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 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.

scholarly journals N-TerminalPlasmodium vivaxMerozoite Surface Protein-1, a Potential Subunit for Malaria Vivax Vaccine

2013 ◽  
Vol 2013 ◽  
pp. 1-7 ◽  
Author(s):  
Fernanda G. Versiani ◽  
Maria E. Almeida ◽  
Luis A. Mariuba ◽  
Patricia P. Orlandi ◽  
Paulo A. Nogueira
Keyword(s):  
Immune Response ◽  
Protective Immunity ◽  
Malaria Vaccine ◽  
Natural Infection ◽  
Surface Protein ◽  
Merozoite Surface Protein ◽  
Humoral Immune ◽  
Merozoite Surface Protein 1 ◽  
The Western Pacific

The human malaria is widely distributed in the Middle East, Asia, the western Pacific, and Central and South America.Plasmodium vivaxstarted to have the attention of many researchers since it is causing diseases to millions of people and several reports of severe malaria cases have been noticed in the last few years. The lack ofin vitrocultures forP. vivaxrepresents a major delay in developing a functional malaria vaccine. One of the major candidates to antimalarial vaccine is the merozoite surface protein-1 (MSP1), which is expressed abundantly on the merozoite surface and capable of activating the host protective immunity. Studies have shown that MSP-1 possesses highly immunogenic fragments, capable of generating immune response and protection in natural infection in endemic regions. This paper shows humoral immune response to different proteins of PvMSP1 and the statement of N-terminal to be added to the list of potential candidates for malaria vivax vaccine.

scholarly journals Merozoite Surface Protein 1 of Plasmodium vivax Induces a Protective Response against Plasmodium cynomolgi Challenge in Rhesus Monkeys

2005 ◽  
Vol 73 (9) ◽  
pp. 5936-5944 ◽  
Author(s):  
Sheetij Dutta ◽  
Deep C. Kaushal ◽  
Lisa A. Ware ◽  
Sunil K. Puri ◽  
Nuzhat A. Kaushal ◽  
...  
Keyword(s):  
Plasmodium Vivax ◽  
Protective Efficacy ◽  
High Titer ◽  
Surface Protein ◽  
Merozoite Surface Protein ◽  
Control Group ◽  
Merozoite Surface Protein 1 ◽  
Significant Difference ◽  
Peak Parasitemia

ABSTRACT The 42-kDa fragment of the merozoite surface protein 1 (MSP-142) is a leading candidate for the development of a vaccine to control malaria. We previously reported a method for the production of Plasmodium vivax MSP-142 (PvMSP-142) as a soluble protein (S. Dutta, L. W. Ware, A. Barbosa, C. F. Ockenhouse, and D. E. Lanar, Infect. Immun. 69:5464-5470, 2001). We report here a process to manufacture the same PvMSP-142 protein but as an insoluble inclusion body-derived protein which was then refolded in vitro. We compared the immunogenicity and protective efficacy of the soluble and refolded forms of PvMSP-142 protein by using a heterologous but closely related P. cynomolgi-rhesus monkey challenge model. As comparative controls we also expressed, purified, and immunized rhesus with the soluble and refolded forms of the P. cynomolgi MSP-142 (PcMSP-142) proteins. All proteins induced equally high-titer, cross-reacting antibodies. Upon challenge with P. cynomolgi, none of the MSP-142-vaccinated groups demonstrated sterile protection or a delay in the prepatent period. However, following an initial rise in parasitemia, all MSP-1-vaccinated animals had significantly lower parasite burdens as indicated by lower cumulative parasitemia, lower peak parasitemia, lower secondary peak parasitemia, and lower average daily parasitemia compared to the adjuvant control group (P < 0.05). Except the soluble PcMSP-142 group, monkeys in all other groups had fewer numbers of days with parasitemia of >10,000 parasites mm−3. Interestingly, there was no significant difference in the level of partial protection observed in the homologous and heterologous groups in this challenge model. The soluble and refolded forms of PcMSP-142 and PvMSP-142 proteins also appeared to have a similar partially protective effect.

scholarly journals Plasmodium falciparum Merozoite Surface Protein 1 (MSP-1)-MSP-3 Chimeric Protein: Immunogenicity Determined with Human-Compatible Adjuvants and Induction of Protective Immune Response

2009 ◽  
Vol 78 (2) ◽  
pp. 872-883 ◽  
Author(s):  
Suman Mazumdar ◽  
Paushali Mukherjee ◽  
Syed Shams Yazdani ◽  
S. K. Jain ◽  
Asif Mohmmed ◽  
...  
Keyword(s):  
Immune Response ◽  
Plasmodium Falciparum ◽  
Fusion Protein ◽  
Malaria Vaccine ◽  
Chimeric Protein ◽  
Surface Protein ◽  
Merozoite Surface Protein ◽  
Protective Immune Response ◽  
Merozoite Surface Protein 1

ABSTRACT A chimeric gene, MSP-Fu24 , was constructed by genetically coupling immunodominant, conserved regions of the two leading malaria vaccine candidates, Plasmodium falciparum merozoite surface protein 1 (C-terminal 19-kDa region [PfMSP-119]) and merozoite surface protein 3 (11-kDa conserved region [PfMSP-311]). The recombinant MSP-Fu24 protein was produced in Escherichia coli cells and purified to homogeneity by a two-step purification process with a yield of ∼30 mg/liter. Analyses of conformational properties of MSP-Fu24 using PfMSP-119-specific monoclonal antibody showed that the conformational epitopes of PfMSP-119 that may be critical for the generation of the antiparasitic immune response remained intact in the fusion protein. Recombinant MSP-Fu24 was highly immunogenic in mice and in rabbits when formulated with two different human-compatible adjuvants and induced an immune response against both PfMSP-119 and PfMSP-311. Purified anti-MSP-Fu24 antibodies showed invasion inhibition of P. falciparum 3D7 and FCR parasites, and this effect was found to be dependent on antibodies specific for the PfMSP-119 component. The protective potential of MSP-Fu24 was demonstrated by in vitro parasite growth inhibition using an antibody-dependent cell inhibition (ADCI) assay with anti-MSP-Fu24 antibodies. Overall, the antiparasitic activity was mediated by a combination of growth-inhibitory antibodies generated by both the PfMSP-119 and PfMSP-311 components of the MSP-Fu24 protein. The antiparasitic activities elicited by anti-MSP-Fu24 antibodies were comparable to those elicited by antibodies generated with immunization with a physical mixture of two component antigens, PfMSP-119 and PfMSP-311. The fusion protein induces a protective immune response with human-compatible adjuvants and may form a part of a multicomponent malaria vaccine.

scholarly journals Analysis of Antibodies Directed against Merozoite Surface Protein 1 of the Human Malaria Parasite Plasmodium falciparum

2006 ◽  
Vol 74 (2) ◽  
pp. 1313-1322 ◽  
Author(s):  
Ute Woehlbier ◽  
Christian Epp ◽  
Christian W. Kauth ◽  
Rolf Lutz ◽  
Carole A. Long ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Surface Protein ◽  
Merozoite Surface Protein ◽  
Merozoite Surface Protein 1 ◽  
Erythrocyte Invasion ◽  
Parasite Plasmodium ◽  
Parasite Plasmodium Falciparum ◽  
Parasite Multiplication ◽  
Parasite Replication

ABSTRACT The 190-kDa merozoite surface protein 1 (MSP-1) of Plasmodium falciparum, an essential component in the parasite's life cycle, is a primary candidate for a malaria vaccine. Rabbit antibodies elicited by the heterologously produced MSP-1 processing products p83, p30, p38, and p42, derived from strain 3D7, were analyzed for the potential to inhibit in vitro erythrocyte invasion by the parasite and parasite growth. Our data show that (i) epitopes recognized by antibodies, which inhibit parasite replication, are distributed throughout the entire MSP-1 molecule; (ii) when combined, antibodies specific for different regions of MSP-1 inhibit in a strictly additive manner; (iii) anti-MSP-1 antibodies interfere with erythrocyte invasion as well as with the intraerythrocytic growth of the parasite; and (iv) antibodies raised against MSP-1 of strain 3D7 strongly cross-inhibit replication of the heterologous strain FCB-1. Accordingly, anti-MSP-1 antibodies appear to be capable of interfering with parasite multiplication at more than one level. Since the overall immunogenicity profile of MSP-1 in rabbits closely resembles that found in sera of Aotus monkeys immunized with parasite-derived MSP-1 and of humans semi-immune to malaria from whom highly inhibiting antigen-specific antibodies were recovered, we consider the findings reported here to be relevant for the development of MSP-1-based vaccines against malaria.

scholarly journals Anti-Apical-Membrane-Antigen-1 Antibody Is More Effective than Anti-42-Kilodalton-Merozoite-Surface-Protein-1 Antibody in Inhibiting Plasmodium falciparum Growth, as Determined by the In Vitro Growth Inhibition Assay

2009 ◽  
Vol 16 (7) ◽  
pp. 963-968 ◽  
Author(s):  
Kazutoyo Miura ◽  
Hong Zhou ◽  
Ababacar Diouf ◽  
Samuel E. Moretz ◽  
Michael P. Fay ◽  
...  
Keyword(s):  
Apical Membrane ◽  
Surface Protein ◽  
Merozoite Surface Protein ◽  
Inhibition Assay ◽  
Growth Inhibition Assay ◽  
Apical Membrane Antigen 1 ◽  
Merozoite Surface Protein 1 ◽  
Growth Inhibitory ◽  
Growth Inhibitory Activity

ABSTRACT Apical membrane antigen 1 (AMA1) and the 42-kDa merozoite surface protein 1 (MSP142) are leading malaria vaccine candidates. Several preclinical and clinical trials have been conducted, and an in vitro parasite growth inhibition assay has been used to evaluate the biological activities of the resulting antibodies. In a U.S. phase 1 trial with AMA1-C1/Alhydrogel plus CPG 7909, the vaccination elicited anti-AMA1 immunoglobulin G (IgG) which showed up to 96% inhibition. However, antibodies induced by MSP142-C1/Alhydrogel plus CPG 7909 vaccine showed less than 32% inhibition in vitro. To determine whether anti-MSP142 IgG had less growth-inhibitory activity than anti-AMA1 IgG in vitro, the amounts of IgG that produced 50% inhibition of parasite growth (Ab50) were compared for rabbit and human antibodies. The Ab50s of rabbit and human anti-MSP142 IgGs were significantly higher (0.21 and 0.62 mg/ml, respectively) than those of anti-AMA1 IgGs (0.07 and 0.10 mg/ml, respectively) against 3D7 parasites. Ab50 data against FVO parasites also demonstrated significant differences. We further investigated the Ab50s of mouse and monkey anti-AMA1 IgGs and showed that there were significant differences between the species (mouse, 0.28 mg/ml, and monkey, 0.14 mg/ml, against 3D7 parasites). Although it is unknown whether growth-inhibitory activity in vitro reflects protective immunity in vivo, this study showed that the Ab50 varies with both antigen and species. Our data provide a benchmark for antibody levels for future AMA1- or MSP142-based vaccine development efforts in preclinical and clinical trials.

scholarly journals A chimeric Plasmodium vivax Merozoite Surface Protein Antibody Recognises and Blocks Erythrocytic P. cynomolgi Berok Merozoites In Vitro

2020 ◽  
Author(s):  
Fei-hu Shen ◽  
Jessica Jie Ying Ong ◽  
Yi-fan Sun ◽  
Yao Lei ◽  
Rui-lin Chu ◽  
...  
Keyword(s):  
Growth Inhibition ◽  
Plasmodium Vivax ◽  
Vaccine Candidate ◽  
Surface Protein ◽  
Merozoite Surface Protein ◽  
Surface Proteins ◽  
Vaccine Candidates ◽  
Long Term Culture

Research on erythrocytic Plasmodium vivax merozoite antigens is critical for identifying potential vaccine candidates in reducing vivax disease. However, many P. vivax studies are constrained by its inability to undergo long-term culture in vitro. Conserved across all Plasmodium spp, merozoite surface proteins are essential for invasion into erythrocytes and highly expressed on erythrocytic merozoites, thus making it an ideal vaccine candidate. In clinical trials, the P. vivax merozoite surface protein 1 (PvMSP1-19) vaccine candidate alone has shown to have limited immunogenicity in patients, hence we incorporate the highly conserved and immunogenic C-terminus of both P. vivax merozoite surface protein 8 (PvMSP8) and PvMSP1-19 to develop a multicomponent chimeric protein rPvMSP8+1 for immunization into mice. The resulted chimeric rPvMSP8+1 antibody was shown to recognize native protein MSP8 and MSP1-19 of mature P. vivax schizonts. In the immunized mice, elevated antibody response was observed in the rPvMSP8+1-immunized group as compared to that immunized with single antigen components. In addition, we examined the growth inhibition of these antibodies against P. cynomolgi (Berok strain) parasites, which is phylogenetically close to P. vivax and sustains long term culture in vitro. Similarly, the chimeric anti-rPvMSP8+1 antibodies recognises P. cynomolgi MSP8 and MSP1-19 on mature schizonts, and showed strong inhibition in vitro via growth inhibition assay. This study provides support for a new multi-antigen-based paradigm rPvMSP8+1 to explore potential chimeric vaccine candidates against P. vivax malaria using sister species, P. cynomolgi.

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.

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