Antigenic and sequence diversity at the C-terminus of the merozoite surface protein-1 from rodent malaria isolates, and the binding of protective monoclonal antibodies

Benjamin, Pearline A; Ling, Irene T.; Clottey, George; Spencer, Lilian M.; Ogun, Solabomi A.; Fleck, Suzanne L.; Walliker, David; Morgan, W. T. J.; Birdsall, B.; Feeney, J.; Holder, Anthony A.

doi:10.1016/s0166-6851(99)00142-5

Cited by 16 publications

(15 citation statements)

References 36 publications

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“…P. yoelii MSP1 19 is highly diverse across strains [51, 71, 72]. P. yoelii nigeriensis N67 differs in a total of 22 amino acid residues in comparison to the P. yoelii 17XNL reported sequence included in the PyRMC-MSP1 19 , 9 in the first EGF domain, 3 in the joining region, and 10 in the second EGF domain [72]. Consistent with the extensive variability in this region, immunization with a GST fusion protein expressing PyMSP1 19 induced protection against the homologous but not heterologous strain [51].…”

Section: Discussionmentioning

confidence: 99%

Genetic linkage of autologous T cell epitopes in a chimeric recombinant construct improves anti-parasite and anti-disease protective effect of a malaria vaccine candidate

Singh

Cabrera-Mora

Jiang

et al. 2010

Vaccine

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We have reported the design of polyvalent synthetic and recombinant chimeras that include promiscuous T cell epitopes as a viable delivery system for pre-erythrocytic subunit malaria vaccines. To further assess the ability of several Plasmodium T cell epitopes to enhance vaccine potency, we designed a synthetic gene encoding four P. yoelii merozoite surface protein 1 (PyMSP1) CD4 + promiscuous T cell epitopes fused in tandem to the homologous carboxyl terminal PyMSP1 19 fragment. This Recombinant Modular Chimera (PyRMC-MSP1 19 ) was tested for immunogenicity and protective efficacy in comparative experiments with a recombinant protein expressing only the PyMSP1 19 fragment. Both proteins induced comparable antibody responses. However PyRMC-MSP1 19 elicited higher anti-parasite antibody titers and more robust protection against both hyperparasitemia and malarial anemia. Most importantly, passive transfer of anti-PyRMC-MSP1 19 , but not anti-PyMSP1 19 antibodies protected against heterologous challenge. These studies show that protective efficacy can be significantly improved by inclusion of an array of autologous promiscuous T cell epitopes in vaccine constructs.

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Section: Discussionmentioning

confidence: 99%

Genetic linkage of autologous T cell epitopes in a chimeric recombinant construct improves anti-parasite and anti-disease protective effect of a malaria vaccine candidate

Singh

Cabrera-Mora

Jiang

et al. 2010

Vaccine

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“…Since the challenge with the P. falciparum FVO allele results in higher protection in the FVOvaccinated Aotus monkeys compared to the 3D7 MSP-1 19 vaccinated group (24), we hypothesize that a conserved difference at the E 14 position between PcMSP-1 19 and PvMSP-1 19 was critical for allowing cross-species protection seen in this study. The A 38 corresponding residue in PyMSP-1 19 is G; an inhibitory MAb, G3, failed to bind PyMSP-1 19 from isolates that had a nonconservative change, N, at this position (5). We speculate that a conserved amino acid difference, A 38 -G, at this position may also be critical for allowing cross-protection in this study.…”

Section: Discussionmentioning

confidence: 64%

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

et al. 2005

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The 42-kDa fragment of the merozoite surface protein 1 (MSP-1 42 ) 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-1 42 (PvMSP-1 42 ) 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-1 42 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-1 42 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-1 42 (PcMSP-1 42 ) proteins. All proteins induced equally high-titer, cross-reacting antibodies. Upon challenge with P. cynomolgi, none of the MSP-1 42 -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-1 42 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-1 42 and PvMSP-1 42 proteins also appeared to have a similar partially protective effect.Progress towards a vaccine against Plasmodium falciparum malaria is advancing rapidly, with several candidate antigens being tested for safety and efficacy in humans (4); comparatively, however, the development of a vaccine against P. vivax malaria has lagged behind. Unlike P. falciparum, where sporozoite challenge studies using the chloroquine-sensitive 3D7 strain are available, the relapsing nature of P. vivax hepatic stages and the lack of an in vitro culture system precludes any sporozoite challenge studies of P. vivax vaccine candidates in humans. Therefore, as more recombinant vaccine products become available, there will be an increasing need to compare and down-select vaccine candidate antigens in preclinical studies using animal models of P. vivax infection.P. cynomolgi, which infects rhesus macaques in southeast Asia, is a closely related species to P. vivax; human transmission of P. cynomolgi has also been reported (25). The two parasites share a similar clinical course of infection (26), a reticulocyte-specific invasion (17), the presence of Schuffner's dots on infected erythrocytes (2), and a dormant liver hypnozoite stage that is responsible for a relapsing blood stage infection (23). P. cynomolgi and P. ...

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“…Both B6 and F5 bind to an epitope within the first EGF-like domain of P. yoelii MSP-1 19 , whereas D3 binds to an epitope in the longer MSP1 42 fragment, which is formed from the two subdomains of MSP1 33 and MSP1 19 [5]. The epitopes binding B6 and F5 overlap but are not identical [5,11], but their proximity to the epitope of D3 is unclear since the epitope for this antibody appears to be a conformational epitope that is formed only in the intact MSP-1 42 . In the first step of this study, the minimum protective dose (MPD) was determined for each antibody as 0.6, 0.9 and 1.2 mg for mAbs D3, B6 and F5, respectively.…”

Section: Discussionmentioning

confidence: 99%

Suppressive and additive effects in protection mediated by combinations of monoclonal antibodies specific for merozoite surface protein 1 of Plasmodium yoelii

Eslava

Payares

Pernia

et al. 2010

Malar J

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BackgroundThe merozoite surface protein (MSP)-1 is a target antigen of protective immunity and a malaria vaccine candidate. The nature of this protective immune response warrants further investigation: although specific antibody is thought to play a major role, the mechanisms of protection are still unclear. Monoclonal antibodies (mAbs) specific for the C-terminus of MSP-1 from Plasmodium yoelii have been shown previously to provide protection against challenge infection when administered by passive immunization to mice. Three protective mAbs were re-examined and, in particular, the effect of combinations of antibodies on the protection provided was studied. It was found that a combination of two antibodies can either provide additive protective effects or result in a suppression of protection. In this report the importance of antibody subclass and epitope specificity in the outcome of these passive immunization experiments are discussed.MethodsThe minimum protective dose (MPD) for each mAb was determined, and then combinations of antibody at their MPD were investigated for their ability to control parasitaemia and promote survival in groups of mice. Mice were inoculated over three days with the MPD and challenged with a blood stage infection of the virulent P. yoelii 17 XL. The resultant parasitaemia was assessed daily on Giemsa-stained blood films. Following the infection the presence of MSP-1 specific antibodies in the sera was monitored, and the proliferative responses of cells in the spleen of protected mice were measured.ResultsCombining antibodies resulted in either an additive effect on protection, with reduced peak parasitaemia and better survival, or resulted in a suppression of protection over that achieved by a single antibody alone. An additive effect was observed when B6 and F5 that have the same isotype and similar fine specificity, were combined. However, a combination of mAb D3, an IgG2a, with either B6 or F5 (both IgG3) suppressed protection, an effect that may have been due to the combination of different isotypes or to the different fine specificity of the antibodies.ConclusionsThese results suggest that a combination of protective antibodies with either the same or different isotypes can produce either an additive or a suppressive effect in passive immunization. This phenomenon may be important in better understanding immunity in this experimental mouse model of malaria.

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Antigenic and sequence diversity at the C-terminus of the merozoite surface protein-1 from rodent malaria isolates, and the binding of protective monoclonal antibodies

Cited by 16 publications

References 36 publications

Genetic linkage of autologous T cell epitopes in a chimeric recombinant construct improves anti-parasite and anti-disease protective effect of a malaria vaccine candidate

Genetic linkage of autologous T cell epitopes in a chimeric recombinant construct improves anti-parasite and anti-disease protective effect of a malaria vaccine candidate

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

Suppressive and additive effects in protection mediated by combinations of monoclonal antibodies specific for merozoite surface protein 1 of Plasmodium yoelii

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