Protective Immunity Induced in Squirrel Monkeys with Recombinant Apical Membrane Antigen-1 of Plasmodium fragile

Collins, William E.; Pye, David; Crewther, Pauline E.; Vandenberg, Kirsten; Galland, G. Gale; Sulzer, Alexander J.; Kemp, David J.; Edwards, Stirling; Coppel, Ross L.; Sullivan, JoAnn S.; Morris, Carla L.; Anders, Robin F.

doi:10.4269/ajtmh.1994.51.711

Cited by 159 publications

(92 citation statements)

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“…14,15,[39][40][41][42][43] The finding of diversity in all of these reinforces the difficulties of inducing protective responses capable of transcending strain differences. Immune selection would be consistent with the diversity seen in AMA1, 44 and inefficient antibody responses are elicited to the repeat regions of the other antigens studied.…”

Section: Discussionmentioning

confidence: 98%

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Alterations in Plasmodium falciparum genotypes during sequential infections suggest the presence of strain specific immunity.

Eisen

Saul²,

Fryauff³

et al. 2002

The American Journal of Tropical Medicine and Hygiene

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Abstract. Many of the asexual stage Plasmodium falciparum proteins that are the targets of host protective responses are markedly polymorphic. The full repertoire of diversity is not defined for any antigen. Most studies have focused on the genes encoding merozoite surface proteins 1 and 2 (MSP1, MSP2). We explored the extent of diversity of some of the less studied merozoite surface antigens and analyzed the degree of complexity of malaria field isolates by deriving nucleotide sequences of several antigens. We have determined the genotype of apical membrane antigen 1 (AMA1) in a group of 30 field samples, collected over 29 months, from individuals living in an area of intense malaria transmission in Irian Jaya, identifying 14 different alleles. AMA1 genotyping was combined with previously determined MSP2 typing. AMA1 had the greatest power in distinguishing between isolates but methodological problems, especially when mixed infections are present, suggest it is not an ideal typing target. MSP1, MSP3, and glutamate-rich protein genotypes were also determined from a smaller group of samples, and all results were combined to derive an extended antigenic haplotype. Within this subset of 10 patients, nine different genotypes could be discerned; however, five patients were all infected with the same strain. This strain was present in individuals from two separate villages and was still present 12 months later. This strain was predominant at the first time point but had disappeared at the fourth time point. This significant change in malaria genotypes could be due to strain-specific immunity developing in this population.

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Section: Discussionmentioning

confidence: 98%

“…9 Some proteins such as MSP1, 10,11 MSP2 12 (B. Genton. Swiss Tropical Institute, unpublished data), and AMA1 13,14 have already shown promise as components of an asexual stage vaccine. However, immunity induced by these antigens is, in general, effective only if challenge occurs with a parasite strain expressing an identical sequence.…”

Section: Introductionmentioning

confidence: 99%

Alterations in Plasmodium falciparum genotypes during sequential infections suggest the presence of strain specific immunity.

Eisen

Saul²,

Fryauff³

et al. 2002

The American Journal of Tropical Medicine and Hygiene

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“…Since its initial discovery Ͼ15 years ago, AMA1 has received considerable attention as a malaria vaccine candidate (Deans et al, 1988;Collins et al, 1994;Anders et al, 1998;Kennedy et al, 2002;Stowers et al, 2002). AMA1 proteins are type I transmembrane proteins, with a short C-terminal cytoplasmic tail and a large N-terminal extracellular domain (ectodomain) containing 12-16 conserved cysteine residues (Waters et al, 1990;Hodder et al, 1996;Donahue et al, 2000;Hehl et al, 2000;Gaffar et al, 2004).…”

Section: Introductionmentioning

confidence: 99%

Conditional Expression ofToxoplasma gondiiApical Membrane Antigen-1 (TgAMA1) Demonstrates That TgAMA1 Plays a Critical Role in Host Cell Invasion

Mital

Meissner

Soldati

et al. 2005

MBoC

231

250

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Toxoplasma gondii is an obligate intracellular parasite and an important human pathogen. Relatively little is known about the proteins that orchestrate host cell invasion by T. gondii or related apicomplexan parasites (including Plasmodium spp., which cause malaria), due to the difficulty of studying essential genes in these organisms. We have used a recently developed regulatable promoter to create a conditional knockout of T. gondii apical membrane antigen-1 (TgAMA1). TgAMA1 is a transmembrane protein that localizes to the parasite's micronemes, secretory organelles that discharge during invasion. AMA1 proteins are conserved among apicomplexan parasites and are of intense interest as malaria vaccine candidates. We show here that T. gondii tachyzoites depleted of TgAMA1 are severely compromised in their ability to invade host cells, providing direct genetic evidence that AMA1 functions during invasion. The TgAMA1 deficiency has no effect on microneme secretion or initial attachment of the parasite to the host cell, but it does inhibit secretion of the rhoptries, organelles whose discharge is coupled to active host cell penetration. The data suggest a model in which attachment of the parasite to the host cell occurs in two distinct stages, the second of which requires TgAMA1 and is involved in regulating rhoptry secretion. INTRODUCTIONToxoplasma gondii is one of the one most common protozoan parasites of humans, infecting approximately one-third of the world's population. The disease caused by an acute T. gondii infection, toxoplasmosis, can be life threatening in the congenitally infected fetus and immunocompromised hosts. Like all members of the Phylum Apicomplexa, including Plasmodium spp. (the causative agents of malaria) and Cryptosporidium parvum (a significant worldwide cause of waterborne illness), T. gondii is an obligate intracellular parasite. Host cell invasion is a critical step in the pathogenesis of the diseases caused by apicomplexan parasites, including toxoplasmosis. T. gondii represents an excellent model system for studying the relatively conserved process of apicomplexan invasion, because of the ease with which this parasite can be cultured and genetically manipulated (Roos et al., 1994;Black and Boothroyd, 2000;Kim and Weiss, 2004).Host cell invasion by apicomplexan parasites is a complex, multistep process (reviewed in Black and Boothroyd, 2000;Chitnis and Blackman, 2000). In T. gondii, the asexual stage tachyzoites move over solid surfaces, including cells, by an unusual form of substrate-dependent gliding motility (Sibley et al., 1998;Hakansson et al., 1999). After the apical end of a parasite comes in contact with the host cell membrane, apical secretory organelles (micronemes and rhoptries) sequentially discharge their contents (Dubremetz et al., 1993;Carruthers and Sibley, 1997) and a zone of tight interaction forms between the two cells (Nichols and O'Connor, 1981;Dubremetz et al., 1985;Grimwood and Smith, 1995). An invagination in the host cell plasma membrane develops at the point ...

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“…After repeated exposures, naturally acquired immunity against malaria could develop, predominantly targeting the blood-stage parasites (11). In immunization studies using animal models, a protective immune response is elicited when animals were immunized with blood-stage antigens, particularly merozoite antigens (12,13). Therefore merozoite proteins, either located within the apical organelles or on the merozoite surface, are the leading blood-stage vaccine candidates.…”

Section: Introductionmentioning

confidence: 99%

Immunogenicity of the Merozoite Surface Protein-1 (Msp-1) of Human Plasmodium Sp.

Yl¹,

Fw²,

My³

2015

JUMMEC

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Malaria is a major cause of mortality and morbidity globally. Great efforts have been made in the prevention and the elimination of malaria, especially in controlling the malaria vector, the mosquito. Another promising approach would be the development of malaria vaccines. Malaria vaccine studies can be focused on the pre-erythrocytic-stage antigens and the blood-stage antigens, and on the transmission blocking agents targeting the malaria gametocytes. The blood-stage antigens are the leading candidates in malaria vaccine development, as the blood-stage parasites are responsible for causing symptomatic malaria. Human acquired immunity largely targets on blood-stage antigens. This review focuses on one of the most extensively studied blood-stage antigen, the merozoite surface protein-1 (MSP-1), specifically on its evaluation and immunogenicity in rodents and primate models, and its safety and immunogenicity in human clinical trials.

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Protective Immunity Induced in Squirrel Monkeys with Recombinant Apical Membrane Antigen-1 of Plasmodium fragile

Cited by 159 publications

References 0 publications

Alterations in Plasmodium falciparum genotypes during sequential infections suggest the presence of strain specific immunity.

Alterations in Plasmodium falciparum genotypes during sequential infections suggest the presence of strain specific immunity.

Conditional Expression ofToxoplasma gondiiApical Membrane Antigen-1 (TgAMA1) Demonstrates That TgAMA1 Plays a Critical Role in Host Cell Invasion

Immunogenicity of the Merozoite Surface Protein-1 (Msp-1) of Human Plasmodium Sp.

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