivax-specific vaccine based on the information and experience gained in the search for a P. falciparum vaccine. We have devoted great effort to antigenically characterize the P. vivax CS protein and to test its immunogenicity using the Aotus monkey model. Together with other groups we are also assessing the immunogenicity and protective efficacy of the asexual blood stage vaccine candidates MSP-1 and DBP in the monkey model, as well as the immunogenicity of Pvs25 and Pvs28 ookinete surface proteins. The transmission-blocking efficacy of the responses induced by these latter antigens is being assessed using Anopheles albimanus mosquitoes. The current status of these vaccine candidates and other antigens currently being studied is described. 相似文献
3.
Region II of the malaria circumsporozoite (CS) protein is highly conserved between the CS proteins of different species of malaria. Amino acid sequences homologous to that of region II are found in thrombospondin, properdin, von Willebrand factor and a few other proteins. We show here that the native CS protein from the rodent parasite Plasmodium berghei, and recombinant Plasmodium vivax and Plasmodium falciparum CS proteins containing region II, but not recombinant proteins lacking region II, specifically bind to sulfatides and cholesterol-3-sulfate. The binding is abolished following reduction and alkylation of the proteins. Region II contains 2 cysteines separated by only 3 amino acids, S(N), V, T, and these are the only cysteines present in our recombinant proteins. Therefore, our findings strongly suggest that the region II cysteines are linked by a disulfide bond forming a small peptide loop. We also present evidence that the recognition of sulfatides, cholesterol-3-sulfate, or other cross-reactive sulfated macromolecules by region II may be required during sporozoite invasion of liver cells. Antibodies to a peptide representing region II react with live sporozoites and with sporozoites fixed with glutaraldehyde, indicating that this region is exposed on the surface of the parasites. Furthermore, we have found that the sulfatide and cholesterol-3-sulfate recognition by the CS proteins, and the invasion of hepatocytes by P. berghei sporozoites, are specifically inhibited by dextran sulfate. 相似文献
4.
A novel chimeric Plasmodium vivax circumsporozoite protein induces biologically functional antibodies that recognize both VK210 and VK247 sporozoites
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Yadava A Sattabongkot J Washington MA Ware LA Majam V Zheng H Kumar S Ockenhouse CF 《Infection and immunity》2007,75(3):1177-1185
A successful vaccine against Plasmodium vivax malaria would significantly improve the health and quality of the lives of more than 1 billion people around the world. A subunit vaccine is the only option in the absence of long-term culture of P. vivax parasites. The circumsporozoite protein that covers the surface of Plasmodium sporozoites is one of the best-studied malarial antigens and the most promising vaccine in clinical trials. We report here the development of a novel "immunologically optimal" recombinant vaccine expressed in Escherichia coli that encodes a chimeric CS protein encompassing repeats from the two major alleles, VK210 and VK247. This molecule is widely recognized by sera from patients naturally exposed to P. vivax infection and induces a highly potent immune response in genetically disparate strains of mice. Antibodies from immunized animals recognize both VK210 and VK247 sporozoites. Furthermore, these antibodies appear to be protective in nature since they cause the agglutination of live sporozoites, an in vitro surrogate of sporozoite infectivity. These results strongly suggest that recombinant CS is biologically active and highly immunogenic across major histocompatibility complex strains and raises the prospect that in humans this vaccine may induce protective immune responses. 相似文献
5.
Polymorphism in the circumsporozoite protein of the human malaria parasite Plasmodium vivax. 总被引:4,自引:0,他引:4
S H Qari I F Goldman M M Povoa S di Santi M P Alpers A A Lal 《Molecular and biochemical parasitology》1992,55(1-2):105-113
The circumsporozoite (CS) protein that covers the surface of infectious sporozoites is a candidate antigen in malaria vaccine development. To determine the extent of B- and T-epitope polymorphism and to understand the mechanisms of antigenic variability, we have characterized the CS protein gene of Plasmodium vivax from field isolates representing geographically distant regions of Papua New Guinea (PNG) and Brazil. In the central repeat region of the CS protein, in addition to variation in the number of repeats, an array of mutations was observed which suggests that point mutations have led to the emergence of the variant CS repeat sequence ANGA(G/D)(N/D)QPG from GDRA(D/A)GQPA. Outside the repeat region of the protein, the nonsilent nucleotide substitutions of independent origin are localized in three domains of the protein that either harbor known T-cell determinants or are analogous to the Plasmodium falciparum immunodominant determinants, Th2R and Th3R. We have found that, with the exception of one CS clone sequence that was shared by one P. vivax isolate each from PNG and Brazil, the P. vivax CS protein types can be grouped into Papuan and Brazilian types. These results suggest that an in-depth study of parasite population dynamics is required before field trials for vaccine formulation based on polymorphic immunodominant determinants are conducted. 相似文献
6.
G Del Giudice C Tougne J A Louis P H Lambert E Bianchi F Bonelli L Chiappinelli A Pessi 《European journal of immunology》1990,20(7):1619-1622
The major repetitive epitopes of the surface circumsporozoite (CS) protein of malaria sporozoites represent candidates for the development of subunit vaccines against malaria. However, previous experimental work has shown that repetitive peptides from the CS proteins of Plasmodium falciparum, P. vivax, P. yoelii and P. berghei are immunogenic only in mice with the H-2b or H-2k haplotype. This led to the conclusion that strong T helper epitopes from the non-repetitive CS sequences were required in the design of sporozoite vaccines. In the present study, we investigated the immunogenicity in mice of a octa-branched multiple antigen peptide (MAP) containing repeats of the CS protein of the human malaria parasite, P. malariae, [MAP8(NAAG)6], and found that mice with an H-2b, H-2d, H-2k, H-2f, H-2q, and H-2s haplotype produced anti-peptide antibodies after immunization and that only H-2r mice were nonresponsive. This antibody response, not induced in athymic H-2b nu/nu mice, was directed against the (NAAG) sequence, but not against the lysine core of the MAP construct. Finally, when covalently linked to a synthetic polymer of the repetitive (NANP) sequence of the P. falciparum CS protein, [MAP8(NAAG)6] behaved as a carrier molecule for the production of anti-(NANP)n antibodies in H-2d and H-2k mice, genetically nonresponder to the (NANP)n sequence. Should this wide immunogenicity of the P. malariae CS (NAAG) repetitive sequence also apply to humans, it might be considered for the design of multivalent subunit malaria vaccines. 相似文献
7.
Differentiation antigens on rhesus monkey lymphocytes. I. Identification of T cells bearing CD3 and CD8, and of a subset of CD8-bearing cells 总被引:4,自引:0,他引:4
F J Nooij J G Borst G J Van Meurs M Jonker H Balner 《European journal of immunology》1986,16(8):975-979
Rhesus monkeys provide an excellent preclinical model to test the effect of monoclonal antibodies (mAb) in vitro and in vivo. So far, mostly mAb have been used which were originally raised against human cell surface antigens but cross-reacted reasonably well with homologous antigens on rhesus monkey cells. However, to optimize the model, it was necessary to produce mAb which react specifically with subsets of rhesus monkey lymphocytes. In this report, three mouse anti-rhesus monkey mAb are described, specific for different subsets of rhesus monkey T lymphocytes. None of the reagents cross-reacts with human lymphocytes. Characterization of these mAb was based upon indirect immunofluorescence, using a simultaneous staining technique, and immunoprecipitation of the specific target antigens. One antibody (GM9) reacts with the same subset as is recognized by mAb specific for human CD8+ cells. The second mAb (GM13) is specific for a subset of CD8+ cells. A third mAb (FN18) was of particular interest: it identifies a cell surface complex, RhT3, expressed on mature T lymphocytes, of which the polypeptide chains have a molecular mass of 22 and 27 kDa. The data strongly suggest that RhT3 is a CD3-like determinant, so far unidentified in the rhesus monkey. 相似文献
8.
The observation that protective immunity induced by immunization with radiation attenuated Plasmodium berghei and Plasmodium yoelii sporozoites is dependent on CD8+ T lymphocytes in some strains of mice led us to speculate that immunization with sporozoites induces cytotoxic T lymphocytes (CTL) that recognize malaria antigens on the surface of malaria-infected hepatocytes. In this report we summarize a series of experiments that confirm this hypothesis. We first showed that when immune mice are challenged with live sporozoites they develop malaria-specific, CD8+ T cell-dependent infiltrates in their livers. Next we demonstrated that spleen cells from immune mice eliminate malaria infected hepatocytes from in vitro culture in an antigen specific and genetically restricted manner, indicating that these immune cells recognize malaria antigens on the surface of infected hepatocytes. Finally we defined a CTL epitope of the P. yoelii CS protein, and demonstrated that CTL against this 16-amino-acid peptide (PYCTL1) eliminate infected hepatocytes from culture in an antigenic specific, and MHC restricted manner, indicating that this 16-amino-acid peptide from the CS protein is present on the surface of the infected hepatocytes. We are currently working on constructing vaccines that induce protective CTL against PYCTL1, and identifying additional pre-erythrocytic stage targets of CTL mediated protective immunity. 相似文献
9.
Differential antibody responses to Plasmodium falciparum and P. vivax circumsporozoite proteins in a human population. 总被引:2,自引:0,他引:2
T R Burkot P M Graves R A Wirtz B J Brabin D Battistutta J A Cattani R M Maizels M P Alpers 《Journal of clinical microbiology》1989,27(6):1346-1351
Papua New Guineans exposed to hyperendemic malaria in the Madang area showed different antibody responses to Plasmodium falciparum and Plasmodium vivax sporozoites despite comparable entomological inoculation rates. Although there was a significant trend of increasing prevalence of anti-P. falciparum circumsporozoite (CS) protein immunoglobulin G (IgG) with age, there was no significant increase in the antibody units of IgG recognizing P. falciparum CS proteins. Antibodies recognizing P. vivax CS proteins steadily increased in prevalence and antibody units with age. Significant trends of increasing prevalence of antibody responders (both IgG and IgM) with increasing splenic enlargement were found in the younger age groups for P. falciparum CS proteins but not for P. vivax CS proteins. When antibody responders were analyzed by quartiles, there was a trend of increasing antibody response with age against P. vivax CS peptide, but not for P. falciparum CS protein. There was no evidence for increasing protection against blood-stage infections with increasing antibody levels for either P. falciparum or P. vivax. Neither were any significant relationships found between entomological inoculation rates and either CS antibody prevalence or concentration among the villages studied. 相似文献
10.
Development and evaluation of an immunochromatographic kit for the detection of antibody to Plasmodium vivax infection in South Korea 总被引:5,自引:0,他引:5
Park SK Lee KW Hong SH Kim DS Lee JH Jeon BH Kim WS Shin HJ An SH Park H 《Yonsei medical journal》2003,44(4):747-750
Malaria is a major parasitic disease in tropical areas. Three to five hundred million people suffer from the disease and it kill a million people per year. Blood smear observation was developed for the diagnosis of malaria, but the examination needs skilled experts and exact diagnosis is time consuming. A kit based on immunochromatography can be a reliable and rapid method for clinical diagnosis, even in the hands of inexperienced personnel. However, all such currently developed kits can only diagnose P. falciparum malaria. In our previous report, the C-terminal region of P. vivax merozoite surface protein 1 (PvcMSP) was cloned and expressed in E. coli. In the present study, we developed an immunochromatographic kit using this PvcMSP for the diagnosis of specific antibody to P. vivax malaria in serum samples. The kit was used to examine sera from vivax malaria patients and non-malaria- infected person and the test showed 100% sensitivity (78/78) and 98.3% specificity (58/59). This result demonstrated that the immunochromatographic kit for P. vivax antibody detection is applicable for the rapid and precise diagnosis of P. vivax malaria. 相似文献
11.
Kumar KA Oliveira GA Edelman R Nardin E Nussenzweig V 《Journal of immunological methods》2004,292(1-2):157-164
The circumsporozoite (CS) protein is the major surface protein of Plasmodium sporozoites. Antibodies to the immunodominant repeat domain of CS immobilize sporozoites and prevent infection of hepatocytes. Plasmodium falciparum vaccines containing CS repeats are undergoing human trials in endemic areas, and proof of efficacy has been obtained. The correlates of protection are under investigation. Levels of anti-repeat antibodies in the serum of the human volunteers have been measured mostly by enzyme-linked immunosorbent assay (ELISA) and IFA. Assays that measure the effect of the serum antibodies on parasite infectivity (serum neutralization assays SNAs) are not usually performed because they require a susceptible host and P. falciparum sporozoites are highly infectious only to humans. To overcome this limitation, we developed a new assay named transgenic sporozoite neutralization assay (TSNA) that uses as neutralization target, a transgenic rodent malaria parasite Plasmodium berghei that bears the P. falciparum CS repeats [CS(Pf)]. Following incubation with human serum, CS(Pf) infectivity of HepG2 cells is evaluated by real-time PCR. We have compared ELISA titers and TSNAs in a limited number of sera from humans immunized with (T1B)4 MAP, a peptide vaccine containing P. falciparum CS repeats. A comparison between the two assays did not reach significance (p=0.175) when analyzed by non-parametric Spearman correlation method. Ongoing human trials of CS-based vaccines should provide an opportunity to determine whether TSNAs will provide better correlates of protective immunity than ELISA assays. 相似文献
12.
We studied the interaction of sera from residents of an area in northern Peru where vivax malaria is endemic with four recombinant DNA-derived circumsporozoite (CS) proteins of Plasmodium vivax. The antigens used in the enzyme-linked immunosorbent assay included one Escherichia coli-produced and three Saccharomyces cerevisiae-produced recombinant proteins. Three of the proteins (NS1(81)V20, Vivax-1, and Vivax-2) contain the entire central repeat region of the P. vivax CS protein, and one protein (Vivax-3) contains only two repeat sequences. Vivax-1, Vivax-2, and Vivax-3 contain different lengths of sequences flanking the repeats. A higher percentage of the sera had antibodies to Vivax-2 and Vivax-3, the two proteins containing the longest nonrepeat sequences, than to NS1(81)V20 or Vivax-1. Children less than 5 years of age did not have immunoglobulin G antibodies to NS1(81)V20; however, they had antibodies to Vivax-1, Vivax-2, and Vivax-3. The finding that individuals living in a malaria-endemic area produce antibodies to peptides containing nonrepeat regions of the CS protein emphasizes the need to characterize the immune response to these regions in naturally exposed and experimentally immunized humans. 相似文献
13.
Kim TS Kim HH Lee SS Oh CM Choi KM Lin K Kim JY Na BK Han ET Sohn Y Kim H Lee HW 《Parasitology research》2011,108(5):1275-1282
Plasmodium vivax is classified into two serotypes, VK210 [the dominant form-GDRA(D/A)GQPA repeats] and VK247 [the variant form-ANGA(G/D)(N/D)QPG repeats], based on sequence variation of the repeat region of the circumsporozoite (CS) protein gene. Genomic DNA for the variant CS protein gene was obtained from field isolate strains in Myanmar. The repetitive region has highly 19 immunogenic repeats flanked by non-repeat stretches of amino acids. The sequence including this region (717 bp) was subcloned into the expression vector pQE30 and expressed in Escherichia coli. The expressed recombinant protein has a molecular weight of about 50 kDa as analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) analysis. Anti-VK247 antibodies were found in malaria patients who have been exposed to variant form of P. vivax in western blot analysis. Therefore, this recombinant protein might be a useful tool in serodiagnosis of malaria patients who have been infected with variant form of P. vivax. 相似文献
14.
A reduced risk of infection with Plasmodium vivax and clinical protection against malaria are associated with antibodies against the N terminus but not the C terminus of merozoite surface protein 1
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Nogueira PA Alves FP Fernandez-Becerra C Pein O Santos NR Pereira da Silva LH Camargo EP del Portillo HA 《Infection and immunity》2006,74(5):2726-2733
Progress towards the development of a malaria vaccine against Plasmodium vivax, the most widely distributed human malaria parasite, will require a better understanding of the immune responses that confer clinical protection to patients in regions where malaria is endemic. The occurrence of clinical protection in P. vivax malaria in Brazil was first reported among residents of the riverine community of Portuchuelo, in Rond?nia, western Amazon. We thus analyzed immune sera from this same human population to determine if naturally acquired humoral immune responses against the merozoite surface protein 1 of P. vivax, PvMSP1, could be associated with reduced risk of infection and/or clinical protection. Our results demonstrated that this association could be established with anti-PvMSP1 antibodies predominantly of the immunoglobulin G3 subclass directed against the N terminus but not against the C terminus, in spite of the latter being more immunogenic and capable of natural boosting. This is the first report of a prospective study of P. vivax malaria demonstrating an association of reduced risk of infection and clinical protection with antibodies against an antigen of this parasite. 相似文献
15.
G Del Giudice C Tougne L Renia T Ponnudurai G Corradin A Pessi A S Verdini J A Louis D Mazier P H Lambert 《Molecular immunology》1991,28(9):1003-1009
Monoclonal antibodies (mAbs) were raised in mice against the synthetic peptide (NANP)40, consisting of 40 (NANP) repeats of the circumsporozoite (CS) protein of the human malaria parasite, Plasmodium falciparum, and characterized. (i) Five of these mAbs recognized the P. falciparum CS protein in western blot experiments and in immunofluorescence assays using different preparations of sporozoites. The remaining two mAbs (CT3.2 and CT3.3, both IgG1) gave negative results by both techniques. (ii) When the anti-(NANP)40 peptide mAbs were functionally tested in vitro to assess their ability to inhibit the attachment and penetration of the parasites into cultured human liver cells, six of them exhibited inhibitory activities ranging between 66 and 90%. CT3.2 mAbs, also, inhibited sporozoite attachment and penetration, despite the negative results by immunofluorescence and western blot experiments. However, when immunofluorescence was repeated in the presence of calcium, CT3.2 did reveal a positive recognition of P. falciparum sporozoites, suggesting that this mAb could recognize the (NANP) sequence when calcium was bound to the repetitive peptide. (iii) Furthermore, the binding of an anti-(NANP)40 IgM mAb (CT1) to the solid-phase peptide was not inhibited by preincubation of the peptide with a mAb against the P. falciparum CS protein. (iv) Finally, one anti-(NANP)40 IgG1 mAb (CT3.1) was unable to bind to the shorter (NANP)3 peptide, although it recognized the (NANP)40 peptide and the P. falciparum CS protein. The results presented here suggest that heterogeneous antibody populations are produced upon immunization of mice with (NANP)40 synthetic peptide and that epitopes different from those simply related to the linear (NANP) amino acid sequence are likely to be present in long (NANP)n constructs as well as in the repetitive domain of the P. falciparum CS protein. 相似文献
16.
Plasmodium vivax promiscuous T-helper epitopes defined and evaluated as linear peptide chimera immunogens 总被引:4,自引:0,他引:4
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Caro-Aguilar I Rodríguez A Calvo-Calle JM Guzmán F De la Vega P Patarroyo ME Galinski MR Moreno A 《Infection and immunity》2002,70(7):3479-3492
Clinical trials of malaria vaccines have confirmed that parasite-derived T-cell epitopes are required to elicit consistent and long-lasting immune responses. We report here the identification and functional characterization of six T-cell epitopes that are present in the merozoite surface protein-1 of Plasmodium vivax (PvMSP-1) and bind promiscuously to four different HLA-DRB1* alleles. Each of these peptides induced lymphoproliferative responses in cells from individuals with previous P. vivax infections. Furthermore, linear-peptide chimeras containing the promiscuous PvMSP-1 T-cell epitopes, synthesized in tandem with the Plasmodium falciparum immunodominant circumsporozoite protein (CSP) B-cell epitope, induced high specific antibody titers, cytokine production, long-lasting immune responses, and immunoglobulin G isotype class switching in BALB/c mice. A linear-peptide chimera containing an allele-restricted P. falciparum T-cell epitope with the CSP B-cell epitope was not effective. Two out of the six promiscuous T-cell epitopes exhibiting the highest anti-peptide response also contain B-cell epitopes. Antisera generated against these B-cell epitopes recognize P. vivax merozoites in immunofluorescence assays. Importantly, the anti-peptide antibodies generated to the CSP B-cell epitope inhibited the invasion of P. falciparum sporozoites into human hepatocytes. These data and the simplicity of design of the chimeric constructs highlight the potential of multimeric, multistage, and multispecies linear-peptide chimeras containing parasite promiscuous T-cell epitopes for malaria vaccine development. 相似文献
17.
E H Nardin P J Barr H L Gibson W E Collins R S Nussenzweig V Nussenzweig 《European journal of immunology》1987,17(12):1763-1767
A recombinant Plasmodium vivax circumsporozoite (CS) protein (rPvCS-1) has been investigated as a possible malaria sporozoite vaccine candidate. Experiments were carried out to determine whether sporozoite-specific memory cells develop in Swiss Webster mice immunized with rPvCS-1. Challenge of rPvCS-1-immunized mice with P. vivax sporozoites resulted in a 100-fold increase in the mean serum anti-sporozoite antibody titer. The presence of parasite-specific T helper cells was demonstrated using an in vitro assay. Anti-CS antibodies were detected in the culture supernatants of spleen cells of rPvCS-1-immunized mice following in vitro challenge with P. vivax sporozoite extract. Immune spleen cells depleted of T cells did not produce antibodies when challenged with sporozoite extract in vitro. In conclusion, immunization of mice with the rPvCS-1 protein induced memory T cells which recognized native CS antigen and functioned as T helper cells in the production of anti-sporozoite antibodies both in vivo and in vitro. 相似文献
18.
Arthur E. Brown H. Kyle Webster Somchit Tulyayon Anintita Suvarnamani Robert A. Wirtz Prasit Sookto 《Journal of clinical immunology》1988,8(5):342-348
The circumsporozoite (CS) protein on the surface of sporozoites is the major target for antibody response(s) to the infective stage of the malaria parasite. Sera from malaria endemic areas contain both IgM and IgG antibodies that react with a dominant epitope in the tetrapeptide repeat region of the CS protein. In order to characterize the IgM CS antibody response inPlasmodium falciparum (PF) malaria, a prospective study was conducted in Thai Rangers. Variable IgM responses against the CS protein were detected in 81% of 47 PF-infected subjects. Similar to IgG response kinetics, IgM levels rose to a peak 6–10 days after detection of parasitemia and showed an apparent serum half-life of less than 25 days. The classic difference in isotype ratio (IgG/IgM) between primary and secondary antibody responses was observed to bloodstage, but not CS, antigens. 相似文献
19.
Naturally acquired and vaccine-elicited antibodies block erythrocyte cytoadherence of the Plasmodium vivax Duffy binding protein 总被引:4,自引:0,他引:4
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Malaria merozoites require the presence of specific surface receptors on the red blood cell for invasion. Plasmodium vivax, requires the Duffy blood group antigen as an obligate receptor for invasion. The parasite Duffy binding protein (DBP) is the ligand involved in this process, making the DBP a potential vaccine candidate. A preliminary objective was to study whether people exposed to vivax malaria acquire antibodies that have the ability to block erythrocyte cytoadherence to the PvDBP. In comparison, we studied the immunogenicity of various recombinant DBP vaccines and investigated their potential to induct antifunctional antibodies. In order to do so, recombinant proteins to different regions of the putative ectodomain of the DBP and a DNA vaccine were used to immunize laboratory animals. An in vitro cytoadherence assay was used to investigate the presence of antifunctional antibodies in plasmas from people naturally exposed to vivax malaria, as well as in antisera obtained by animal vaccination. Our results showed that human plasma from populations naturally exposed to vivax malaria, as well as antisera obtained by vaccination using recombinant proteins, a DNA vaccine, and a synthetic peptide to DBP, inhibited in vitro binding of human erythrocytes to the DBP ligand domain (DBP(II)) in correlation to their previously measured antibody titer. Our results provide further evidence for the vaccine potential of this essential parasite adhesion molecule. 相似文献
20.
Lumsden JM Pichyangkul S Srichairatanakul U Yongvanitchit K Limsalakpetch A Nurmukhambetova S Klein J Bertholet S Vedvick TS Reed SG Sattabongkot J Bennett JW Polhemus ME Ockenhouse CF Howard RF Yadava A 《Infection and immunity》2011,79(9):3492-3500
Plasmodium vivax is the major cause of malaria outside sub-Saharan Africa and inflicts debilitating morbidity and consequent economic impacts in developing countries. In order to produce a P. vivax vaccine for global use, we have previously reported the development of a novel chimeric recombinant protein, VMP001, based on the circumsporozoite protein (CSP) of P. vivax. Very few adjuvant formulations are currently available for human use. Our interest is to evaluate second-generation vaccine formulations to identify novel combinations of adjuvants capable of inducing strong, long-lasting immune responses. In this study rhesus monkeys were immunized intramuscularly three times with VMP001 in combination with a stable emulsion (SE) or a synthetic Toll-like receptor 4 (TLR4) agonist (glucopyranosyl lipid A [GLA]) in SE (GLA-SE). Sera and peripheral blood mononuclear cells (PBMCs) were tested for the presence of antigen-specific humoral and cellular responses, respectively. All groups of monkeys generated high titers of anti-P. vivax IgG antibodies, as detected by enzyme-linked immunosorbent assays (ELISAs) and immunofluorescence assays. In addition, all groups generated a cellular immune response characterized by antigen-specific CD4(+) T cells secreting predominantly interleukin-2 (IL-2) and lesser amounts of tumor necrosis factor (TNF). We conclude that the combination of VMP001 and GLA-SE is safe and immunogenic in monkeys and may serve as a potential second-generation vaccine candidate against P. vivax malaria. 相似文献