scholarly journals Linkage of Exogenous T-cell Epitopes to the 19-Kilodalton Region of Plasmodium yoelii Merozoite Surface Protein 1 (MSP119) Can Enhance Protective Immunity against Malaria and Modulate the Immunoglobulin Subclass Response to MSP119

2000 ◽  
Vol 68 (4) ◽  
pp. 2102-2109 ◽  
Author(s):  
Niklas Ahlborg ◽  
Irene T. Ling ◽  
Anthony A. Holder ◽  
Eleanor M. Riley
Keyword(s):  
T Cell ◽  
Protective Immunity ◽  
Cell Epitope ◽  
Surface Protein ◽  
Merozoite Surface Protein ◽  
Plasmodium Yoelii ◽  
Mouse Strains ◽  
Igg Subclass ◽  
T Cell Epitope ◽  
Merozoite Surface Protein 1

ABSTRACT The degree of protection against Plasmodium yoeliiasexual blood stages induced by immunization of mice with the 19-kDa region of merozoite surface protein 1 (MSP119) is H-2 dependent. As a strategy to improve the protection, mouse strains with disparate H-2 haplotypes were immunized with glutathioneS-transferase (GST)–MSP119 proteins including either a universal T-cell epitope from tetanus toxin (P2) or an I-Ak-restricted T-cell epitope (P8) fromPlasmodium falciparum Pf332. In H-2k mice which are poorly protected following immunization with GST-MSP119, GST-P2-MSP119 significantly improved the protection. In mice partially (H-2k/b) or well protected by GST-MSP119 (H-2d and H-2b), P2 did not further increase the protection. However, the protection of H-2k/b mice and to some extent H-2k mice was improved by immunization with GST-P8-MSP119. The magnitudes of immunoglobulin G1 (IgG1) and IgG2a responses in mice immunized with the GST-MSP119variants correlated with low peak parasitemia, indicating a protective capacity of these IgG subclasses. In H-2k mice immunized with GST-P2-MSP119, both IgG1 and IgG2a responses were significantly enhanced. The epitope P2 appeared to have a general ability to modulate the IgG subclass response since all four mouse strains displayed elevated IgG2a and/or IgG2b levels after immunization with GST-P2-MSP119. In contrast, GST-P8-MSP119induced a slight enhancement of IgG responses in H-2k/b and H-2k mice without any major shift in IgG subclass patterns. The ability to improve the protective immunity elicited by P. yoelii MSP119 may have implications for improvement of human vaccines based on P. falciparumMSP119.

scholarly journals Induction of Protective Immunity against Malaria by Priming-Boosting Immunization with Recombinant Cold-Adapted Influenza and Modified Vaccinia Ankara Viruses Expressing a CD8+-T-Cell Epitope Derived from the Circumsporozoite Protein of Plasmodium yoelii

2003 ◽  
Vol 77 (21) ◽  
pp. 11859-11866 ◽  
Author(s):  
Gloria González-Aseguinolaza ◽  
Yurie Nakaya ◽  
Alberto Molano ◽  
Edward Dy ◽  
Mariano Esteban ◽  
...  
Keyword(s):  
Influenza Virus ◽  
T Cell ◽  
Vaccinia Virus ◽  
Protective Immunity ◽  
Cell Epitope ◽  
Plasmodium Yoelii ◽  
T Cell Epitope ◽  
Cold Adapted ◽  
Modified Vaccinia Virus Ankara ◽  
First Time

ABSTRACT We immunized mice with an attenuated (cold-adapted) influenza virus followed by an attenuated vaccinia virus (modified vaccinia virus Ankara), both expressing a CD8+-T-cell epitope derived from malaria sporozoites. This vaccination regimen elicited high levels of protection against malaria. This is the first time that the vaccine efficacy of a recombinant cold-adapted influenza virus vector expressing a foreign antigen has been evaluated.

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 Analysis of Immunological Nonresponsiveness to the 19-Kilodalton Fragment of Merozoite Surface Protein 1 of Plasmodium yoelii: Rescue by Chemical Conjugation to Diphtheria Toxoid (DT) and Enhancement of Immunogenicity by Prior DT Vaccination

2003 ◽  
Vol 71 (10) ◽  
pp. 5700-5713 ◽  
Author(s):  
Danielle I. Stanisic ◽  
Laura B. Martin ◽  
Xue Q. Liu ◽  
David Jackson ◽  
Juan Cooper ◽  
...  
Keyword(s):  
Synthetic Peptides ◽  
Surface Protein ◽  
Merozoite Surface Protein ◽  
Plasmodium Yoelii ◽  
Diphtheria Toxoid ◽  
Mouse Strains ◽  
Major Histocompatibility Complex Haplotype ◽  
Specific Antibodies ◽  
Merozoite Surface Protein 1 ◽  
Chemical Conjugation

ABSTRACT The Plasmodium merozoite surface protein 1 (MSP1) is a leading vaccine candidate for protecting against the blood stage of malaria. Previous studies have shown that the 19-kDa carboxyl terminus of this protein is able to induce protective immunity in some monkey and mouse strains. We show that immunization with the recombinant Plasmodium yoelii 19-kDa fragment of MSP1 (MSP119) expressed in Saccharomyces cerevisiae (yMSP119) can induce protective antibodies in several inbred mouse strains and one outbred mouse strain. However, mice expressing the H-2s major histocompatibility complex haplotype are unable to generate yMSP119-specific antibodies. While synthetic peptides derived from MSP119 are immunogenic in B10.S mice, they cannot function as helper epitopes, and immunization with yMSP119 does not induce T cells that recognize the recombinant protein or synthetic peptides corresponding to its sequence. Nonresponsiveness could be overcome by using chemical linkers to conjugate yMSP119 to diphtheria toxoid (DT), resulting in immunogens capable of inducing protective yMSP119-specific antibodies in both MSP119-responsive and otherwise nonresponsive mouse strains. The ability of sera from mice immunized with the conjugate to inhibit binding of a protective monoclonal antibody (MAb 302) to yMSP119 correlated strongly with a delay in the prepatent period. Chemical conjugation of yMSP119 to DT may be a preferred method to enhance immunogenicity, as carrier priming experiments demonstrated that an existing immune response to DT enhanced a subsequent antibody response to yMSP119 after vaccination with yMSP119-DT. These results have important implications for the development of a malaria vaccine to protect a population with diverse HLAs.

scholarly journals The structure of Plasmodium yoelii merozoite surface protein 1 19 , antibody specificity and implications for malaria vaccine design

Open Biology ◽  
2014 ◽  
Vol 4 (1) ◽  
pp. 130091 ◽  
Author(s):  
Rachel D. Curd ◽  
Berry Birdsall ◽  
Madhusudan Kadekoppala ◽  
Solabomi A. Ogun ◽  
Geoffrey Kelly ◽  
...  
Keyword(s):  
Protective Immunity ◽  
Vaccine Development ◽  
Surface Protein ◽  
Merozoite Surface Protein ◽  
Plasmodium Yoelii ◽  
Target Antigen ◽  
Asexual Blood Stage ◽  
Merozoite Surface Protein 1 ◽  
Protective Antibodies ◽  
Blood Stage Malaria

Merozoite surface protein 1 (MSP1) has been identified as a target antigen for protective immune responses against asexual blood stage malaria, but effective vaccines based on MSP1 have not been developed so far. We have modified the sequence of Plasmodium yoelii MSP1 19 (the C-terminal region of the molecule) and examined the ability of the variant proteins to bind protective monoclonal antibodies and to induce protection by immunization. In parallel, we examined the structure of the protein and the consequences of the amino acid changes. Naturally occurring sequence polymorphisms reduced the binding of individual protective antibodies, indicating that they contribute to immune evasion, but immunization with these variant proteins still provided protective immunity. One variant that resulted in the localized distortion of a loop close to the N-terminus of MSP1 19 almost completely ablated protection by immunization, indicating the importance of this region of MSP1 19 as a target for protective immunity and in vaccine development.

scholarly journals Association between Protection against Clinical Malaria and Antibodies to Merozoite Surface Antigens in an Area of Hyperendemicity in Myanmar: Complementarity between Responses to Merozoite Surface Protein 3 and the 220-Kilodalton Glutamate-Rich Protein

2004 ◽  
Vol 72 (1) ◽  
pp. 247-252 ◽  
Author(s):  
Soe Soe ◽  
Michael Theisen ◽  
Christian Roussilhon ◽  
Khin-Saw- Aye ◽  
Pierre Druilhe
Keyword(s):  
Protective Immunity ◽  
Surface Protein ◽  
Merozoite Surface Protein ◽  
Clinical Malaria ◽  
Strong Response ◽  
Vaccine Candidates ◽  
Follow Up Study ◽  
Merozoite Surface Protein 1 ◽  
Complementary Effect

ABSTRACT We performed a longitudinal clinical and parasitological follow-up study in OoDo, a village in southeast Asia in which malaria is hyperendemic, in order to assess the association between protection against malaria attacks and antibodies to three currently evaluated vaccine candidates, merozoite surface protein 1 (MSP1), MSP3, and the 220-kDa glutamate-rich protein (GLURP) from Plasmodium falciparum. Our results showed that the levels of cytophilic immunoglobulin G3 (IgG3) antibodies against conserved regions of MSP3 and GLURP were significantly correlated with protection against clinical P. falciparum malaria. In contrast, the levels of noncytophilic IgG4 antibodies against GLURP increased with the number of malaria attacks. Furthermore, we observed a complementary effect of the MSP3- and GLURP-specific IgG3 antibodies in relation to malaria protection. In the individuals that did not respond to one of the antigens, a strong response to the other antigen was consistently detected and was associated with protection, suggesting that induction of antibodies against both MSP3 and GLURP could be important for the development of protective immunity. The complementarity of the responses to the two main targets of antibody-dependent cellular inhibition identified to date provides the first rational basis for combining these two antigens in a hybrid vaccine formulation.

The carboxy-terminus of merozoite surface protein 1: structure, specific antibodies and immunity to malaria

Parasitology ◽  
2009 ◽  
Vol 136 (12) ◽  
pp. 1445-1456 ◽  
Author(s):  
A. A. HOLDER
Keyword(s):  
Protective Immunity ◽  
First Generation ◽  
Surface Protein ◽  
Merozoite Surface Protein ◽  
Carboxy Terminus ◽  
Vaccine Candidates ◽  
Merozoite Surface Protein 1 ◽  
Early Results ◽  
Experimental Approaches

SUMMARYOver the last 30 years, evidence has been gathered suggesting that merozoite surface protein 1 (MSP1) is a target of protective immunity against malaria. In a variety of experimental approaches usingin vitromethodology, animal models and sero-epidemiological techniques, the importance of antibody against MSP1 has been established but we are still finding out what are the mechanisms involved. Now that clinical trials of MSP1 vaccines are underway and the early results have been disappointing, it is increasingly clear that we need to know more about the mechanisms of immunity, because a better understanding will highlight the limitations of our current assays and identify the improvements required. Understanding the structure of MSP1 will help us design and engineer better antigens that are more effective than the first generation of vaccine candidates. This review is focused on the carboxy-terminus of MSP1.

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.

Sign in / Sign up

Export Citation Format

Share Document