scholarly journals Plasmodium falciparum 19-Kilodalton Merozoite Surface Protein 1 (MSP1)-Specific Antibodies That Interfere with Parasite GrowthIn VitroCan Inhibit MSP1 Processing, Merozoite Invasion, and Intracellular Parasite Development

2011 ◽  
Vol 80 (3) ◽  
pp. 1280-1287 ◽  
Author(s):  
David K. Moss ◽  
Edmond J. Remarque ◽  
Bart W. Faber ◽  
David R. Cavanagh ◽  
David E. Arnot ◽  
...  
Keyword(s):  
Vaccine Development ◽  
Surface Protein ◽  
Merozoite Surface Protein ◽  
Significant Inhibition ◽  
Parasite Growth ◽  
Proteolytic Processing ◽  
Parasite Development ◽  
Intracellular Parasite ◽  
Specific Antibodies ◽  
Merozoite Surface Protein 1

Merozoite surface protein 1 (MSP1) is a target for malaria vaccine development. Antibodies to the 19-kDa carboxy-terminal region referred to as MSP119inhibit erythrocyte invasion and parasite growth, with some MSP1-specific antibodies shown to inhibit the proteolytic processing of MSP1 that occurs at invasion. We investigated a series of antibodies purified from rabbits immunized with MSP119and AMA1 recombinant proteins for their ability to inhibit parasite growth, initially looking at MSP1 processing. Although significant inhibition of processing was mediated by several of the antibody samples, there was no clear relationship with overall growth inhibition by the same antibodies. However, no antibody samples inhibited processing but not invasion, suggesting that inhibition of MSP1 processing contributes to but is not the only mechanism of antibody-mediated inhibition of invasion and growth. Examining other mechanisms by which MSP1-specific antibodies inhibit parasite growth, we show that MSP119-specific antibodies are taken up into invaded erythrocytes, where they persist for significant periods and result in delayed intracellular parasite development. This delay may result from antibody interference with coalescence of MSP119-containing vesicles with the food vacuole. Antibodies raised against a modified recombinant MSP119sequence were more efficient at delaying intracellular growth than those to the wild-type protein. We propose that antibodies specific for MSP119can mediate inhibition of parasite growth by at least three mechanisms: inhibition of MSP1 processing, direct inhibition of invasion, and inhibition of parasite development following invasion. The balance between mechanisms may be modulated by modifying the immunogen used to induce the antibodies.

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 Antigenic Polymorphism and Naturally Acquired Antibodies to Plasmodium vivax Merozoite Surface Protein 1 in Rural Amazonians

2007 ◽  
Vol 14 (10) ◽  
pp. 1249-1259 ◽  
Author(s):  
Melissa S. Bastos ◽  
Mônica da Silva-Nunes ◽  
Rosely S. Malafronte ◽  
Erika Hellena E. Hoffmann ◽  
Gerhard Wunderlich ◽  
...  
Keyword(s):  
Plasmodium Vivax ◽  
Vaccine Development ◽  
Sequence Divergence ◽  
Surface Protein ◽  
Merozoite Surface Protein ◽  
Igg Antibodies ◽  
Antibody Recognition ◽  
Merozoite Surface Protein 1 ◽  
Relative Contribution ◽  
Repeated Infections

ABSTRACT Merozoite surface protein 1 of Plasmodium vivax (PvMSP-1), a major target for malaria vaccine development, contains six highly polymorphic domains interspersed with conserved sequences. Although there is evidence that the sequence divergence in PvMSP-1 has been maintained over 5 million years by balanced selection exerted by the host's acquired immunity, the variant specificity of naturally acquired antibodies to PvMSP-1 remains poorly investigated. Here, we show that 15 recombinant proteins corresponding to PvMSP-1 variants commonly found in local parasites were poorly recognized by 376 noninfected subjects aged 5 to 90 years exposed to malaria in rural Amazonia; less than one-third of them had detectable immunoglobulin G (IgG) antibodies to at least one variant of blocks 2, 6, and 10 that were expressed, although 54.3% recognized the invariant 19-kDa C-terminal domain PvMSP-119. Although the proportion of responders to PvMSP-1 variants increased substantially during subsequent acute P. vivax infections, the specificity of IgG antibodies did not necessarily match the PvMSP-1 variant(s) found in infecting parasites. We discuss the relative contribution of antigenic polymorphism, poor immunogenicity, and original antigenic sin (the skew in the specificity of antibodies elicited by exposure to new antigenic variants due to preexisting variant-specific responses) to the observed patterns of antibody recognition of PvMSP-1. We suggest that antibody responses to the repertoire of variable domains of PvMSP-1 to which subjects are continuously exposed are elicited only after several repeated infections and may require frequent boosting, with clear implications for the development of PvMSP-1-based subunit vaccines.

scholarly journals Allele-specific antibodies to Plasmodium vivax merozoite surface protein-1: prevalence and inverse relationship to haemoglobin levels during infection

2016 ◽  
Vol 15 (1) ◽  
Author(s):  
Nuno Sepúlveda ◽  
Cristiane Guimarães Morais ◽  
Luiza Carvalho Mourão ◽  
Matheus França Freire ◽  
Cor Jesus F. Fontes ◽  
...  
Keyword(s):  
Plasmodium Vivax ◽  
Inverse Relationship ◽  
Surface Protein ◽  
Merozoite Surface Protein ◽  
Specific Antibodies ◽  
Merozoite Surface Protein 1 ◽  
Allele Specific

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.

Sign in / Sign up

Export Citation Format

Share Document