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PubMed1994

Immunologic cross-reactivity between structural proteins of human T-cell lymphotropic virus type I and the blood stage of Plasmodium falciparum.

To determine the serologic cross-reactivity between human T-cell lymphotropic virus type I (HTLV-I) and parasite antigens, we measured antibody responses against HTLV-I, Plasmodium falciparum, Plasmodium vivax, and Brugia malayi in serum specimens obtained from regions where malaria (n = 482) and filariasis (n = 101) are endemic. Analysis of immune reactivity to HTLV-I antigens showed that specimens from regions where malaria is endemic had significantly higher rates of enzyme immunoassay (EIA) reactivity (76 of 482 [15.8%] than those from regions where filariasis is endemic (0 of 101 [0%]). Western blot (immunoblot) analysis of the HTLV-I EIA-reactive specimens demonstrated predominant Gag reactivity (HTLV-Iind). Only two specimens each from Indonesia and Brazil and four specimens from Papua New Guinea had Env reactivity by radioimmunoprecipitation analysis. Furthermore, a positive correlation between HTLV-EIA and titers of antibody to the blood stage of P. falciparum (rs = 0.24, P < 0.005) was discerned; no correlation was observed between antibodies to the blood stage or the circumsporozoite protein of P. vivax and the circumsporozoite protein of P. falciparum. In addition, P. falciparum-infected erythrocyte lysate specifically abrogated binding of Gag-specific antibodies in HTLV-Iind specimens from regions where malaria is endemic without affecting binding in HTLV-I-seropositive specimens, suggesting that the immunologic cross-reactivity between HTLV Gag proteins and malaria parasites is restricted to the blood-stage antigens of plasmodia in specimens from regions where malaria is endemic. However, HTLV-seroindeterminate specimens from the United States did not demonstrate serologic cross-reactivity, suggesting that antigenic mimicry of HTLV proteins extends to other nonplasmodial antigens as well.

Animals↗
PubMed2005

Plasmodium ovale: parasite and disease.

Humans are infected by four recognized species of malaria parasites. The last of these to be recognized and described is Plasmodium ovale. Like the other malaria parasites of primates, this parasite is only transmitted via the bites of infected Anopheles mosquitoes. The prepatent period in the human ranges from 12 to 20 days. Some forms in the liver have delayed development, and relapse may occur after periods of up to 4 years after infection. The developmental cycle in the blood lasts approximately 49 h. An examination of records from induced infections indicated that there were an average of 10.3 fever episodes of > or = 101 degrees F and 4.5 fever episodes of > or = 104 degrees F. Mean maximum parasite levels were 6,944/microl for sporozoite-induced infections and 7,310/microl for trophozoite-induced infections. Exoerythrocytic stages have been demonstrated in the liver of humans, chimpanzees, and Saimiri monkeys following injection of sporozoites. Many different Anopheles species have been shown to be susceptible to infection with P. ovale, including A. gambiae, A. atroparvus, A. dirus, A. freeborni, A. albimanus, A. quadrimaculatus, A. stephensi, A. maculatus, A. subpictus, and A. farauti. An enzyme-linked immunosorbent assay has been developed to detect mosquitoes infected with P. ovale using a monoclonal antibody directed against the circumsporozoite protein. Plasmodium ovale is primarily distributed throughout sub-Saharan Africa. It has also been reported from numerous islands in the western Pacific. In more recent years, there have been reports of its distribution on the Asian mainland. Whether or not it will become a major public health problem there remains to be seen. The diagnosis of P. ovale is based primarily on the characteristics of the blood stages and its differentiation from P. vivax. The sometimes elliptical shape of the infected erythrocyte is often diagnostic when combined with other, subtler differences in morphology. The advent of molecular techniques, primarily PCR, has made diagnostic confirmation possible. The development of techniques for the long-term frozen preservation of malaria parasites has allowed the development diagnostic reference standards for P. ovale. Infections in chimpanzees are used to provide reference and diagnostic material for serologic and molecular studies because this parasite has not been shown to develop in other nonhuman primates, nor has it adapted to in vitro culture. There is no evidence to suggest that P. ovale is closely related phylogenetically to any other of the primate malaria parasites that have been examined.

Animals↗
PubMed2006

Plasmodium falciparum AMA1 binds a rhoptry neck protein homologous to TgRON4, a component of the moving junction in Toxoplasma gondii.

Plasmodium falciparum apical membrane antigen 1 (PfAMA1) coimmunoprecipitates with the Plasmodium homologue of TgRON4, a secreted rhoptry neck protein of Toxoplasma gondii that migrates at the moving junction in association with TgAMA1 during invasion. PfRON4 also originates in the rhoptry necks, suggesting that this unusual collaboration of micronemes and rhoptries is a conserved feature of Apicomplexa.

Animals↗
PubMed2002

A multigene family that interacts with the amino terminus of plasmodium MSP-1 identified using the yeast two-hybrid system.

Merozoite surface protein 1 (MSP-1) is a high-molecular-weight protein expressed on the surface of the malaria merozoite in a noncovalent complex with other protein molecules. MSP-1 undergoes a series of proteolytic processing events, but no precise biological role for the various proteolytic fragments of MSP-1 or for the additional proteins present in the complex is known. Through the use of the yeast two-hybrid system, we have isolated genes encoding proteins that interact with a region of the amino-terminal proteolytic fragment of MSP-1 from the mouse parasite Plasmodium yoelii. This analysis has led to the isolation of two sequence-related molecules, one of which is the P. yoelii homologue of MSP-7 originally described in Plasmodium falciparum. BLAST analysis of the P. falciparum database has revealed that there are six related protein molecules present in this species encoded near each other on chromosome 13. In P. falciparum, we designated these molecules MSRP-1 to -5. Analysis of the P. yoelii database indicates a similar chromosomal organization for the two genes in the mouse parasite species. The three P. falciparum sequences with the highest degree of homology to the P. yoelii sequences isolated in the two-hybrid screen have been characterized at the molecular level (MSRP-1 to -3). Expression analysis indicated that the mRNAs are expressed at various levels in the different asexual stages. Immunofluorescence studies colocalized the expression of the MSRP molecules and the amino-terminal portion of MSP-1 to the surfaces of trophozoites. In vitro binding experiments confirmed the interaction between MSRP-1, MSRP-2, and the amino-terminal region of P. falciparum MSP-1.

Amino Acid Sequence↗
PubMed2004

Plasmodium falciparum histone acetyltransferase, a yeast GCN5 homologue involved in chromatin remodeling.

The yeast transcriptional coactivator GCN5 (yGCN5), a histone acetyltransferase (HAT), is part of large multimeric complexes that are required for chromatin remodeling and transcriptional activation. Like other eukaryotes, the malaria parasite DNA is organized into nucleosomes and the genome encodes components of chromatin-remodeling complexes. Here we show that GCN5 is conserved in Plasmodium species and that the most homologous regions are within the HAT domain and the bromodomain. The Plasmodium falciparum GCN5 homologue (PfGCN5) is spliced with three introns, encoding a protein of 1,464 residues. Mapping of the ends of the PfGCN5 transcript suggests that the mRNA is 5.2 to 5.4 kb, consistent with the result from Northern analysis. Using free core histones, we determined that recombinant PfGCN5 proteins have conserved HAT activity with a substrate preference for histone H3. Using substrate-specific antibodies, we determined that both Lys-8 and -14 of H3 were acetylated by the recombinant PfGCN5. In eukaryotes, GCN5 homologues interact with yeast ADA2 homologues and form large multiprotein HAT complexes. We have identified an ADA2 homologue in P. falciparum, PfADA2. Yeast two-hybrid and in vitro binding assays verified the interactions between PfGCN5 and PfADA2, suggesting that they may be associated with each other in vivo. The conserved function of the HAT domain in PfGCN5 was further illustrated with yeast complementation experiments, which showed that the PfGCN5 region corresponding to the full-length yGCN5 could partially complement the yGCN5 deletion mutation. Furthermore, a chimera comprising the PfGCN5 HAT domain fused to the remainder of yeast GCN5 (yGCN5) fully rescued the yGCN5 deletion mutant. These data demonstrate that PfGCN5 is an authentic GCN5 family member and may exist in chromatin-remodeling complexes to regulate gene expression in P. falciparum.

Acetyltransferases↗
PubMed2006

A linear peptide containing minimal T- and B-cell epitopes of Plasmodium falciparum circumsporozoite protein elicits protection against transgenic sporozoite challenge.

An effective malaria vaccine is needed to address the public health tragedy resulting from the high levels of morbidity and mortality caused by Plasmodium parasites. The first protective immune mechanism identified in the irradiated sporozoite vaccine, the "gold standard" for malaria preerythrocytic vaccines, was sporozoite-neutralizing antibody specific for the repeat region of the surface circumsporozoite (CS) protein. Previous phase I studies demonstrated that a branched peptide containing minimal T- and B-cell epitopes of Plasmodium falciparum CS protein elicited antirepeat antibody and CD4(+)-T-cell responses comparable to those observed in volunteers immunized with irradiated P. falciparum sporozoites. The current study compares the immunogenicity of linear versus tetrabranched peptides containing the same minimal T- and B-cell epitopes, T1BT*, comprised of a CS-derived universal Th epitope (T*) synthesized in tandem with the T1 and B repeats of P. falciparum CS protein. A simple 48-mer linear synthetic peptide was found to elicit antisporozoite antibody and gamma interferon-secreting T-cell responses comparable to the more complex tetrabranched peptides in inbred strains of mice. The linear peptide was also immunogenic in outbred nonhuman primates (Aotus nancymaae), eliciting antibody titers equivalent to those induced by tetrabranched peptides. Importantly, the 48-mer linear peptide administered in adjuvants suitable for human use elicited antibody-mediated protection against challenge with rodent malaria transgenic sporozoites expressing P. falciparum CS repeats. These findings support further evaluation of linear peptides as economical, safe, and readily produced malaria vaccines for the one-third of the world's population at risk of malaria infection.

Amino Acid Sequence↗
PubMed2006

A novel chimeric Plasmodium vivax circumsporozoite protein induces biologically functional antibodies that recognize both VK210 and VK247 sporozoites.

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.

Animals↗
PubMed2006

Immunity to recombinant plasmodium falciparum merozoite surface protein 1 (MSP1): protection in Aotus nancymai monkeys strongly correlates with anti-MSP1 antibody titer and in vitro parasite-inhibitory activity.

A number of malarial blood-stage candidate vaccines are currently being tested in human clinical trials, but our understanding of the relationship between clinical immunity and data obtained from in vitro assays remains inadequate. An in vitro assay which could reliably predict protective immunity in vivo would facilitate vaccine development. Merozoite surface protein1 (MSP1) is a leading blood-stage malaria vaccine candidate, and anti-MSP1 antibodies from individuals that are clinically immune to malaria inhibit the invasion of Plasmodium merozoites into erythrocytes in vitro. Using expression in Escherichia coli and subsequent refolding, we have produced two allelic forms of MSP1(42) (FVO and 3D7). Aotus nancymai monkeys were immunized with MSP1(42)-FVO, MSP1(42)-3D7, or a combination of FVO and 3D7 allelic forms, (MSP1(42)-C1) and were subsequently challenged with Plasmodium falciparum FVO parasites. Sera obtained prior to challenge were tested by standardized enzyme-linked immunosorbent assay (ELISA) to determine antibody titer, and immunoglobulin G (IgG) fractions were also obtained from the same sera; the IgG fractions were tested in an in vitro growth inhibition (GI) assay to evaluate biological activity of the antibodies. Regardless of the immunogen used, all monkeys that had >200,000 ELISA units against MSP1(42)-FVO antigen before challenge controlled their infections. By contrast, all monkeys whose purified IgGs gave <60% inhibition activity in an in vitro GI assay with P. falciparum FVO required treatment for high parasitemia after challenge. There is a strong correlation between ELISA units (Spearman rank correlation of greater than 0.75) or GI activity (Spearman rank correlation of greater than 0.70) and protective immunity judged by various parameters (e.g., cumulative parasitemia or day of patency). These data indicate that, in this monkey model, the ELISA and GI assay values can significantly predict protective immunity induced by a blood-stage vaccine, and they support the use of these assays as part of evaluation of human clinical trials of MSP1-based vaccines.

Animals↗
PubMed2006

Differential expression of var gene groups is associated with morbidity caused by Plasmodium falciparum infection in Tanzanian children.

The var gene family of Plasmodium falciparum encodes the variant surface antigen Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1). PfEMP1 is considered an important pathogenicity factor in P. falciparum infection because it mediates cytoadherence to host cell endothelial receptors. var genes can be grouped into three major groups, A, B, and C, and the conserved var genes, var1-4, according to sequence similarities in coding and noncoding upstream regions. Using real-time quantitative PCR in a study conducted in Tanzania, the var transcript abundances of the different var gene groups were compared among patients with severe, uncomplicated, and asymptomatic malaria. Transcripts of var group A and B genes were more abundant in patients with severe malaria than in patients with uncomplicated malaria. In general, the transcript abundances of var group A and B genes were higher for children with clinical malaria than for children with asymptomatic infections. The var group C and var1-like transcript abundances were similar between the three sample groups. A transcript abundance pattern similar to that for var group A was observed for var2csa and var3-like genes. These results suggest that substantial and systematic differences in var gene expression exist between different clinical presentations.

Animals↗
PubMed1974

Immunity to Plasmodium berghei in rats: passive serum transfer and role of the spleen.

Pools of rat antiserum to Plasmodium berghei had different levels of protective activity as assessed by a passive transfer test. Preincubation of parasite inocula with an effective pool before injection did not significantly enhance protective activity. Removal of the antiserum from preincubated parasite inocula abolished the bulk of protective activity. Similarly, antiserum effective in intact animals was largely ineffective in splenectomized recipients. These experiments suggest a minimal role for antibody acting directly on P. berghei-parasitized cells and reemphasize a significant role for the spleen in immunity to this plasmodium.

Animals↗
PubMed1982

Monoclonal antibodies that protect in vivo against Plasmodium chabaudi recognize a 250,000-dalton parasite polypeptide.

Twenty monoclonal antibodies have been prepared to the erythrocytes from CBA/Ca mice infected with the rodent malaria Plasmodium chabaudi. By immunofluorescence, 15 of these antibodies recognized parasite antigens expressed only during the development of mature trophozoites to schizonts and merozoites, 2 recognized parasite antigens that were expressed throughout most of the intraerythrocytic cycle, and 3 recognized the membranes of all infected and uninfected erythrocytes. By immunoprecipitation of [35S]methionine-labeled, parasitized erythrocytes, parasite antigens recognized by all of the antiparasite antibodies were characterized. Eleven precipitated a 250,000-dalton parasite polypeptide which was synthesized and expressed late in the intraerythrocytic cell cycle and which appeared to be the major coat protein of the merozoites. In passive protection experiments, transfer of hyperimmune serum before infection with the parasite resulted in a delay in the rise of parasitemia, reduction in peak parasitemias, and a delay in the clearance of the parasitemia. Two monoclonal antibodies to the 250,000-dalton polypeptide had a similar but not as marked effect on parasitemia when given as a single dose before infection. When mixed and administered throughout the course of infection, their effects were greater. They had no influence on the course of Plasmodium berghei KSP11 parasitemia. Monoclonal antibodies to other parasite antigens and normal erythrocyte antigens failed to have a significant and reproducible effect on P. chabaudi parasitemia. The results suggest that this 250,000-dalton malaria parasite antigen may be important in the induction and expression of antibody-mediated immunity to malaria.

Animals↗
PubMed1987

Glycoprotein recognition mediates attachment of Plasmodium chabaudi to mouse erythrocytes.

The interaction between Plasmodium falciparum merozoites and human erythrocytes is mediated by specific parasite proteins and sialoglycoproteins (SGPs) on the surface of the host cell. To investigate whether a similar mechanism functions in rodent malaria, a series of experiments was performed to identify the proteins involved in the interaction of Plasmodium chabaudi parasites and mouse erythrocytes. Labeled parasite proteins incubated with purified mouse SGP bound specifically to glycoprotein 2.1. Two parasite proteins (72 and 126 kilodaltons [kDa]) were coprecipitated with antibody directed to mouse erythrocyte membrane proteins. The lower band (72 kDa) as well as a band of 105 kDa were also observed to bind to N-acetyl-D-galactosamine affinity columns, suggesting a carbohydrate component in the binding of these parasites to erythrocytes. These experiments indicate that P. chabaudi possesses specific proteins which recognized SGP on the surface of murine erythrocytes in a manner similar to that of the merozoites of P. falciparum. Thus P. chabaudi in mice may provide an in vivo model of the human parasite for testing ways to inhibit merozoite recognition and invasion of host cells.

Animals↗
PubMed1990

Role of gamma interferon during infection with Plasmodium chabaudi chabaudi.

A role has been proposed for inflammatory mediators such as gamma interferon (IFN-gamma) and reactive oxygen intermediates in the control of the blood stages of Plasmodium organisms. It was previously shown that IFN-gamma can be detected in the plasma of mice with a primary infection by Plasmodium chabaudi chabaudi (AS). We found that susceptible and other resistant mouse strains produced IFN-gamma, suggesting that susceptibility is not due to a defect in IFN-gamma production. Administration of IFN-gamma to intact C57BL/6 mice slightly decreased and partially delayed parasitemia, whereas in vivo depletion of IFN-gamma through injection of a "cocktail" of monoclonal antibodies against IFN-gamma exacerbated infection. Since CD4+ T cells are essential for the development of a protective immune response to P. chabaudi chabaudi, we tested whether CD4+ T cells are responsible for IFN-gamma production in vivo and whether exogenous IFN-gamma can replace the protective function of the CD4+ T cells. Mice depleted of CD4+ T cells were unable to produce IFN-gamma, but factors in addition to IFN-gamma may be important in parasite clearance.

Animals↗
PubMed1990

Two soluble antigens of Plasmodium falciparum induce tumor necrosis factor release from macrophages.

The production of cytokines such as tumor necrosis factor (TNF) may contribute to the pathology of malaria. We showed previously that crude preparations of heat-stable exoantigens from parasite cultures induce the release of TNF in vitro and in vivo. When separated from the culture medium by affinity chromatography, in which immune immunoglobulin G was used as ligand, the mixture of exoantigens of Plasmodium falciparum retained the capacity to induce the secretion of TNF, both by human monocytes from Gambian children and by mouse macrophages. Two individual antigens, Ag1 and Ag7, further purified by affinity chromatography and identified by crossed immunoelectrophoresis, also stimulated TNF production by both types of cell but differed in other functional properties. Thus, the activity of Ag7, but not that of Ag1, was inhibited by polymyxin B, and antisera made against boiled exoantigens of the rodent parasite Plasmodium yoelii which blocked the ability of these antigens to induce the production of TNF also inhibited the activity of Ag7 without affecting Ag1. Since the prevalence of antibody against Ag7 in sera from children in endemic areas appears to correlate with the development of immunity against the manifestations of the disease, this antigen may be one cause of pathology, perhaps through its ability to induce the production of TNF. Its serological relationship with rodent exoantigens suggests that it might be a candidate for an anti-disease vaccine which has the advantage that its active moiety is not subject to significant antigen polymorphism.

Adult↗
PubMed1991

Epstein-Barr virus transformation of Saimiri sciureus (squirrel monkey) B cells and generation of a Plasmodium brasilianum-specific monoclonal antibody in P. brasilianum-infected monkeys.

The new-world monkeys Saimiri sciureus (squirrel monkeys) are currently used as a model to test the efficacy of vaccines against human malaria. To improve our knowledge on this model, we tested the susceptibility of S. sciureus B cells to Epstein-Barr virus (EBV) infection. B-lymphoblastoid cell lines were obtained from six of six healthy animals after infection with the B95-8 source of EBV. The frequency distributions of spleen B cells clonally committed to the production of immunoglobulins M and G, as measured by limiting dilution analysis, were from 1 in 179 to 1 in 1,085 and from 1 in 45 to 1 in 60, respectively, in three monkeys naturally infected with Plasmodium brasilianum. In the same three animals, the frequency of spleen B cells committed to the production of P. brasilianum-specific antibody ranged from 1 in 2,211 to 1 in 9,099. One B-lymphoblastoid cell line producing anti-P. brasilianum-specific antibody was cloned twice, and the immunoglobulin G produced was purified. This monoclonal antibody recognized a parasite component of 197 kDa and was specific for Plasmodium malariae and P. brasilianum parasites. These data document that squirrel monkey B cells naturally primed by an infectious agent can be efficiently used to produce monospecific antibodies against the infectious agent.

Animals↗
PubMed1994

Inhibition of in vitro erythropoiesis by soluble mediators in Plasmodium chabaudi AS malaria: lack of a major role for interleukin 1, tumor necrosis factor alpha, and gamma interferon.

By using erythropoietin-dependent proliferation of splenic erythroid cells as an in vitro erythropoiesis model system, we demonstrate that spleen cells from Plasmodium chabaudi AS-infected C57BL/6 mice potently inhibited erythroid cell proliferation. Inhibitory activity was detected in spleen cell conditioned media (SPCM) prepared from infected mice but not from uninfected mice. The inhibitory activity in SPCM was characterized as being heat sensitive, macromolecular, and host derived. The inhibitory activity was not reversed by increasing the erythropoietin concentration and was found to be specific for the late erythroid lineage. Mouse strains, which differ in their resistance to P. chabaudi AS infection, produced and responded to the inhibitory activity to a similar extent. Putative immune mediators, interleukin 1 alpha, interleukin 1 beta, and gamma interferon, were found to be potent inhibitors of erythroid cell proliferation. However, antibody neutralization experiments failed to demonstrate a major role for these cytokines in the inhibitory activity of SPCM. Our results suggest that the elaboration of inhibitor(s) of erythropoiesis in hemopoietic organs of Plasmodium-infected mice may impair erythroid regeneration. The identity of the inhibitory mediator(s) is presently unknown but is distinct from interleukin 1, tumor necrosis factor alpha, and gamma interferon.

Anemia↗
PubMed1994

Novel proteins of Plasmodium falciparum identified by differential immunoscreening using immune and patient sera.

A differential serological screen of a lambda gt11 cDNA expression library of Plasmodium falciparum was performed in an attempt to identify novel and putative host-protective antigens of the parasite. The screening was done with two categories of sera: (i) acute-phase sera obtained from smear-positive acutely infected P. falciparum patients from various regions in India and (ii) immune sera taken from healthy, permanent adult residents of P. falciparum-endemic rural districts of Orissa in eastern India. These adults had not suffered from any clinical malarial symptoms for at least the previous 3 years at the time of serum collection. Sixty-five clones obtained by screening the lambda gt11 library with two immune serum samples were analyzed extensively with a total of 70 acutely infected patient serum samples. Eight of these clones failed to react with any of the patient sera. Each of these eight clones, when tested individually with 92 serum samples from the immune group, reacted with a minimum of 43% of the samples from this category of sera. Thus, these eight epitopes may encode host-protective elements since they are not recognized by antibodies in the patient sera but react exclusively and extensively with the clinically immune set. Sequence analysis of two of these clones reveals that they are novel Plasmodium genes.

Adult↗
PubMed1996

Dominance of conserved B-cell epitopes of the Plasmodium falciparum merozoite surface protein, MSP1, in blood-stage infections of naive Aotus monkeys.

We have shown that conserved B epitopes were immunodominant in animals hyperimmunized with parasite-purified or recombinant merozoite surface protein MSP1 of Plasmodium falciparum. Cross-priming studies also suggested that a conserved T-helper epitope(s) is efficient in inducing the anti-MSP1 antibody response. In this study, we determined whether a similar profile of immune responses was induced during live P. falciparum infections. Naive Aotus monkeys were infected by blood-stage challenge with either one of the two dimorphic MSP1 alleles represented by the FUP and FVO parasites. Sera collected after parasite clearance were analyzed by enzyme-linked immunosorbent assays (ELISAs). Monkeys infected with parasites carrying one allelic form of MSP1 had antibodies that were equally reactive with homologous or heterologous MSP1s. This preferential recognition of conserved epitopes of MSP1 was confirmed by competitive binding ELISAs. Studies with Plasmodium yoelii and P. falciparum show that the C-terminal 19-kDa fragment of MSP1, MSP1(19), is the target of protective immunity. Thus, monkey sera were assayed for recognition with recombinant MSP1(19)s expressing variant and conserved B epitopes. Results of direct and competitive binding ELISAs showed that the anti-MSP1(19) antibodies were also directed primarily against conserved determinants. The similarities between vaccine- or infection-induced antibody responses suggest a possible reciprocal enhancement of the two populations of anti-MSP1 antibodies when a subunit MSP1 vaccine is introduced into populations living in areas where malaria is endemic. This together with previous observations that conserved determinants are important in MSP1-mediated immunity provides an optimistic outlook that a subunit MSP1 vaccine may be effective and practical for field applications in malaria-exposed populations.

Alleles↗