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 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 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 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.

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 A comparative analysis of memory B cell and antibody responses against Plasmodium falciparum merozoite surface protein 1 in children and adults from Uganda

2021 ◽  
Author(s):  
S Jake Gonzales ◽  
Kathleen N Clarke ◽  
Gayani Batugedara ◽  
Ashley E Braddom ◽  
Rolando Garza ◽  
...  
Keyword(s):  
Immune Response ◽  
Plasmodium Falciparum ◽  
B Cells ◽  
Surface Protein ◽  
Merozoite Surface Protein ◽  
Antibody Responses ◽  
Amino Acid Substitutions ◽  
Humoral Immune ◽  
Merozoite Surface Protein 1 ◽  
Specific Igg

Memory B cells (MBCs) and plasma antibodies against Plasmodium falciparum merozoite antigens are important components of the protective immune response against malaria. To gain understanding of how responses against P. falciparum develop in these two arms of the humoral immune system, we evaluated MBC and antibody responses against the most abundant merozoite antigen, merozoite surface protein 1 (MSP1), in individuals from a region in Uganda with high P. falciparum transmission. Our results showed that MSP1-specific B cells in adults with immunological protection against malaria were predominantly IgG+ classical MBCs, while children with incomplete protection mainly harbored IgM+ MSP1-specific classical MBCs. In contrast, anti-MSP1 plasma IgM reactivity was minimal in both children and adults. Instead, both groups showed high plasma IgG reactivity against MSP1 and whole merozoites, with broadening of the response against non-3D7 strains in adults. The antibodies encoded by MSP1-specific IgG+ MBCs carried high levels of amino acid substitutions and recognized relatively conserved epitopes on the highly variable MSP1 protein. Proteomics analysis of MSP119-specific IgG in plasma of an adult revealed a limited repertoire of anti-MSP1 antibodies, most of which were IgG1 or IgG3. Similar to MSP1-specific MBCs, anti-MSP1 IgGs had relatively high levels of amino acid substitutions and their sequences were predominantly found in classical MBCs, not atypical MBCs. Collectively, these results showed evolution of the MSP1-specific humoral immune response with cumulative P. falciparum exposure, with a shift from IgM+ to IgG+ B cell memory, diversification of B cells from germline, and stronger recognition of MSP1 variants by the plasma IgG repertoire.

scholarly journals Merozoite Surface Protein 1-Specific Immune Response Is Protective against Exoerythrocytic Forms of Plasmodium yoelii

2002 ◽  
Vol 70 (11) ◽  
pp. 6075-6082 ◽  
Author(s):  
Yuko Kawabata ◽  
Heiichiro Udono ◽  
Kiri Honma ◽  
Masakatsu Ueda ◽  
Hiroshi Mukae ◽  
...  
Keyword(s):  
Immune Response ◽  
Fusion Protein ◽  
Protective Immunity ◽  
Surface Protein ◽  
Merozoite Surface Protein ◽  
Plasmodium Yoelii ◽  
Parasite Development ◽  
Liver Stage ◽  
Merozoite Surface Protein 1 ◽  
Wide Range

ABSTRACT One of the difficulties in developing an effective malaria vaccine is the antigenic change of the parasite during the life cycle. It is desirable that vaccine-induced protective immunity be effective at different stages of parasite development. Merozoite surface protein 1 (MSP1) is a candidate vaccine antigen against blood-stage malaria, but it is also expressed in the exoerythrocytic forms. It was not known, however, whether the anti-MSP1 immune response is effective against the liver-stage malaria parasite. We generated a recombinant protein of MSP1 fused to heat-shock cognate protein 70 (hsc70) and studied its vaccination effect. When C57BL/6 mice were immunized with the fusion protein prior to challenge infection with Plasmodium yoelii sporozoites, the onset of parasitemia was delayed or no parasitemia was observed. To determine whether this was due to the protective immunity against liver-stage parasites, P. yoelii-specific rRNA in the infected liver was quantitated by real-time reverse transcription-PCR analysis. The level of parasite-specific rRNA was reduced in mice immunized with the fusion protein of MSP1 and hsc70 but not with hsc70 alone, indicating that MSP1-specific immunity can be protective against the exoerythrocytic form of the parasite. Furthermore, the adoptive transfer experiments of immune lymphocytes and serum into naive mice suggested that the protective immunity was dependent on cellular and not humoral immunity. Finally, the vaccine-induced protection was also observed in A/J, C3H, and BALB/c mice, suggesting that MSP1-specific protective immunity at the exoerythrocytic stage can be induced in animals over a wide range of genetic backgrounds.

scholarly journals Immunoglobulin G3 Antibodies Specific for the 19-Kilodalton Carboxyl-Terminal Fragment of Plasmodium yoelii Merozoite Surface Protein 1 Transfer Protection to Mice Deficient in Fc-γRI Receptors

2000 ◽  
Vol 68 (5) ◽  
pp. 3019-3022 ◽  
Author(s):  
Peter Vukovic ◽  
P. Mark Hogarth ◽  
Nadine Barnes ◽  
David C. Kaslow ◽  
Michael F. Good
Keyword(s):  
Malaria Vaccine ◽  
Vaccine Candidate ◽  
Surface Protein ◽  
Merozoite Surface Protein ◽  
Plasmodium Yoelii ◽  
Merozoite Surface Protein 1 ◽  
Specific Immunoglobulin ◽  
Malaria Vaccine Candidate ◽  
Main Action ◽  
Carboxyl Terminal

ABSTRACT Merozoite surface protein 1 (MSP-119) is a leading malaria vaccine candidate. Specific antibodies contribute to immunity; binding to macrophages is believed to represent the main action of malaria antibodies. We show that an MSP-119-specific immunoglobulin G3 (IgG3) monoclonal antibody can passively transfer protection to mice deficient in the α chain of Fc-γRI whose macrophages cannot bind IgG3.

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