Immunization against Plasmodium chabaudi malaria using combined formulations of apical membrane antigen-1 and merozoite surface protein-1

Burns, James M.; Flaherty, Patrick R.; Romero, Margarita; Weidanz, William P.

doi:10.1016/s0264-410x(03)00026-4

Cited by 26 publications

(39 citation statements)

References 43 publications

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“…Our inability to correlate PyMSP-8-induced protection with the isotype of Ag-specific Abs is consistent with several active and passive immunization studies in the P. yoelii and P. chabaudi models involving MSP-1 and AMA-1 (19,20,49,50). The conclusion from these studies was that Ab-mediated neutralization of extracellular merozoites was IgG isotype and Fc receptor independent.…”

Section: Discussionsupporting

confidence: 89%

“…In contrast, cytophilic IgG1 and IgG3 Abs have been repeatedly correlated with protection against P. falciparum malaria in human subjects (51)(52)(53). Recently, passive protection mediated by a human IgG1 Ab specific for P. falciparum MSP-1 19 was shown to require the expression of Fc␥RI, presumably on macrophages, in a model system that combined Fc receptor transgenic mice and P. falciparum-Plasmodium berghei chimeric parasites (54). The corresponding cytophilic isotype in mice, IgG2a/c, has also been associated with protection in studies of vaccine-induced and infection-induced responses in the P. yoelii (55)(56)(57)(58) and P. chabaudi (58 -59) models.…”

Section: Discussionmentioning

confidence: 99%

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Suppression of LethalPlasmodium yoeliiMalaria following Protective Immunization Requires Antibody-, IL-4-, and IFN-γ-Dependent Responses Induced by Vaccination and/or Challenge Infection

Petritus

Burns

2008

The Journal of Immunology

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Immunization with Plasmodium yoelii merozoite surface protein (PyMSP)-8 protects mice from lethal malaria but does not prevent infection. Using this merozoite surface protein-based vaccine model, we investigated vaccine- and infection-induced immune responses that contribute to protection. Analysis of prechallenge sera from rPyMSP-8-immunized C57BL/6 and BALB/c mice revealed high and comparable levels of Ag-specific IgG, but differences in isotype profile and specificity for conformational epitopes were noted. As both strains of mice were similarly protected against P. yoelii, we could not correlate vaccine-induced responses with protection. However, passive immunization studies suggested that protection resulted from differing immune responses. Studies with cytokine-deficient mice showed that protection was induced by immunization of C57BL/6 mice only when IL-4 and IFN-γ were both present. In BALB/c mice, the absence of either IL-4 or IFN-γ led to predictable shifts in the IgG isotype profile but did not reduce the magnitude of the Ab response induced by rPyMSP-8 immunization. Immunized IL-4−/− BALB/c mice were solidly protected against P. yoelii. To our surprise, immunized IFN-γ−/− BALB/c mice initially controlled parasite growth but eventually succumbed to infection. Analysis of cytokine production revealed that P. yoelii infection induced two distinct peaks of IFN-γ that correlated with periods of controlled parasite growth in intact, rPyMSP-8-immunized BALB/c mice. Maximal parasite growth occurred during a period of sustained TGF-β production. Combined, the data indicate that induction of protective responses by merozoite surface protein-based vaccines depends on IL-4 and IFN-γ-dependent pathways and that vaccine efficacy is significantly influenced by host responses elicited upon infection.

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Section: Discussionsupporting

confidence: 89%

Section: Discussionmentioning

confidence: 99%

Suppression of LethalPlasmodium yoeliiMalaria following Protective Immunization Requires Antibody-, IL-4-, and IFN-γ-Dependent Responses Induced by Vaccination and/or Challenge Infection

Petritus

Burns

2008

The Journal of Immunology

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“…Thus these animals were most likely non-responsive to immunization, and this makes it difficult to draw firm conclusions on the effectiveness of the AM fusion protein candidate in this study. Parasite inhibition studies done in vitro with antibodies raised in rabbits as well as challenge studies in mice have however shown that vaccines composed of AMA1 and MSP1 either as a mixture or a fusion protein product induced functional antibodies [35,36,54]. …”

Section: Discussionmentioning

confidence: 99%

“…IgG responses to Pf AMA1 alone or the Pf AMA1/ Pf MSP1 19 vaccine products showed signs of strain specificity in functional assays, while responses to products containing Pf MSP1 19 alone showed limited strain-specificity [35]. Challenge studies in rodents immunized with a cocktail of Plasmodium chabaudi AMA1 and MSP1 42 antigens also showed a greater reduction in peak parasitaemia compared to separate immunizations with the single antigens [36]. Another study involving a combination vaccine that consists of Pf AMA1 and Pf MSP1 42 yielded responses that were directed against both antigens, though protection induced by the combination vaccine was not superior to that induced by the Pf AMA1 vaccine alone [27].…”

Section: Introductionmentioning

confidence: 99%

Safety and immunogenicity of multi-antigen AMA1-based vaccines formulated with CoVaccine HT™ and Montanide ISA 51 in rhesus macaques

Kusi

Remarque

Riasat

et al. 2011

Malar J

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BackgroundIncreasing the breadth of the functional antibody response through immunization with Plasmodium falciparum apical membrane antigen 1 (PfAMA1) multi-allele vaccine formulations has been demonstrated in several rodent and rabbit studies. This study assesses the safety and immunogenicity of three PfAMA1 Diversity-Covering (DiCo) vaccine candidates formulated as an equimolar mixture (DiCo mix) in CoVaccine HT™ or Montanide ISA 51, as well as that of a PfAMA1-MSP119 fusion protein formulated in Montanide ISA 51.MethodsVaccine safety in rhesus macaques was monitored by animal behaviour observation and assessment of organ and systemic functions through clinical chemistry and haematology measurements. The immunogenicity of vaccine formulations was assessed by enzyme-linked immunosorbent assays and in vitro parasite growth inhibition assays with three culture-adapted P. falciparum strains.ResultsThese data show that both adjuvants were well tolerated with only transient changes in a few of the chemical and haematological parameters measured. DiCo mix formulated in CoVaccine HT™ proved immunologically and functionally superior to the same candidate formulated in Montanide ISA 51. Immunological data from the fusion protein candidate was however difficult to interpret as four out of six immunized animals were non-responsive for unknown reasons.ConclusionsThe study highlights the safety and immunological benefits of DiCo mix as a potential human vaccine against blood stage malaria, especially when formulated in CoVaccine HT™, and adds to the accumulating data on the specificity broadening effects of DiCo mix.

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“…The isotypic profile of the antigen-specific antibodies in the sera of infected mice depleted of NK or ␥␦ T cells and their controls was determined by enzyme-linked immunosorbent assay (ELISA) using P. chabaudi apical membrane antigen-1 (rPCAMA-1)-or P. chabaudi merozoite surface protein-1 42 (rPCMSP-1)-coated wells as described previously (5). Briefly, serum from each animal harvested day 19 p.i.…”

Section: Parasites and Infections Of Mice Ccr2mentioning

confidence: 99%

γδ T Cells but Not NK Cells Are Essential for Cell-Mediated Immunity against Plasmodium chabaudi Malaria

et al. 2010

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Immunization against Plasmodium chabaudi malaria using combined formulations of apical membrane antigen-1 and merozoite surface protein-1

Cited by 26 publications

References 43 publications

Suppression of LethalPlasmodium yoeliiMalaria following Protective Immunization Requires Antibody-, IL-4-, and IFN-γ-Dependent Responses Induced by Vaccination and/or Challenge Infection

Suppression of LethalPlasmodium yoeliiMalaria following Protective Immunization Requires Antibody-, IL-4-, and IFN-γ-Dependent Responses Induced by Vaccination and/or Challenge Infection

Safety and immunogenicity of multi-antigen AMA1-based vaccines formulated with CoVaccine HT™ and Montanide ISA 51 in rhesus macaques

γδ T Cells but Not NK Cells Are Essential for Cell-Mediated Immunity against Plasmodium chabaudi Malaria

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