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19 results on '"Kocken, Clemens"'

1. The Novel bis-1,2,4-Triazine MIPS-0004373 Demonstrates Rapid and Potent Activity against All Blood Stages of the Malaria Parasite

Author

Ellis, Katherine M., primary, Lucantoni, Leonardo, additional, Chavchich, Marina, additional, Abraham, Matthew, additional, De Paoli, Amanda, additional, Luth, Madeline R., additional, Zeeman, Anne-Marie, additional, Delves, Michael J., additional, Terán, Fernando Sánchez-Román, additional, Straschil, Ursula, additional, Baum, Jake, additional, Kocken, Clemens H. M., additional, Ralph, Stuart A., additional, Winzeler, Elizabeth A., additional, Avery, Vicky M., additional, Edstein, Michael D., additional, Baell, Jonathan B., additional, and Creek, Darren J., additional

Published
2021
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2. PI4 Kinase Is a Prophylactic but Not Radical Curative Target in Plasmodium vivax-Type Malaria Parasites

Author

Zeeman, Anne-Marie, primary, Lakshminarayana, Suresh B., additional, van der Werff, Nicole, additional, Klooster, Els J., additional, Voorberg-van der Wel, Annemarie, additional, Kondreddi, Ravinder R., additional, Bodenreider, Christophe, additional, Simon, Oliver, additional, Sauerwein, Robert, additional, Yeung, Bryan K. S., additional, Diagana, Thierry T., additional, and Kocken, Clemens H. M., additional

Published
2016
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3. KAI407, a Potent Non-8-Aminoquinoline Compound That Kills Plasmodium cynomolgi Early Dormant Liver Stage ParasitesIn Vitro

Author

Zeeman, Anne-Marie, primary, van Amsterdam, Sandra M., additional, McNamara, Case W., additional, Voorberg-van der Wel, Annemarie, additional, Klooster, Els J., additional, van den Berg, Alexander, additional, Remarque, Edmond J., additional, Plouffe, David M., additional, van Gemert, Geert-Jan, additional, Luty, Adrian, additional, Sauerwein, Robert, additional, Gagaring, Kerstin, additional, Borboa, Rachel, additional, Chen, Zhong, additional, Kuhen, Kelli, additional, Glynne, Richard J., additional, Chatterjee, Arnab K., additional, Nagle, Advait, additional, Roland, Jason, additional, Winzeler, Elizabeth A., additional, Leroy, Didier, additional, Campo, Brice, additional, Diagana, Thierry T., additional, Yeung, Bryan K. S., additional, Thomas, Alan W., additional, and Kocken, Clemens H. M., additional

Published
2014
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4. High-Level Expression of Plasmodium vivax Apical Membrane Antigen 1 (AMA-1) in Pichia pastoris: Strong Immunogenicity in Macaca mulatta Immunized with P. vivax AMA-1 and Adjuvant SBAS2

Author

Kocken, Clemens H. M., Dubbeld, Martin A., Van Der Wel, Annemarie, Pronk, Jack T., Waters, Andrew P., Langermans, Jan A. M., and Thomas, Alan W.

Subjects
Vaccines, Synthetic, Protein Conformation, Genetic Vectors, Molecular Sequence Data, Immunization, Secondary, Protozoan Proteins, Antibodies, Protozoan, Membrane Proteins, Antigens, Protozoan, Macaca mulatta, Pichia, Adjuvants, Immunologic, parasitic diseases, Malaria Vaccines, Malaria, Vivax, Mutagenesis, Site-Directed, Animals, Fungal and Parasitic Infections, Plasmodium vivax, Plasmodium cynomolgi
Abstract

The apical membrane antigen 1 (AMA-1) family is a promising family of malaria blood-stage vaccine candidates that have induced protection in rodent and nonhuman primate models of malaria. Correct conformation of the protein appears to be essential for the induction of parasite-inhibitory responses, and these responses appear to be primarily antibody mediated. Here we describe for the first time high-level secreted expression (over 50 mg/liter) of the Plasmodium vivax AMA-1 (PV66/AMA-1) ectodomain by using the methylotrophic yeast Pichia pastoris. To prevent nonnative glycosylation, a conservatively mutagenized PV66/AMA-1 gene (PV66Deltaglyc) lacking N-glycosylation sites was also developed. Expression of the PV66Deltaglyc ectodomain yielded similar levels of a homogeneous product that was nonglycosylated and was readily purified by ion-exchange and gel filtration chromatographies. Recombinant PV66Deltaglyc43-487 was reactive with conformation-dependent monoclonal antibodies. With the SBAS2 adjuvant, Pichia-expressed PV66Deltaglyc43-487 was highly immunogenic in five rhesus monkeys, inducing immunoglobulin G enzyme-linked immunosorbent assay titers in excess of 1:200,000. This group of monkeys had a weak trend showing lower cumulative parasite loads following a Plasmodium cynomolgi infection than in the control group.

Published
1999

5. Diversity Covering AMA1-MSP1 19 Fusion Proteins as Malaria Vaccines

Author

Faber, Bart W., primary, Younis, Sumera, additional, Remarque, Edmond J., additional, Rodriguez Garcia, Roberto, additional, Riasat, Vanessa, additional, Walraven, Vanessa, additional, van der Werff, Nicole, additional, van der Eijk, Marjolein, additional, Cavanagh, David R., additional, Holder, Anthony A., additional, Thomas, Alan W., additional, and Kocken, Clemens H. M., additional

Published
2013
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12. High-Level Expression of the Malaria Blood-Stage Vaccine Candidate Plasmodium falciparum Apical Membrane Antigen 1 and Induction of Antibodies That Inhibit Erythrocyte Invasion

Author

Kocken, Clemens H. M., primary, Withers-Martinez, Chrislaine, additional, Dubbeld, Martin A., additional, Wel, Annemarie van der, additional, Hackett, Fiona, additional, Valderrama, Augusto, additional, Blackman, Michael J., additional, and Thomas, Alan W., additional

Published
2002
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18. KAI407, a potent non-8-aminoquinoline compound that kills Plasmodium cynomolgi early dormant liver stage parasites in vitro.

Author

Zeeman AM, van Amsterdam SM, McNamara CW, Voorberg-van der Wel A, Klooster EJ, van den Berg A, Remarque EJ, Plouffe DM, van Gemert GJ, Luty A, Sauerwein R, Gagaring K, Borboa R, Chen Z, Kuhen K, Glynne RJ, Chatterjee AK, Nagle A, Roland J, Winzeler EA, Leroy D, Campo B, Diagana TT, Yeung BK, Thomas AW, and Kocken CH

Subjects
Animals, Antimalarials therapeutic use, Drug Evaluation, Preclinical methods, Female, Hepatocytes parasitology, Imidazoles therapeutic use, In Vitro Techniques, Liver parasitology, Macaca mulatta parasitology, Malaria parasitology, Malaria prevention & control, Mice, Mice, Inbred ICR, Pyrazines therapeutic use, Sporozoites drug effects, Antimalarials pharmacology, Imidazoles pharmacology, Malaria drug therapy, Plasmodium cynomolgi drug effects, Pyrazines pharmacology
Abstract

Preventing relapses of Plasmodium vivax malaria through a radical cure depends on use of the 8-aminoquinoline primaquine, which is associated with safety and compliance issues. For future malaria eradication strategies, new, safer radical curative compounds that efficiently kill dormant liver stages (hypnozoites) will be essential. A new compound with potential radical cure activity was identified using a low-throughput assay of in vitro-cultured hypnozoite forms of Plasmodium cynomolgi (an excellent and accessible model for Plasmodium vivax). In this assay, primary rhesus hepatocytes are infected with P. cynomolgi sporozoites, and exoerythrocytic development is monitored in the presence of compounds. Liver stage cultures are fixed after 6 days and stained with anti-Hsp70 antibodies, and the relative proportions of small (hypnozoite) and large (schizont) forms relative to the untreated controls are determined. This assay was used to screen a series of 18 known antimalarials and 14 new non-8-aminoquinolines (preselected for blood and/or liver stage activity) in three-point 10-fold dilutions (0.1, 1, and 10 μM final concentrations). A novel compound, designated KAI407 showed an activity profile similar to that of primaquine (PQ), efficiently killing the earliest stages of the parasites that become either primary hepatic schizonts or hypnozoites (50% inhibitory concentration [IC50] for hypnozoites, KAI407, 0.69 μM, and PQ, 0.84 μM; for developing liver stages, KAI407, 0.64 μM, and PQ, 0.37 μM). When given as causal prophylaxis, a single oral dose of 100 mg/kg of body weight prevented blood stage parasitemia in mice. From these results, we conclude that KAI407 may represent a new compound class for P. vivax malaria prophylaxis and potentially a radical cure.

Published
2014
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19. Diversity covering AMA1-MSP119 fusion proteins as malaria vaccines.

Author

Faber BW, Younis S, Remarque EJ, Rodriguez Garcia R, Riasat V, Walraven V, van der Werff N, van der Eijk M, Cavanagh DR, Holder AA, Thomas AW, and Kocken CH

Subjects
Animals, Antibodies, Protozoan blood, Disease Models, Animal, Plasmodium falciparum growth & development, Rabbits, Antigens, Protozoan immunology, Malaria Vaccines immunology, Membrane Proteins immunology, Merozoite Surface Protein 1 immunology, Plasmodium falciparum immunology, Protozoan Proteins immunology
Abstract

To overcome polymorphism in the malaria vaccine candidate Plasmodium falciparum apical membrane antigen 1 (PfAMA1), fusion protein chimeras comprised of three diversity-covering (DiCo) PfAMA1 molecules (D1, D2, and D3) and two allelic variants of the C-terminal 19-kDa region of merozoite surface protein 1 (MSP119) (variants M1 and M2) were generated. A mixture of fusion proteins (D1M1/D2M2D3) and the D1M1D2M2D3 fusion were compared to a single-unit mixture (D1/D2/D3/M1) in an immunological study in groups of rabbits. Following immunization, titers of antibodies (Abs) against four naturally occurring PfAMA1 alleles were high for all groups, as were growth inhibition assay (GIA) levels against two antigenically distinct laboratory parasite strains. Fusion of AMA1 to MSP119 did not suppress levels of antibodies against the AMA1 component. In addition, the breadth of antibody responses was unaffected. Anti-AMA1 antibodies were largely responsible for parasite growth inhibition, as shown in reversal-of-inhibition experiments by adding competing AMA1 antigen. For all groups, titration of the MSP119 antigen into the GIA led to only a small decrease in parasite inhibition, although titers of antibodies against MSP119 were increased 15-fold for the groups immunized with fusion proteins. GIA with affinity-purified anti-MSP119 antibodies showed that the 50% inhibitory concentrations of the anti-MSP119 antibody preparations were in the same order of magnitude for all animals tested, leading to the conclusion that fusing MSP119 to PfAMA1 leads to a small but significant increase in functional antibody levels. This study shows that combination of multiple vaccine candidates in fusion proteins may lead to improved characteristics of the vaccine.

Published
2013
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