The Experts below are selected from a list of 75 Experts worldwide ranked by ideXlab platform
Elizabeth Nardin - One of the best experts on this subject based on the ideXlab platform.
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cutting edge a new tool to evaluate human pre erythrocytic malaria vaccines rodent parasites bearing a hybrid plasmodium falciparum circumsporozoite Protein
Journal of Immunology, 2002Co-Authors: Cathrine Persson, Victor Nussenzweig, Giane A Oliveira, Ali A Sultan, Purnima Bhanot, Elizabeth NardinAbstract:Malaria vaccines containing the Plasmodium falciparum Circumsporozoite Protein Repeat domain are undergoing human trials. There is no simple method to evaluate the effect of vaccine-induced responses on P. falciparum sporozoite infectivity. Unlike the rodent malaria Plasmodium berghei, P. falciparum sporozoites do not infect common laboratory animals and only develop in vitro in human hepatocyte cultures. We generated a recombinant P. berghei parasite bearing P. falciparum Circumsporozoite Protein Repeats. These hybrid sporozoites are fully infective in vivo and in vitro. Monoclonal and polyclonal Abs to P. falciparum Repeats neutralize hybrid parasite infectivity, and mice immunized with a P. falciparum vaccine are protected against challenge with hybrid sporozoites.
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synthetic malaria peptide vaccine elicits high levels of antibodies in vaccinees of defined hla genotypes
The Journal of Infectious Diseases, 2000Co-Authors: Elizabeth Nardin, Giane A Oliveira, Mauricio J Calvocalle, Rosa Moya Z Castro, Ruth S Nussenzweig, B J Schmeckpeper, Fenton B Hall, Carter L Diggs, Sacared A Bodison, Robert R EdelmanAbstract:A multiple antigen peptide (MAP) malaria vaccine containing minimal Plasmodium falciparum circumsporozoite Protein Repeat epitopes was assessed for safety and immunogenicity in volunteers of known class II genotypes. The MAP/alum/QS-21 vaccine formulation elicited high levels of parasite-specific antibodies in 10 of 12 volunteers expressing DQB1*0603, DRB1*0401, or DRB1*1101 class II molecules. In contrast, volunteers of other HLA genotypes were low responders or nonresponders. A second study of 7 volunteers confirmed the correlation of class II genotype and high responder phenotype. This is the first demonstration in humans that a peptide vaccine containing minimal T and B cell epitopes composed of only 5 amino acids (N, A, V, D, and P) can elicit antibody titers comparable to multiple exposures to irradiated P. falciparum-infected mosquitoes. Moreover, the high-responder phenotypes were predicted by analysis of peptide/HLA interactions in vitro, thus facilitating the rational design of epitope-based peptide vaccines for malaria, as well as for other pathogens.
Zoltan Beck - One of the best experts on this subject based on the ideXlab platform.
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optimization of a plasmodium falciparum circumsporozoite Protein Repeat vaccine using the tobacco mosaic virus platform
Proceedings of the National Academy of Sciences of the United States of America, 2020Co-Authors: Mark D Langowski, Farhat Khan, Alexis A Bitzer, Christopher J Genito, Andrew J Schrader, Monica L Martin, Kimberly Soto, Sri Hadiwidjojo, Zoltan BeckAbstract:Plasmodium falciparum vaccine RTS,S/AS01 is based on the major NPNA Repeat and the C-terminal region of the circumsporozoite Protein (CSP). RTS,S-induced NPNA-specific antibody titer and avidity have been associated with high-level protection in naive subjects, but efficacy and longevity in target populations is relatively low. In an effort to improve upon RTS,S, a minimal Repeat-only, epitope-focused, protective, malaria vaccine was designed. Repeat antigen copy number and flexibility was optimized using the tobacco mosaic virus (TMV) display platform. Comparing antigenicity of TMV displaying 3 to 20 copies of NPNA revealed that low copy number can reduce the abundance of low-affinity monoclonal antibody (mAb) epitopes while retaining high-affinity mAb epitopes. TMV presentation improved titer and avidity of Repeat-specific Abs compared to a nearly full-length Protein vaccine (FL-CSP). NPNAx5 antigen displayed as a loop on the TMV particle was found to be most optimal and its efficacy could be further augmented by combination with a human-use adjuvant ALFQ that contains immune-stimulators. These data were confirmed in rhesus macaques where a low dose of TMV-NPNAx5 elicited Abs that persisted at functional levels for up to 11 mo. We show here a complex association between NPNA copy number, flexibility, antigenicity, immunogenicity, and efficacy of CSP-based vaccines. We hypothesize that designing minimal epitope CSP vaccines could confer better and more durable protection against malaria. Preclinical data presented here supports the evaluation of TMV-NPNAx5/ALFQ in human trials.
Giane A Oliveira - One of the best experts on this subject based on the ideXlab platform.
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cutting edge a new tool to evaluate human pre erythrocytic malaria vaccines rodent parasites bearing a hybrid plasmodium falciparum circumsporozoite Protein
Journal of Immunology, 2002Co-Authors: Cathrine Persson, Victor Nussenzweig, Giane A Oliveira, Ali A Sultan, Purnima Bhanot, Elizabeth NardinAbstract:Malaria vaccines containing the Plasmodium falciparum Circumsporozoite Protein Repeat domain are undergoing human trials. There is no simple method to evaluate the effect of vaccine-induced responses on P. falciparum sporozoite infectivity. Unlike the rodent malaria Plasmodium berghei, P. falciparum sporozoites do not infect common laboratory animals and only develop in vitro in human hepatocyte cultures. We generated a recombinant P. berghei parasite bearing P. falciparum Circumsporozoite Protein Repeats. These hybrid sporozoites are fully infective in vivo and in vitro. Monoclonal and polyclonal Abs to P. falciparum Repeats neutralize hybrid parasite infectivity, and mice immunized with a P. falciparum vaccine are protected against challenge with hybrid sporozoites.
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synthetic malaria peptide vaccine elicits high levels of antibodies in vaccinees of defined hla genotypes
The Journal of Infectious Diseases, 2000Co-Authors: Elizabeth Nardin, Giane A Oliveira, Mauricio J Calvocalle, Rosa Moya Z Castro, Ruth S Nussenzweig, B J Schmeckpeper, Fenton B Hall, Carter L Diggs, Sacared A Bodison, Robert R EdelmanAbstract:A multiple antigen peptide (MAP) malaria vaccine containing minimal Plasmodium falciparum circumsporozoite Protein Repeat epitopes was assessed for safety and immunogenicity in volunteers of known class II genotypes. The MAP/alum/QS-21 vaccine formulation elicited high levels of parasite-specific antibodies in 10 of 12 volunteers expressing DQB1*0603, DRB1*0401, or DRB1*1101 class II molecules. In contrast, volunteers of other HLA genotypes were low responders or nonresponders. A second study of 7 volunteers confirmed the correlation of class II genotype and high responder phenotype. This is the first demonstration in humans that a peptide vaccine containing minimal T and B cell epitopes composed of only 5 amino acids (N, A, V, D, and P) can elicit antibody titers comparable to multiple exposures to irradiated P. falciparum-infected mosquitoes. Moreover, the high-responder phenotypes were predicted by analysis of peptide/HLA interactions in vitro, thus facilitating the rational design of epitope-based peptide vaccines for malaria, as well as for other pathogens.
Cathrine Persson - One of the best experts on this subject based on the ideXlab platform.
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cutting edge a new tool to evaluate human pre erythrocytic malaria vaccines rodent parasites bearing a hybrid plasmodium falciparum circumsporozoite Protein
Journal of Immunology, 2002Co-Authors: Cathrine Persson, Victor Nussenzweig, Giane A Oliveira, Ali A Sultan, Purnima Bhanot, Elizabeth NardinAbstract:Malaria vaccines containing the Plasmodium falciparum Circumsporozoite Protein Repeat domain are undergoing human trials. There is no simple method to evaluate the effect of vaccine-induced responses on P. falciparum sporozoite infectivity. Unlike the rodent malaria Plasmodium berghei, P. falciparum sporozoites do not infect common laboratory animals and only develop in vitro in human hepatocyte cultures. We generated a recombinant P. berghei parasite bearing P. falciparum Circumsporozoite Protein Repeats. These hybrid sporozoites are fully infective in vivo and in vitro. Monoclonal and polyclonal Abs to P. falciparum Repeats neutralize hybrid parasite infectivity, and mice immunized with a P. falciparum vaccine are protected against challenge with hybrid sporozoites.
Traci Tanaka M Hall - One of the best experts on this subject based on the ideXlab platform.
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rna regulatory networks diversified through curvature of the puf Protein scaffold
Nature Communications, 2015Co-Authors: Daniel Wilinski, Traci Tanaka M Hall, Chen Qiu, Christopher P Lapointe, Markus Nevil, Zachary T Campbell, Marvin WickensAbstract:Proteins bind and control mRNAs, directing their localization, translation and stability. Members of the PUF family of RNA-binding Proteins control multiple mRNAs in a single cell, and play key roles in development, stem cell maintenance and memory formation. Here we identified the mRNA targets of a S. cerevisiae PUF Protein, Puf5p, by ultraviolet-crosslinking-affinity purification and high-throughput sequencing (HITS-CLIP). The binding sites recognized by Puf5p are diverse, with variable spacer lengths between two specific sequences. Each length of site correlates with a distinct biological function. Crystal structures of Puf5p–RNA complexes reveal that the Protein scaffold presents an exceptionally flat and extended interaction surface relative to other PUF Proteins. In complexes with RNAs of different lengths, the Protein is unchanged. A single PUF Protein Repeat is sufficient to induce broadening of specificity. Changes in Protein architecture, such as alterations in curvature, may lead to evolution of mRNA regulatory networks.
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basis of altered rna binding specificity by puf Proteins revealed by crystal structures of yeast puf4p
Nature Structural & Molecular Biology, 2008Co-Authors: Matthew T Miller, Joshua J Higgin, Traci Tanaka M HallAbstract:Pumilio/FBF (PUF) family Proteins are found in eukaryotic organisms and regulate gene expression post-transcriptionally by binding to sequences in the 3′ untranslated region of target transcripts. PUF Proteins contain an RNA binding domain that typically comprises eight α-helical Repeats, each of which recognizes one RNA base. Some PUF Proteins, including yeast Puf4p, have altered RNA binding specificity and use their eight Repeats to bind to RNA sequences with nine or ten bases. Here we report the crystal structures of Puf4p alone and in complex with a 9-nucleotide (nt) target RNA sequence, revealing that Puf4p accommodates an 'extra' nucleotide by modest adaptations allowing one base to be turned away from the RNA binding surface. Using structural information and sequence comparisons, we created a mutant Puf4p Protein that preferentially binds to an 8-nt target RNA sequence over a 9-nt sequence and restores binding of each Protein Repeat to one RNA base.
