scholarly journals Protective Immune Responses to the 42-Kilodalton (kDa) Region of Plasmodium yoelii Merozoite Surface Protein 1 Are Induced by the C-Terminal 19-kDa Region but Not by the Adjacent 33-kDa Region

2002 ◽  
Vol 70 (2) ◽  
pp. 820-825 ◽  
Author(s):  
Niklas Ahlborg ◽  
Irene T. Ling ◽  
Wendy Howard ◽  
Anthony A. Holder ◽  
Eleanor M. Riley
Keyword(s):  
Gene Segment ◽  
Surface Protein ◽  
Merozoite Surface Protein ◽  
Plasmodium Yoelii ◽  
Antibody Responses ◽  
Enzyme Linked Immunosorbent Assay ◽  
Igg Antibody ◽  
Merozoite Surface Protein 1 ◽  
Antibody Titers ◽  
Processing Product

ABSTRACT Vaccination of mice with the 42-kDa region of Plasmodium yoelii merozoite surface protein 1 (MSP142) or its 19-kDa C-terminal processing product (MSP119) can elicit protective antibody responses in mice. To investigate if the 33-kDa N-terminal fragment (MSP133) of MSP142 also induces protection, the gene segment encoding MSP133 was expressed as a glutathione S-transferase (GST) fusion protein. C57BL/6 and BALB/c mice were immunized with GST-MSP133 and subsequently challenged with the lethal P. yoelii YM blood stage parasite. GST-MSP133 failed to induce protection, and all mice developed patent parasitemia at a level similar to that in naive or control (GST-immunized) mice; mice immunized with GST-MSP119 were protected, as has been shown previously. Specific prechallenge immunoglobulin G (IgG) antibody responses to MSP1 were analyzed by enzyme-linked immunosorbent assay and immunofluorescence. Despite being unprotected, several mice immunized with MSP133 had antibody titers (of all IgG subclasses) that were comparable to or higher than those in mice that were protected following immunization with MSP119. The finding that P. yoelii MSP133 elicits strong but nonprotective antibody responses may have implications for the design of vaccines for humans based on Plasmodium falciparum or Plasmodium vivax MSP142.

scholarly journals Oral Immunization with a Combination of Plasmodium yoelii Merozoite Surface Proteins 1 and 4/5 Enhances Protection against Lethal Malaria Challenge

2004 ◽  
Vol 72 (10) ◽  
pp. 6172-6175 ◽  
Author(s):  
Lina Wang ◽  
Matthew W. Goschnick ◽  
Ross L. Coppel
Keyword(s):  
Escherichia Coli ◽  
Malaria Infection ◽  
Surface Protein ◽  
Merozoite Surface Protein ◽  
Oral Immunization ◽  
Plasmodium Yoelii ◽  
Antibody Responses ◽  
Surface Proteins ◽  
Merozoite Surface Protein 1

ABSTRACT Oral immunization of mice with Escherichia coli-expressed Plasmodium yoelii merozoite surface protein 4/5 or the C-terminal 19-kDa fragment of merozoite surface protein 1 induced systemic antibody responses and protected mice against lethal malaria infection. A combination of these two proteins administered orally conferred improved protection compared to that conferred by either protein administered alone.

scholarly journals Prediction of Merozoite Surface Protein 1 and Apical Membrane Antigen 1 Vaccine Efficacies against Plasmodium chabaudi Malaria Based on Prechallenge Antibody Responses

2008 ◽  
Vol 16 (3) ◽  
pp. 293-302 ◽  
Author(s):  
Michelle M. Lynch ◽  
Amy Cernetich-Ott ◽  
William P. Weidanz ◽  
James M. Burns
Keyword(s):  
Apical Membrane ◽  
Protective Efficacy ◽  
Surface Protein ◽  
Merozoite Surface Protein ◽  
Antibody Responses ◽  
Enzyme Linked Immunosorbent Assay ◽  
Plasmodium Chabaudi ◽  
Apical Membrane Antigen 1 ◽  
Merozoite Surface Protein 1 ◽  
Apical Membrane Antigen

ABSTRACT For the development of blood-stage malaria vaccines, there is a clear need to establish in vitro measures of the antibody-mediated and the cell-mediated immune responses that correlate with protection. In this study, we focused on establishing correlates of antibody-mediated immunity induced by immunization with apical membrane antigen 1 (AMA1) and merozoite surface protein 142 (MSP142) subunit vaccines. To do so, we exploited the Plasmodium chabaudi rodent model, with which we can immunize animals with both protective and nonprotective vaccine formulations and allow the parasitemia in the challenged animals to peak. Vaccine formulations were varied with regard to the antigen dose, the antigen conformation, and the adjuvant used. Prechallenge antibody responses were evaluated by enzyme-linked immunosorbent assay and were tested for a correlation with protection against nonlethal P. chabaudi malaria, as measured by a reduction in the peak level of parasitemia. The analysis showed that neither the isotype profile nor the avidity of vaccine-induced antibodies correlated with protective efficacy. However, high titers of antibodies directed against conformation-independent epitopes were associated with poor vaccine performance and may limit the effectiveness of protective antibodies that recognize conformation-dependent epitopes. We were able to predict the efficacies of the P. chabaudi AMA1 (PcAMA1) and P. chabaudi MSP142 (PcMSP142) vaccines only when the prechallenge antibody titers to both refolded and reduced/alkylated antigens were considered in combination. The relative importance of these two measures of vaccine-induced responses as predictors of protection differed somewhat for the PcAMA1 and the PcMSP142 vaccines, a finding confirmed in our final immunization and challenge study. A similar approach to the evaluation of vaccine-induced antibody responses may be useful during clinical trials of Plasmodium falciparum AMA1 and MSP142 vaccines.

scholarly journals The Oligomerization Domain of C4-Binding Protein (C4bp) Acts as an Adjuvant, and the Fusion Protein Comprised of the 19-Kilodalton Merozoite Surface Protein 1 Fused with the Murine C4bp Domain Protects Mice against Malaria

2008 ◽  
Vol 76 (8) ◽  
pp. 3817-3823 ◽  
Author(s):  
Solabomi A. Ogun ◽  
Laurence Dumon-Seignovert ◽  
Jean-Baptiste Marchand ◽  
Anthony A. Holder ◽  
Fergal Hill
Keyword(s):  
Fusion Protein ◽  
Binding Protein ◽  
Surface Protein ◽  
Merozoite Surface Protein ◽  
Plasmodium Yoelii ◽  
Protein Antigens ◽  
Merozoite Surface Protein 1 ◽  
Antibody Titers ◽  
Parasite Challenge ◽  
Oligomerization Domain

ABSTRACT Highly purified protein antigens are usually poor immunogens; in practice, adjuvants are needed to obtain satisfactory immune responses. Plasmodium yoelii 19-kDa merozoite surface protein 1 (MSP119) is a weak antigen, but mice vaccinated with this antigen in strong adjuvants can survive an otherwise lethal parasite challenge. Fusion proteins comprising this antigen fused to the oligomerization domain of the murine complement inhibitor C4-binding protein (C4bp) and a series of homologues have been produced. These C4bp domains acted as adjuvants for the fused antigen; the MSP119-murine C4bp fusion protein induced protective immunity in BALB/c mice. Because this fusion protein also induced antibodies against circulating murine C4bp, distantly related C4bp oligomerization domains fused to the same antigen were tested. These homologous domains did not induce antibodies against murine C4bp and, surprisingly, induced higher antibody titers against the antigen than the murine C4bp domain induced. These results demonstrate a new adjuvantlike effect of C4bp oligomerization domains.

scholarly journals Long-Lasting Protective Immune Response to the 19-Kilodalton Carboxy-Terminal Fragment of Plasmodium yoelii Merozoite Surface Protein 1 in Mice

2007 ◽  
Vol 14 (4) ◽  
pp. 342-347 ◽  
Author(s):  
Pimmada Jeamwattanalert ◽  
Yuvadee Mahakunkijcharoen ◽  
Leera Kittigul ◽  
Pakpimol Mahannop ◽  
Sathit Pichyangkul ◽  
...  
Keyword(s):  
Immune Response ◽  
Antibody Level ◽  
Surface Protein ◽  
Merozoite Surface Protein ◽  
Plasmodium Yoelii ◽  
Antibody Responses ◽  
Igg2a Antibody ◽  
Igg1 Antibody ◽  
Merozoite Surface Protein 1 ◽  
Antibody Levels

ABSTRACT Merozoite surface protein 1 (MSP1) is the major protein on the surface of the plasmodial merozoite, and its carboxy terminus, the 19-kDa fragment (MSP119), is highly conserved and effective in induction of a protective immune response against malaria parasite infection in mice and monkeys. However, the duration of the immune response has not been elucidated. As such, we immunized BALB/c mice with a standard four-dose injection of recombinant Plasmodium yoelii MSP119 formulated with Montanide ISA51 and CpG oligodeoxynucleotide (ODN) and monitored the MSP119-specific antibody levels for up to 12 months. The antibody titers persisted constantly over the period of time without significant waning, in contrast to the antibody levels induced by immunization with Freund's adjuvant, where the antibody levels gradually declined to significantly lower levels 12 months after immunization. Investigation of immunoglobulin G (IgG) subclass longevity revealed that only the IgG1 antibody level (Th2 type-driven response) decreased significantly by 6 months, while the IgG2a antibody level (Th1 type-driven response) did not change over the 12 months after immunization, but the boosting effect was seen in the IgG1 antibody responses but not in the IgG2a antibody responses. After challenge infection, all immunized mice survived with negligibly patent parasitemia. These findings suggest that protective immune responses to MSP119 following immunization using oil-based Montanide ISA51 and CpG ODN as an adjuvant are very long-lasting and encourage clinical trials for malaria vaccine development.

scholarly journals Inhibitory Antibodies Specific for the 19-Kilodalton Fragment of Merozoite Surface Protein 1 Do Not Correlate with Delayed Appearance of Infection with Plasmodium falciparum in Semi-Immune Individuals in Vietnam

2009 ◽  
Vol 77 (10) ◽  
pp. 4510-4517 ◽  
Author(s):  
E. Elsa Herdiana Murhandarwati ◽  
Lina Wang ◽  
Casilda G. Black ◽  
Doan Hanh Nhan ◽  
Thomas L. Richie ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Surface Protein ◽  
Merozoite Surface Protein ◽  
Plasmodium Yoelii ◽  
Enzyme Linked Immunosorbent Assay ◽  
Acquired Immunity ◽  
Homologous Region ◽  
Significant Component ◽  
Merozoite Surface Protein 1 ◽  
Inhibitory Antibodies

ABSTRACT Inhibitory antibodies specific for the 19-kDa fragment of merozoite surface protein 1 (MSP119) are a significant component of inhibitory responses in individuals immune to malaria. Nevertheless, conflicting results have been obtained in determining whether this antibody specificity correlates with protection in residents of areas where malaria is endemic. In this study, we examined sera collected from a population of semi-immune individuals living in an area of Vietnam with meso-endemicity during a 6-month period. We used two Plasmodium falciparum parasite lines that express either endogenous MSP119 or the homologous region from Plasmodium yoelii to measure the MSP119-specific inhibitory activity. We showed that (i) the level of MSP119-specific inhibitory antibodies was not associated with a delay in P. falciparum infection, (ii) MSP119-specific inhibitory antibodies declined significantly during the convalescent period after infection, and (iii) there was no significant correlation between the MSP119-specific inhibitory antibodies and the total antibodies measured by enzyme-linked immunosorbent assay. These results have implications for understanding naturally acquired immunity to malaria and for the development and evaluation of MSP119-based vaccines.

scholarly journals Protection of Mice against Plasmodium yoelii Sporozoite Challenge with P. yoelii Merozoite Surface Protein 1 DNA Vaccines

1998 ◽  
Vol 66 (7) ◽  
pp. 3457-3461 ◽  
Author(s):  
Sylvia I. Becker ◽  
Ruobing Wang ◽  
Richard C. Hedstrom ◽  
Joao C. Aguiar ◽  
Trevor R. Jones ◽  
...  
Keyword(s):  
Recombinant Protein ◽  
Dna Vaccines ◽  
Surface Protein ◽  
Merozoite Surface Protein ◽  
Plasmodium Yoelii ◽  
Partial Protection ◽  
Merozoite Surface Protein 1 ◽  
C Terminus ◽  
Antibody Titers ◽  
C And N

ABSTRACT Immunization of mice with DNA vaccines encoding the full-length form and C and N termini of Plasmodium yoelii merozoite surface protein 1 provided partial protection against sporozoite challenge and resulted in boosting of antibody titers after challenge. In C57BL/6 mice, two DNA vaccines provided protection comparable to that of recombinant protein consisting of the C terminus in Freund’s adjuvant.

scholarly journals Levels of Antibody to Conserved Parts of Plasmodium falciparum Merozoite Surface Protein 1 in Ghanaian Children Are Not Associated with Protection from Clinical Malaria

1999 ◽  
Vol 67 (5) ◽  
pp. 2131-2137 ◽  
Author(s):  
Daniel Dodoo ◽  
Thor G. Theander ◽  
Jorgen A. L. Kurtzhals ◽  
Kojo Koram ◽  
Eleanor Riley ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Surface Protein ◽  
Merozoite Surface Protein ◽  
Clinical Malaria ◽  
Antibody Responses ◽  
Enzyme Linked Immunosorbent Assay ◽  
Human Antibody ◽  
Merozoite Surface Protein 1 ◽  
Egf Domain ◽  
Antibody Specificities

ABSTRACT The 19-kDa conserved C-terminal part of the Plasmodium falciparum merozoite surface protein 1 (PfMSP119) is a malaria vaccine candidate antigen, and human antibody responses to PfMSP119 have been associated with protection against clinical malaria. In this longitudinal study carried out in an area of stable but seasonal malaria transmission with an estimated parasite inoculation of about 20 infective bites/year, we monitored 266 3- to 15-year-old Ghanaian children clinically and parasitologically over a period of 18 months. Blood samples were collected at the beginning of the study before the major malaria season in April and after the season in November. Using enzyme-linked immunosorbent assay, we measured antibody responses to recombinant gluthathioneS-transferase–PfMSP119 fusion proteins corresponding to the Wellcome and MAD20 allelic variants in these samples. Prevalence of antibodies recognizing the Wellcome 19 construct containing both epidermal growth factor (EGF)-like motifs in Wellcome type PfMSP119 was about 30%. Prevalence of antibodies to constructs containing only the first EGF domain from either Wellcome or MAD20 type PfMSP119 was about 15%, whereas antibodies recognizing a construct containing only the second EGF domain of MAD20 type PfMSP119 was found in only about 4% of the donors. Neither the prevalence nor the levels of any of the antibody specificities varied significantly with season, age, or sex. Significantly, and in contrast to previous reports from other parts of West Africa, we found no evidence of an association between antibody responses to PfMSP119and clinical protection against malaria.

scholarly journals Genetic diversity and immunogenicity of the merozoite surface protein 1 C-terminal 19-kDa fragment of Plasmodium ovale imported from Africa into China

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Qinwen Xu ◽  
Sihong Liu ◽  
Kokouvi Kassegne ◽  
Bo Yang ◽  
Jiachen Lu ◽  
...  
Keyword(s):  
Genetic Diversity ◽  
Immune Responses ◽  
Expression System ◽  
Surface Protein ◽  
Merozoite Surface Protein ◽  
Enzyme Linked Immunosorbent Assay ◽  
High Avidity ◽  
Plasmodium Ovale ◽  
Merozoite Surface Protein 1 ◽  
Proliferation Assays

Abstract Background Merozoite surface protein 1 (MSP1) plays an essential role in erythrocyte invasion by malaria parasites. The C-terminal 19-kDa region of MSP1 has long been considered one of the major candidate antigens for a malaria blood-stage vaccine against Plasmodium falciparum. However, there is limited information on the C-terminal 19-kDa region of Plasmodium ovale MSP1 (PoMSP119). This study aims to analyze the genetic diversity and immunogenicity of PoMSP119. Methods A total of 37 clinical Plasmodium ovale isolates including Plasmodium ovale curtisi and Plasmodium ovale wallikeri imported from Africa into China and collected during the period 2012–2016 were used. Genomic DNA was used to amplify P. ovale curtisi (poc) msp119 (pocmsp119) and P. ovale wallikeri (pow) msp119 (powmsp119) genes by polymerase chain reaction. The genetic diversity of pomsp119 was analyzed using the GeneDoc version 6 programs. Recombinant PoMSP119 (rPoMSP119)-glutathione S-transferase (GST) proteins were expressed in an Escherichia coli expression system and analyzed by western blot. Immune responses in BALB/c mice immunized with rPoMSP119-GST were determined using enzyme-linked immunosorbent assay. In addition, antigen-specific T cell responses were assessed by lymphocyte proliferation assays. A total of 49 serum samples from healthy individuals and individuals infected with P. ovale were used for the evaluation of natural immune responses by using protein microarrays. Results Sequences of pomsp119 were found to be thoroughly conserved in all the clinical isolates. rPoMSP119 proteins were efficiently expressed and purified as ~ 37-kDa proteins. High antibody responses in mice immunized with rPoMSP119-GST were observed. rPoMSP119-GST induced high avidity indexes, with an average of 92.57% and 85.32% for rPocMSP119 and rPowMSP119, respectively. Cross-reactivity between rPocMSP119 and rPowMSP119 was observed. Cellular immune responses to rPocMSP119 (69.51%) and rPowMSP119 (52.17%) induced in rPocMSP119- and rPowMSP119-immunized mice were found in the splenocyte proliferation assays. The sensitivity and specificity of rPoMSP119-GST proteins for the detection of natural immune responses in patients infected with P. ovale were 89.96% and 75%, respectively. Conclusions This study revealed highly conserved gene sequences of pomsp119. In addition, naturally acquired humoral immune responses against rPoMSP1 were observed in P. ovale infections, and high immunogenicity of rPoMSP119 in mice was also identified. These instructive findings should encourage further testing of PoMSP119 for rational vaccine design. Graphical abstract

scholarly journals Nature and Specificity of the Required Protective Immune Response That Develops Postchallenge in Mice Vaccinated with the 19-Kilodalton Fragment of Plasmodium yoelii Merozoite Surface Protein 1

2002 ◽  
Vol 70 (11) ◽  
pp. 6013-6020 ◽  
Author(s):  
Jiraprapa Wipasa ◽  
Huji Xu ◽  
Morris Makobongo ◽  
Michelle Gatton ◽  
Anthony Stowers ◽  
...  
Keyword(s):  
Immune Response ◽  
Antibody Response ◽  
Specific Antibody ◽  
Natural Infection ◽  
Surface Protein ◽  
Merozoite Surface Protein ◽  
Plasmodium Yoelii ◽  
Specific Antibody Response ◽  
Specific Antibodies ◽  
Merozoite Surface Protein 1

ABSTRACT Immunity induced by the 19-kDa fragment of Plasmodium yoelii merozoite surface protein 1 (MSP119) is dependent on high titers of specific antibodies present at the time of challenge and a continuing active immune response postinfection. However, the specificity of the active immune response postinfection has not been defined. In particular, it is not known whether anti-MSP119 antibodies that arise following infection alone are sufficient for protection. We developed systems to investigate whether an MSP119-specific antibody response alone both prechallenge and postchallenge is sufficient for protection. We were able to exclude antibodies with other specificities, as well as any contribution of MSP119-specific CD4+ T cells acting independent of antibody, and we concluded that an immune response focused solely on MSP119-specific antibodies is sufficient for protection. The data imply that the ability of natural infection to boost an MSP119-specific antibody response should greatly improve vaccine efficacy.

scholarly journals Human Leukocyte Antigen Class II Alleles Influence Levels of Antibodies to the Plasmodium falciparum Asexual-Stage Apical Membrane Antigen 1 but Not to Merozoite Surface Antigen 2 and Merozoite Surface Protein 1

2004 ◽  
Vol 72 (5) ◽  
pp. 2762-2771 ◽  
Author(s):  
Armead H. Johnson ◽  
Rose G. F. Leke ◽  
Nancy R. Mendell ◽  
Dewon Shon ◽  
Young Ju Suh ◽  
...  
Keyword(s):  
Apical Membrane ◽  
Surface Protein ◽  
Human Leukocyte ◽  
Merozoite Surface Protein ◽  
Antibody Responses ◽  
Apical Membrane Antigen 1 ◽  
Leukocyte Antigen ◽  
Merozoite Surface Protein 1 ◽  
Merozoite Surface Antigen ◽  
Antibody Levels

ABSTRACT The apical membrane antigen 1 (AMA1), merozoite surface antigen 2 (MSA2), and merozoite surface protein 1 (MSP1) are asexual-stage proteins currently being evaluated for inclusion in a vaccine for Plasmodium falciparum. Accordingly, it is important to understand factors that control antibody responses to these antigens. Antibody levels in plasma from residents of Etoa, Cameroon, between the ages of 5 and 70 years, were determined using recombinant AMA1, MSA2, and the N-terminal region of MSP1 (MSP1-190L). In addition, antibody responses to four variants of the C-terminal region of MSP1 (MSP119) were assessed. Results showed that all individuals produced antibodies to AMA1, MSA2, and MSP1-190L; however, a proportion of individuals never produced antibodies to the MSP119 variants, although the percentage of nonresponders decreased with age. The influence of age and human leukocyte antigen (HLA)-DRB1/DQB1 alleles on antibody levels was evaluated using two-way analysis of variance. Age was correlated with levels of antibodies to AMA1 and MSP119 but not with levels of antibodies to MSA2 and MSP1-190L. No association was found between a single HLA allele and levels of antibodies to MSA2, MSP1-190L, or any of the MSP119 variants. However, individuals positive for DRB1*1201 had higher levels of antibodies to the variant of recombinant AMA1 tested than did individuals of all other HLA types. Since the effect was seen across all age groups, HLA influenced the level but not the rate of antibody acquisition. This association for AMA1, combined with the previously reported association between HLA class II alleles and levels of antibodies to rhoptry-associated protein 1 (RAP1) and RAP2, indicates that HLA influences the levels of antibodies to three of the five vaccine candidate antigens that we have evaluated.

Sign in / Sign up

Export Citation Format

Share Document