Passive transfer of growth-inhibitory antibodies raised against yeast-expressed recombinant Plasmodium falciparum merozoite surface protein-1(19).

Gozalo, Alfonso S; Lucas, Carmen; Cachay, Marlene I.; Wellde, B. T.; Hall, Ted; Bell, Brian A.; Wood, James F.; Watts, Douglas M.; Wooster, M. T.; Lyon, Jeffrey A.; Moch, J. Kathleen; Haynes, J. David; Williams, Jon H Sims; Holland, Carolyn A.; Watson, E.D.; Kester, Kent E.; Kaslow, David C.; Ballou, W. Ripley

doi:10.4269/ajtmh.1998.59.991

Cited by 12 publications

(5 citation statements)

References 14 publications

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“…We observed that of the four mice that received both T cells and rabbit anti-AMA1 antiserum, only one animal (mouse 2) developed a significant murine anti-AMA1 response. The transfused Abs may have suppressed the development of such a response, as was shown to occur in a different malaria system (25,26). The combination in nude mice of this passively administered CMI response with a passively administered anti-AMA1 Ab response gives rise to a degree of protection similar to that which follows AMA1 vaccination of euthymic mice (Fig.…”

Section: Discussionmentioning

confidence: 85%

CD4+ T Cells Acting Independently of Antibody Contribute to Protective Immunity to Plasmodium chabaudi Infection After Apical Membrane Antigen 1 Immunization

Hodder

Yan

et al. 2000

The Journal of Immunology

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Apical membrane Ag 1 (AMA1) is a leading malaria vaccine candidate. Homologues of AMA1 can induce protection in mice and monkeys, but the mechanism of immunity is not understood. Mice immunized with a refolded, recombinant, Plasmodium chabaudi AMA1 fragment (AMA1B) can withstand subsequent challenge with P. chabaudi adami. Here we show that CD4+ T cell depletion, but not γδ T cell depletion, can cause a significant drop in antiparasite immunity in either immunized normal or immunized B cell KO mice. In normal mice, this loss of immunity is not accompanied by a decline in Ab levels. These observations indicate a role for AMA1-specific Ab-independent T cell-mediated immunity. However, the loss of immunity in normal CD4+ T cell-depleted mice is temporary. Furthermore, immunized B cell KO mice cannot survive infection, demonstrating the absolute importance of B cells, and presumably Ab, in AMA1-induced immunity. CD4+ T cells specific for a cryptic conserved epitope on AMA1 can adoptively transfer protection to athymic (nu/nu) mice, the level of which is enhanced by cotransfer of rabbit anti-AMA1-specific antisera. Recipients of rabbit antisera alone do not survive. Some protected recipients of T cells plus antisera do not develop their own AMA 1-specific Ab response, suggesting that AMA 1-specific CMI alone can protect mice. These data are the first to demonstrate the specificity of any protective CMI response in malaria and have important implications for developing a malaria vaccine.

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Section: Discussionmentioning

confidence: 85%

CD4+ T Cells Acting Independently of Antibody Contribute to Protective Immunity to Plasmodium chabaudi Infection After Apical Membrane Antigen 1 Immunization

Hodder

Yan

et al. 2000

The Journal of Immunology

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“…Recombinant MSP-1 19 proteins corresponding to the four major described variants of MSP-1 19 (the Wellcome/K1 (E-TSR) and MAD20 (Q-KNG) alleles as well as the E-KNG and Q-TSR variants) were expressed in Saccharomyces cerivisiae (39), obtained from the Malaria Research and Reference Reagent Resource Center (Manassas, VA). The Wellcome/K1 and MAD20 alleles were also expressed in Escherichia coli as GST fusion proteins (40).…”

Section: Laboratory Studiesmentioning

confidence: 99%

Evidence That Invasion-Inhibitory Antibodies Specific for the 19-kDa Fragment of Merozoite Surface Protein-1 (MSP-119) Can Play a Protective Role against Blood-Stage Plasmodium falciparum Infection in Individuals in a Malaria Endemic Area of Africa

John

O’Donnell

Sumba

et al. 2004

The Journal of Immunology

145

157

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The C-terminal 19-kDa fragment of Plasmodium falciparum merozoite surface protein-1 (MSP-119) is a target of protective Abs against blood-stage infection and a leading candidate for inclusion in a human malaria vaccine. However, the precise role, relative importance, and mechanism of action of Abs that target this protein remain unclear. To examine the potential protective role of Abs to MSP-119 in individuals naturally exposed to malaria, we conducted a treatment time to infection study over a 10-wk period in 76 residents of a highland area of western Kenya during a malaria epidemic. These semi-immune individuals were not all equally susceptible to reinfection with P. falciparum following drug cure. Using a new neutralization assay based on transgenic P. falciparum expressing the P. chabaudi MSP-119 orthologue, individuals with high-level MSP-119-specific invasion-inhibitory Abs (>75th percentile) had a 66% reduction in the risk of blood-stage infection relative to others in the population (95% confidence interval, 3–88%). In contrast, high levels of MSP-119 IgG or IgG subclass Abs measured by enzyme immunoassay with six different recombinant MSP-119 Ags did not correlate with protection from infection. IgG Abs measured by serology and functional invasion-inhibitory activity did not correlate with each other. These findings implicate an important protective role for MSP-119-specific invasion inhibitory Abs in immunity to blood-stage P. falciparum infection, and suggest that the measurement of MSP-119 specific inhibitory Abs may serve as an accurate correlate of protection in clinical trials of MSP-1-based vaccines.

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“…This protection is largely antibody mediated (18,36). Aotus monkeys were protected from the virulent FVO strain of P. falciparum by immunization with MSP1 19 (12,15,34). MSP1 19 -specific antibodies confer passive immunity in rodent models (4,53) and inhibit merozoite invasion in vitro (2).…”

mentioning

confidence: 99%

Malaria Vaccine-Related Benefits of a Single Protein ComprisingPlasmodium falciparumApical Membrane Antigen 1 Domains I and II Fused to a Modified Form of the 19-Kilodalton C-Terminal Fragment of Merozoite Surface Protein 1

Faber

Remarque

Morgan³

et al. 2007

Infect Immun

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We show that the smallest module of Plasmodium falciparum AMA1 (PfAMA1) that can be expressed in the yeast Pichia pastoris while retaining the capacity to induce high levels of parasite-inhibitory antibodies comprises domains I and II. Based on this, two fusion proteins, differing in the order of the modules, were The annual malaria burden of 300 to 500 million clinical cases results in an estimated mortality for up to 2 million people, predominantly sub-Saharan African children under 5 years of age (52). A malaria vaccine would make a significant contribution to reducing the enormous socioeconomic burden caused by this disease. A number of vaccine approaches, targeting various stages of the complex parasite life cycle, are being investigated (21). Apical membrane antigen 1 (AMA1) and merozoite surface protein 1 (MSP1) are potential vaccine components, and a number of vaccines using elements of these molecules are currently in early clinical evaluation. Previous research has indicated that a combination of MSP1 and AMA1 has vaccine-related advantages over either antigen alone (3, 55). Both molecules are essential components of the asexual blood-stage merozoite (50, 60), the developmental stage of the parasite stage responsible for invasion of erythrocytes. They are also both present on merozoites that emerge from infected liver cells, and AMA1 has also been identified as a sporozoite protein (51). Plasmodium falciparum AMA1 (PfAMA1) is a polymorphic protein; over 10% of its amino acid residues can change without obvious effects on its function in invasion. With few exceptions, polymorphic residues are bi-or trimorphic, and all are located on the outside of the molecule, predominantly on one face (47). One strategy to tackle any potential negative effect of polymorphism in vaccine development is to combine PfAMA1 with other targets that are not, or are less, polymorphic, such as MSP1 19 (59). A single-protein vaccine has cost, speed, and potential functionality benefits compared with vaccines prepared from mixtures of proteins. We have therefore investigated how minimal elements of AMA1 and MSP1, each retaining the ability to induce growth-inhibitory antibodies, can be incorporated into fusion proteins that allow the development of single-protein, multitarget malaria vaccines.Micronemes are organelles of the merozoite apical complex, a structure intimately associated with the invasion of erythrocytes. AMA1 is initially trafficked to micronemes as an 83-kDa type 1 integral membrane protein; subsequently, the N-terminal prodomain is proteolytically cleaved prior to relocalization to the merozoite outer membrane (43). Further cleavage, proximal to the transmembrane region, then releases the ectodomain from the parasite surface (26). AMA1 contains 16 conserved cysteine residues that form eight intramolecular disulfide bonds (20). The recently elucidated three-dimensional structure of AMA1 (47) confirms that after cleavage of the prodomain, the ectodomain essentially comprises three interacting domains (DI, DII, and D...

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Passive transfer of growth-inhibitory antibodies raised against yeast-expressed recombinant Plasmodium falciparum merozoite surface protein-1(19).

Cited by 12 publications

References 14 publications

CD4+ T Cells Acting Independently of Antibody Contribute to Protective Immunity to Plasmodium chabaudi Infection After Apical Membrane Antigen 1 Immunization

CD4+ T Cells Acting Independently of Antibody Contribute to Protective Immunity to Plasmodium chabaudi Infection After Apical Membrane Antigen 1 Immunization

Evidence That Invasion-Inhibitory Antibodies Specific for the 19-kDa Fragment of Merozoite Surface Protein-1 (MSP-119) Can Play a Protective Role against Blood-Stage Plasmodium falciparum Infection in Individuals in a Malaria Endemic Area of Africa

Malaria Vaccine-Related Benefits of a Single Protein ComprisingPlasmodium falciparumApical Membrane Antigen 1 Domains I and II Fused to a Modified Form of the 19-Kilodalton C-Terminal Fragment of Merozoite Surface Protein 1

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