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2. Quantification of sporozoite expelling by Anopheles mosquitoes infected with laboratory and naturally circulating P. falciparum gametocytes

Author

Andolina, Chiara, primary, Graumans, Wouter, primary, Guelbeogo, Moussa, additional, van Gemert, Geert-Jan, additional, Ramijth, Jordache, additional, Harouna, Soré, additional, Soumanaba, Zongo, additional, Stoter, Rianne, additional, Vegte-Bolmer, Marga, additional, Pangos, Martina, additional, Sinnis, Photini, additional, Collins, Katharine, additional, Staedke, Sarah G, additional, Tiono, Alfred B, additional, Drakeley, Chris, additional, Lanke, Kjerstin, additional, and Bousema, Teun, additional

Published
2024
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6. A transmission bottleneck for malaria? Quantification of sporozoite expelling from laboratory and natural P. falciparum infections

Author

Andolina, Chiara, primary, Graumans, Wouter, additional, Guelbeogo, Moussa, additional, van Gemert, Geert Jan, additional, Ramjith, Jordache, additional, Harouna, Soré, additional, Soumanaba, Zongo, additional, Stoter, Rianne, additional, Vegte-Bolmer, Marga, additional, Pangos, Martina, additional, Sinnis, Photini, additional, Collins, Katharine, additional, Staedke, Sarah G, additional, Tiono, Alfred B, additional, Drakeley, Chris, additional, Lanke, Kjerstin, additional, and Bousema, Teun, additional

Published
2023
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9. Outcomes of controlled human malaria infection after BCG vaccination

Author

Walk, Jona, de Bree, L. Charlotte J., Graumans, Wouter, Stoter, Rianne, van Gemert, Geert-Jan, van de Vegte-Bolmer, Marga, Teelen, Karina, Hermsen, Cornelus C., Arts, Rob J. W., Behet, Marije C., Keramati, Farid, Moorlag, Simone J. C. F. M., Yang, Annie S. P., van Crevel, Reinout, Aaby, Peter, de Mast, Quirijn, van der Ven, André J. A. M., Stabell Benn, Christine, Netea, Mihai G., and Sauerwein, Robert W.

Published
2019
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10. Pfs230 Domain 7 is targeted by a potent malaria transmissionblocking monoclonal antibody.

Author

Inklaar, Maartje R., de Jong, Roos M., Bekkering, Ezra T., Hikaru Nagaoka, Fennemann, Felix L., Teelen, Karina, van de Vegte-Bolmer, Marga, van Gemert, Geert-Jan, Stoter, Rianne, King, C. Richter, Proellochs, Nicholas I., Bousema, Teun, Eizo Takashima, Takafumi Tsuboi, and Jore, Matthijs M.

Subjects
MONOCLONAL antibodies, ANOPHELES stephensi, OVUM, MALARIA, MALARIA vaccines
Abstract

Malaria transmission-blocking vaccines (TBVs) aim to induce antibodies that block Plasmodium parasite development in the mosquito midgut, thus preventing mosquitoes from becoming infectious. While the Pro-domain and first of fourteen 6-Cysteine domains (Pro-D1) of the Plasmodium gamete surface protein Pfs230 are known targets of transmission-blocking antibodies, no studies to date have discovered other Pfs230 domains that are functional targets. Here, we show that a murine monoclonal antibody (mAb), 18F25.1, targets Pfs230 Domain 7. We generated a subclass-switched complement-fixing variant, mAb 18F25.2a, using a CRISPR/Cas9-based hybridoma engineering method. This subclass-switched mAb 18F25.2a induced lysis of female gametes in vitro. Importantly, mAb 18F25.2a potently reduced P. falciparum infection of Anopheles stephensi mosquitoes in a complementdependent manner, as assessed by standard membrane feeding assays. Together, our data identify Pfs230 Domain 7 as target for transmission-blocking antibodies and provide a strong incentive to study domains outside Pfs230Pro-D1 as TBV candidates. [ABSTRACT FROM AUTHOR]

Published
2023
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11. Protection against malaria after immunization by chloroquine prophylaxis and sporozoites is mediated by preerythrocytic immunity

Author

Bijker, Else M., Bastiaens, Guido J. H., Teirlinck, Anne C., van Gemert, Geert-Jan, Graumans, Wouter, van de Vegte-Bolmer, Marga, Siebelink-Stoter, Rianne, Arens, Theo, Teelen, Karina, Nahrendorf, Wiebke, Remarque, Edmond J., Roeffen, Will, Jansens, Annemieke, Zimmerman, Dunja, Vos, Martijn, van Schaijk, Ben C. L., Wiersma, Jorien, van der Ven, André J. A. M., de Mast, Quirijn, van Lieshout, Lisette, Verweij, Jaco J., Hermsen, Cornelus C., Scholzen, Anja, and Sauerwein, Robert W.

Published
2013

12. NF135.C10: A New Plasmodium falciparum Clone for Controlled Human Malaria Infections

Author

Teirlinck, Anne C., Roestenberg, Meta, van de Vegte-Bolmer, Marga, Scholzen, Anja, Heinrichs, Moniek J. L., Siebelink-Stoter, Rianne, Graumans, Wouter, van Gemert, Geert-Jan, Teelen, Karina, Vos, Martijn W., Nganou-Makamdop, Krystelle, Borrmann, Steffen, Rozier, Yolanda P. A., Erkens, Marianne A. A., Luty, Adrian J. F., Hermsen, Cornelus C., Sim, B. Kim Lee, van Lieshout, Lisette, Hoffman, Stephen L., Visser, Leo G., and Sauerwein, Robert W.

Published
2013
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16. The Complement System Contributes to Functional Antibody-Mediated Responses Induced by Immunization with Plasmodium falciparum Malaria Sporozoites

Author

Behet, Marije C., Kurtovic, Liriye, van Gemert, Geert-Jan, Haukes, Celine M., Siebelink-Stoter, Rianne, Graumans, Wouter, van de Vegte-Bolmer, Marga G., Scholzen, Anja, Langereis, Jeroen D., Diavatopoulos, Dimitri A., Beeson, James G., and Sauerwein, Robert W.

Subjects
sporozoites, IgG, liver stage, Plasmodium falciparum, Vaccination, chemoprophylaxis, immunization, Antimalarials, Microbial Immunity and Vaccines, Antibody Formation, Malaria Vaccines, controlled human malaria infection, antibodies, Humans, complement, Spotlight, Malaria, Falciparum
Abstract

Long-lasting and sterile homologous protection against malaria can be achieved by the exposure of malaria-naive volunteers under chemoprophylaxis to Plasmodium falciparum-infected mosquitoes (chemoprophylaxis and sporozoite [CPS] immunization). While CPS-induced antibodies neutralize sporozoite infectivity in vitro and in vivo, antibody-mediated effector mechanisms are still poorly understood. Here, we investigated whether complement contributes to CPS-induced preerythrocytic immunity. Sera collected before and after CPS immunization in the presence of active or inactive complement were assessed for the recognition of homologous NF54 and heterologous NF135.C10 sporozoites, complement fixation, sporozoite lysis, and possible subsequent effects on in vitro sporozoite infectivity in human hepatocytes. CPS immunization induced sporozoite-specific IgM (P < 0.0001) and IgG (P = 0.001) antibodies with complement-fixing capacities (P < 0.0001). Sporozoite lysis (P = 0.017), traversal (P < 0.0001), and hepatocyte invasion inhibition (P < 0.0001) by CPS-induced antibodies were strongly enhanced in the presence of active complement. Complement-mediated invasion inhibition in the presence of CPS-induced antibodies negatively correlated with cumulative parasitemia during CPS immunizations (P = 0.013). While IgG antibodies similarly recognized homologous and heterologous sporozoites, IgM binding to heterologous sporozoites was reduced (P = 0.023). Although CPS-induced antibodies did not differ in their abilities to fix complement, lyse sporozoites, or inhibit the traversal of homologous and heterologous sporozoites, heterologous sporozoite invasion was more strongly inhibited in the presence of active complement (P = 0.008). These findings demonstrate that CPS-induced antibodies have complement-fixing activity, thereby significantly further enhancing the functional inhibition of homologous and heterologous sporozoite infectivity in vitro. The combined data highlight the importance of complement as an additional immune effector mechanism in preerythrocytic immunity after whole-parasite immunization against Plasmodium falciparum malaria.

Published
2018

17. Pfs230 and Pfs48/45 Fusion Proteins Elicit Strong Transmission-Blocking Antibody Responses Against Plasmodium falciparum

Author

Singh, Susheel K., primary, Thrane, Susan, additional, Chourasia, Bishwanath K., additional, Teelen, Karina, additional, Graumans, Wouter, additional, Stoter, Rianne, additional, van Gemert, Geert-Jan, additional, van de Vegte-Bolmer, Marga G., additional, Nielsen, Morten A., additional, Salanti, Ali, additional, Sander, Adam F., additional, Sauerwein, Robert W., additional, Jore, Matthijs M., additional, and Theisen, Michael, additional

Published
2019
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18. AT-101, a small molecule inhibitor of anti-apoptotic Bcl-2 family members, activates the SAPK/JNK pathway and enhances radiation-induced apoptosis

Author

Rooswinkel Rogier, Bartelink Harry, van Blitterswijk Wim J, Lippman Marc E, Yang Dajun, Kuipers Gitta, Stoter Rianne, Zerp Shuraila F, Lafleur Vincent, and Verheij Marcel

Subjects
Medical physics. Medical radiology. Nuclear medicine, R895-920, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Abstract Background Gossypol, a naturally occurring polyphenolic compound has been identified as a small molecule inhibitor of anti-apoptotic Bcl-2 family proteins. It induces apoptosis in a wide range of tumor cell lines and enhances chemotherapy- and radiation-induced cytotoxicity both in vitro and in vivo. Bcl-2 and related proteins are important inhibitors of apoptosis and frequently overexpressed in human tumors. Increased levels of these proteins confer radio- and chemoresistance and may be associated with poor prognosis. Consequently, inhibition of the anti-apoptotic functions of Bcl-2 family members represents a promising strategy to overcome resistance to anticancer therapies. Methods We tested the effect of (-)-gossypol, also denominated as AT-101, radiation and the combination of both on apoptosis induction in human leukemic cells, Jurkat T and U937. Because activation of the SAPK/JNK pathway is important for apoptosis induction by many different stress stimuli, and Bcl-XL is known to inhibit activation of SAPK/JNK, we also investigated the role of this signaling cascade in AT-101-induced apoptosis using a pharmacologic and genetic approach. Results AT-101 induced apoptosis in a time- and dose-dependent fashion, with ED50 values of 1.9 and 2.4 μM in Jurkat T and U937 cells, respectively. Isobolographic analysis revealed a synergistic interaction between AT-101 and radiation, which also appeared to be sequence-dependent. Like radiation, AT-101 activated SAPK/JNK which was blocked by the kinase inhibitor SP600125. In cells overexpressing a dominant-negative mutant of c-Jun, AT-101-induced apoptosis was significantly reduced. Conclusion Our data show that AT-101 strongly enhances radiation-induced apoptosis in human leukemic cells and indicate a requirement for the SAPK/JNK pathway in AT-101-induced apoptosis. This type of apoptosis modulation may overcome treatment resistance and lead to the development of new effective combination therapies.

Published
2009
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19. Pfs230 and Pfs48/45 fusion proteins elicit strong transmission-blocking antibody responses against Plasmodium falciparum

Author

Singh, Susheel K, Thrane, Susan, Chourasia, Bishwanath K, Teelen, Karina, Graumans, Wouter, Stoter, Rianne, van Gemert, Geert-Jan, van de Vegte-Bolmer, Marga G, Nielsen, Morten A, Salanti, Ali, Sander, Adam F, Sauerwein, Robert W, Jore, Matthijs M, Theisen, Michael, Singh, Susheel K, Thrane, Susan, Chourasia, Bishwanath K, Teelen, Karina, Graumans, Wouter, Stoter, Rianne, van Gemert, Geert-Jan, van de Vegte-Bolmer, Marga G, Nielsen, Morten A, Salanti, Ali, Sander, Adam F, Sauerwein, Robert W, Jore, Matthijs M, and Theisen, Michael

Abstract

The Plasmodium falciparum Pfs230 and Pfs48/45 proteins are expressed during transmission from man to mosquito and are leading candidates for a malaria transmission blocking vaccine. Individually they generate transmission blocking (TB) antibodies in rodent models. Whether the single protein vaccines are suitable to use in field settings will primarily depend on their potency to elicit functional antibodies. We hypothesized that a combination of both proteins will be more potent than each protein individually. Therefore we designed chimeric proteins composed of fragments of both Pfs230 and Pfs48/45 as well as single protein fragments, and expressed these in Lactoccus lactis. Both the individual Pfs230 and Pfs48/45 fragments and chimeras elicited high levels of functional antibodies in mice. Importantly, one of the chimeric proteins elicited over threefold higher transmission blocking antibody responses than the single antigens alone. Furthermore the immunogenicity of one of the chimeras could be enhanced through coupling to a virus-like particle (VLP). Altogether these data support further clinical development of these novel constructs.

Published
2019

20. Predicting the likelihood and intensity of mosquito infection from sex specific Plasmodium falciparum gametocyte density

Author

Bradley, John, primary, Stone, Will, additional, Da, Dari F, additional, Morlais, Isabelle, additional, Dicko, Alassane, additional, Cohuet, Anna, additional, Guelbeogo, Wamdaogo M, additional, Mahamar, Almahamoudou, additional, Nsango, Sandrine, additional, Soumaré, Harouna M, additional, Diawara, Halimatou, additional, Lanke, Kjerstin, additional, Graumans, Wouter, additional, Siebelink-Stoter, Rianne, additional, van de Vegte-Bolmer, Marga, additional, Chen, Ingrid, additional, Tiono, Alfred, additional, Gonçalves, Bronner Pamplona, additional, Gosling, Roland, additional, Sauerwein, Robert W, additional, Drakeley, Chris, additional, Churcher, Thomas S, additional, and Bousema, Teun, additional

Published
2018
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21. Author response: Predicting the likelihood and intensity of mosquito infection from sex specific Plasmodium falciparum gametocyte density

Author

Bradley, John, primary, Stone, Will, additional, Da, Dari F, additional, Morlais, Isabelle, additional, Dicko, Alassane, additional, Cohuet, Anna, additional, Guelbeogo, Wamdaogo M, additional, Mahamar, Almahamoudou, additional, Nsango, Sandrine, additional, Soumaré, Harouna M, additional, Diawara, Halimatou, additional, Lanke, Kjerstin, additional, Graumans, Wouter, additional, Siebelink-Stoter, Rianne, additional, van de Vegte-Bolmer, Marga, additional, Chen, Ingrid, additional, Tiono, Alfred, additional, Gonçalves, Bronner Pamplona, additional, Gosling, Roland, additional, Sauerwein, Robert W, additional, Drakeley, Chris, additional, Churcher, Thomas S, additional, and Bousema, Teun, additional

Published
2018
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22. Publisher Correction: Unravelling the immune signature of Plasmodium falciparum transmission-reducing immunity

Author

Stone, Will J. R., primary, Campo, Joseph J., additional, Ouédraogo, André Lin, additional, Meerstein-Kessel, Lisette, additional, Morlais, Isabelle, additional, Da, Dari, additional, Cohuet, Anna, additional, Nsango, Sandrine, additional, Sutherland, Colin J., additional, van de Vegte-Bolmer, Marga, additional, Siebelink-Stoter, Rianne, additional, van Gemert, Geert-Jan, additional, Graumans, Wouter, additional, Lanke, Kjerstin, additional, Shandling, Adam D., additional, Pablo, Jozelyn V., additional, Teng, Andy A., additional, Jones, Sophie, additional, de Jong, Roos M., additional, Fabra-García, Amanda, additional, Bradley, John, additional, Roeffen, Will, additional, Lasonder, Edwin, additional, Gremo, Giuliana, additional, Schwarzer, Evelin, additional, Janse, Chris J., additional, Singh, Susheel K., additional, Theisen, Michael, additional, Felgner, Phil, additional, Marti, Matthias, additional, Drakeley, Chris, additional, Sauerwein, Robert, additional, Bousema, Teun, additional, and Jore, Matthijs M., additional

Published
2018
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23. Probabilistic data integration identifies reliable gametocyte-specific proteins and transcripts in malaria parasites

Author

Meerstein-Kessel, Lisette, van der Lee, Robin, Stone, Will, Lanke, Kjerstin H.W., Baker, David A, Alano, Pietro, Silvestrini, Francesco, Janse, Chris J, Khan, Shahid M, van de Vegte-Bolmer, Marga, Graumans, Wouter, Siebelink-Stoter, Rianne, Kooij, Taco W A, Marti, Matthias, Drakeley, Chris, Campo, Joseph J, van Dam, Teunis J P, Sauerwein, Robert, Bousema, Teun, Huynen, Martijn A, Meerstein-Kessel, Lisette, van der Lee, Robin, Stone, Will, Lanke, Kjerstin H.W., Baker, David A, Alano, Pietro, Silvestrini, Francesco, Janse, Chris J, Khan, Shahid M, van de Vegte-Bolmer, Marga, Graumans, Wouter, Siebelink-Stoter, Rianne, Kooij, Taco W A, Marti, Matthias, Drakeley, Chris, Campo, Joseph J, van Dam, Teunis J P, Sauerwein, Robert, Bousema, Teun, and Huynen, Martijn A

Abstract

Plasmodium gametocytes are the sexual forms of the malaria parasite essential for transmission to mosquitoes. To better understand how gametocytes differ from asexual blood-stage parasites, we performed a systematic analysis of available 'omics data for P. falciparum and other Plasmodium species. 18 transcriptomic and proteomic data sets were evaluated for the presence of curated "gold standards" of 41 gametocyte-specific versus 46 non-gametocyte genes and integrated using Bayesian probabilities, resulting in gametocyte-specificity scores for all P. falciparum genes. To illustrate the utility of the gametocyte score, we explored newly predicted gametocyte-specific genes as potential biomarkers of gametocyte carriage and exposure. We analyzed the humoral immune response in field samples against 30 novel gametocyte-specific antigens and found five antigens to be differentially recognized by gametocyte carriers as compared to malaria-infected individuals without detectable gametocytes. We also validated the gametocyte-specificity of 15 identified gametocyte transcripts on culture material and samples from naturally infected individuals, resulting in eight transcripts that were >1000-fold higher expressed in gametocytes compared to asexual parasites and whose transcript abundance allowed gametocyte detection in naturally infected individuals. Our integrated genome-wide gametocyte-specificity scores provide a comprehensive resource to identify targets and monitor P. falciparum gametocytemia.

Published
2018

24. Probabilistic data integration identifies reliable gametocyte-specific proteins and transcripts in malaria parasites

Author

Sub Bioinformatics, Meerstein-Kessel, Lisette, van der Lee, Robin, Stone, Will, Lanke, Kjerstin H.W., Baker, David A, Alano, Pietro, Silvestrini, Francesco, Janse, Chris J, Khan, Shahid M, van de Vegte-Bolmer, Marga, Graumans, Wouter, Siebelink-Stoter, Rianne, Kooij, Taco W A, Marti, Matthias, Drakeley, Chris, Campo, Joseph J, van Dam, Teunis J P, Sauerwein, Robert, Bousema, Teun, Huynen, Martijn A, Sub Bioinformatics, Meerstein-Kessel, Lisette, van der Lee, Robin, Stone, Will, Lanke, Kjerstin H.W., Baker, David A, Alano, Pietro, Silvestrini, Francesco, Janse, Chris J, Khan, Shahid M, van de Vegte-Bolmer, Marga, Graumans, Wouter, Siebelink-Stoter, Rianne, Kooij, Taco W A, Marti, Matthias, Drakeley, Chris, Campo, Joseph J, van Dam, Teunis J P, Sauerwein, Robert, Bousema, Teun, and Huynen, Martijn A

Published
2018

25. Unravelling the immune signature of Plasmodium falciparum transmission-reducing immunity

Author

Stone, Will J R, Campo, Joseph J, Ouédraogo, André Lin, Meerstein-Kessel, Lisette, Morlais, Isabelle, Da, Dari, Cohuet, Anna, Nsango, Sandrine, Sutherland, Colin J, van de Vegte-Bolmer, Marga, Siebelink-Stoter, Rianne, van Gemert, Geert-Jan, Graumans, Wouter, Lanke, Kjerstin, Shandling, Adam D, Pablo, Jozelyn V, Teng, Andy A, Jones, Sophie, de Jong, Roos M, Fabra-García, Amanda, Bradley, John, Roeffen, Will, Lasonder, Edwin, Gremo, Giuliana, Schwarzer, Evelin, Janse, Chris J, Singh, Susheel K, Theisen, Michael, Felgner, Phil, Marti, Matthias, Drakeley, Chris, Sauerwein, Robert, Bousema, Teun, Jore, Matthijs M, Stone, Will J R, Campo, Joseph J, Ouédraogo, André Lin, Meerstein-Kessel, Lisette, Morlais, Isabelle, Da, Dari, Cohuet, Anna, Nsango, Sandrine, Sutherland, Colin J, van de Vegte-Bolmer, Marga, Siebelink-Stoter, Rianne, van Gemert, Geert-Jan, Graumans, Wouter, Lanke, Kjerstin, Shandling, Adam D, Pablo, Jozelyn V, Teng, Andy A, Jones, Sophie, de Jong, Roos M, Fabra-García, Amanda, Bradley, John, Roeffen, Will, Lasonder, Edwin, Gremo, Giuliana, Schwarzer, Evelin, Janse, Chris J, Singh, Susheel K, Theisen, Michael, Felgner, Phil, Marti, Matthias, Drakeley, Chris, Sauerwein, Robert, Bousema, Teun, and Jore, Matthijs M

Abstract

Infection with Plasmodium can elicit antibodies that inhibit parasite survival in the mosquito, when they are ingested in an infectious blood meal. Here, we determine the transmission-reducing activity (TRA) of naturally acquired antibodies from 648 malaria-exposed individuals using lab-based mosquito-feeding assays. Transmission inhibition is significantly associated with antibody responses to Pfs48/45, Pfs230, and to 43 novel gametocyte proteins assessed by protein microarray. In field-based mosquito-feeding assays the likelihood and rate of mosquito infection are significantly lower for individuals reactive to Pfs48/45, Pfs230 or to combinations of the novel TRA-associated proteins. We also show that naturally acquired purified antibodies against key transmission-blocking epitopes of Pfs48/45 and Pfs230 are mechanistically involved in TRA, whereas sera depleted of these antibodies retain high-level, complement-independent TRA. Our analysis demonstrates that host antibody responses to gametocyte proteins are associated with reduced malaria transmission efficiency from humans to mosquitoes.

Published
2018

26. A randomized feasibility trial comparing four antimalarial drug regimens to induce Plasmodium falciparum gametocytemia in the controlled human malaria infection model

Author

Reuling, Isaie J, primary, van de Schans, Lisanne A, additional, Coffeng, Luc E, additional, Lanke, Kjerstin, additional, Meerstein-Kessel, Lisette, additional, Graumans, Wouter, additional, van Gemert, Geert-Jan, additional, Teelen, Karina, additional, Siebelink-Stoter, Rianne, additional, van de Vegte-Bolmer, Marga, additional, de Mast, Quirijn, additional, van der Ven, André J, additional, Ivinson, Karen, additional, Hermsen, Cornelus C, additional, de Vlas, Sake, additional, Bradley, John, additional, Collins, Katharine A, additional, Ockenhouse, Christian F, additional, McCarthy, James, additional, Sauerwein, Robert W, additional, and Bousema, Teun, additional

Published
2018
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27. Unravelling the immune signature of Plasmodium falciparum transmission-reducing immunity

Author

Stone, Will J. R., primary, Campo, Joseph J., additional, Ouédraogo, André Lin, additional, Meerstein-Kessel, Lisette, additional, Morlais, Isabelle, additional, Da, Dari, additional, Cohuet, Anna, additional, Nsango, Sandrine, additional, Sutherland, Colin J., additional, van de Vegte-Bolmer, Marga, additional, Siebelink-Stoter, Rianne, additional, van Gemert, Geert-Jan, additional, Graumans, Wouter, additional, Lanke, Kjerstin, additional, Shandling, Adam D., additional, Pablo, Jozelyn V., additional, Teng, Andy A., additional, Jones, Sophie, additional, de Jong, Roos M., additional, Fabra-García, Amanda, additional, Bradley, John, additional, Roeffen, Will, additional, Lasonder, Edwin, additional, Gremo, Giuliana, additional, Schwarzer, Evelin, additional, Janse, Chris J., additional, Singh, Susheel K., additional, Theisen, Michael, additional, Felgner, Phil, additional, Marti, Matthias, additional, Drakeley, Chris, additional, Sauerwein, Robert, additional, Bousema, Teun, additional, and Jore, Matthijs M., additional

Published
2018
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28. Probabilistic data integration identifies reliable gametocyte-specific proteins and transcripts in malaria parasites

Author

Meerstein-Kessel, Lisette, primary, van der Lee, Robin, additional, Stone, Will, additional, Lanke, Kjerstin, additional, Baker, David A., additional, Alano, Pietro, additional, Silvestrini, Francesco, additional, Janse, Chris J., additional, Khan, Shahid M., additional, van de Vegte-Bolmer, Marga, additional, Graumans, Wouter, additional, Siebelink-Stoter, Rianne, additional, Kooij, Taco W. A., additional, Marti, Matthias, additional, Drakeley, Chris, additional, Campo, Joseph J., additional, van Dam, Teunis J. P., additional, Sauerwein, Robert, additional, Bousema, Teun, additional, and Huynen, Martijn A., additional

Published
2018
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29. Author response: A randomized feasibility trial comparing four antimalarial drug regimens to induce Plasmodium falciparum gametocytemia in the controlled human malaria infection model

Author

Reuling, Isaie J, primary, van de Schans, Lisanne A, additional, Coffeng, Luc E, additional, Lanke, Kjerstin, additional, Meerstein-Kessel, Lisette, additional, Graumans, Wouter, additional, van Gemert, Geert-Jan, additional, Teelen, Karina, additional, Siebelink-Stoter, Rianne, additional, van de Vegte-Bolmer, Marga, additional, de Mast, Quirijn, additional, van der Ven, André J, additional, Ivinson, Karen, additional, Hermsen, Cornelus C, additional, de Vlas, Sake, additional, Bradley, John, additional, Collins, Katharine A, additional, Ockenhouse, Christian F, additional, McCarthy, James, additional, Sauerwein, Robert W, additional, and Bousema, Teun, additional

Published
2017
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30. Comparative assessment of An. gambiae and An. stephensi mosquitoes to determine transmission-reducing activity of antibodies against P. falciparum sexual stage antigens

Author

Eldering, Maarten, primary, Bompard, Anaïs, additional, Miura, Kazutoyo, additional, Stone, Will, additional, Morlais, Isabelle, additional, Cohuet, Anna, additional, van Gemert, Geert-Jan, additional, Brock, Patrick M., additional, Rijpma, Sanna R., additional, van de Vegte-Bolmer, Marga, additional, Graumans, Wouter, additional, Siebelink-Stoter, Rianne, additional, Da, Dari F., additional, Long, Carole A., additional, Morin, Merribeth J., additional, Sauerwein, Robert W., additional, Churcher, Thomas S., additional, and Bousema, Teun, additional

Published
2017
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31. Probabilistic data integration identifies reliable gametocyte-specific proteins and transcripts in malaria parasites

Author

Meerstein-Kessel, Lisette, primary, van der Lee, Robin, additional, Stone, Will, additional, Lanke, Kjerstin, additional, Baker, David A, additional, Alano, Pietro, additional, Silvestrini, Francesco, additional, Janse, Chris J, additional, Khan, Shahid M, additional, van de Vegte-Bolmer, Marga, additional, Graumans, Wouter, additional, Siebelink-Stoter, Rianne, additional, Kooij, Taco WA, additional, Marti, Matthias, additional, Drakeley, Chris, additional, Campo, Joseph J., additional, van Dam, Teunis JP, additional, Sauerwein, Robert, additional, Bousema, Teun, additional, and Huynen, Martijn A, additional

Published
2017
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32. Modest heterologous protection after Plasmodium falciparum sporozoite immunization: a double-blind randomized controlled clinical trial

Author

Walk, Jona, primary, Reuling, Isaie J., additional, Behet, Marije C., additional, Meerstein-Kessel, Lisette, additional, Graumans, Wouter, additional, van Gemert, Geert-Jan, additional, Siebelink-Stoter, Rianne, additional, van de Vegte-Bolmer, Marga, additional, Janssen, Thorsten, additional, Teelen, Karina, additional, de Wilt, Johannes H. W., additional, de Mast, Quirijn, additional, van der Ven, André J., additional, Diez Benavente, Ernest, additional, Campino, Susana, additional, Clark, Taane G., additional, Huynen, Martijn A., additional, Hermsen, Cornelus C., additional, Bijker, Else M., additional, Scholzen, Anja, additional, and Sauerwein, Robert W., additional

Published
2017
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33. Semi-high-throughput detection of Plasmodium falciparum and Plasmodium vivax oocysts in mosquitoes using bead-beating followed by circumsporozoite ELISA and quantitative PCR

Author

Graumans, Wouter, primary, Tadesse, Fitsum G., additional, Andolina, Chiara, additional, van Gemert, Geert-Jan, additional, Teelen, Karina, additional, Lanke, Kjerstin, additional, Gadisa, Endalamaw, additional, Yewhalaw, Delenasaw, additional, van de Vegte-Bolmer, Marga, additional, Siebelink-Stoter, Rianne, additional, Reuling, Isaïe, additional, Sauerwein, Robert, additional, and Bousema, Teun, additional

Published
2017
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34. Concentration of Plasmodium falciparum gametocytes in whole blood samples by magnetic cell sorting enhances parasite infection rates in mosquito feeding assays

Author

Reuling, Isaie J., primary, Stone, Will J. R., additional, van de Vegte-Bolmer, Marga, additional, van Gemert, Geert-Jan, additional, Siebelink-Stoter, Rianne, additional, Graumans, Wouter, additional, Lanke, Kjerstin, additional, Bousema, Teun, additional, and Sauerwein, Robert W., additional

Published
2017
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35. Pf s230 and Pf s48/45 Fusion Proteins Elicit Strong Transmission-Blocking Antibody Responses Against Plasmodium falciparum.

Author

Singh, Susheel K., Thrane, Susan, Chourasia, Bishwanath K., Teelen, Karina, Graumans, Wouter, Stoter, Rianne, van Gemert, Geert-Jan, van de Vegte-Bolmer, Marga G., Nielsen, Morten A., Salanti, Ali, Sander, Adam F., Sauerwein, Robert W., Jore, Matthijs M., and Theisen, Michael

Subjects
CHIMERIC proteins, ANTIBODY formation, PLASMODIUM falciparum, VIRUS-like particles, PROTEIN engineering
Abstract

The Plasmodium falciparum Pf s230 and Pf s48/45 proteins are expressed during transmission from man to mosquito and are leading candidates for a malaria transmission blocking vaccine. Individually they generate transmission blocking (TB) antibodies in rodent models. Whether the single protein vaccines are suitable to use in field settings will primarily depend on their potency to elicit functional antibodies. We hypothesized that a combination of both proteins will be more potent than each protein individually. Therefore we designed chimeric proteins composed of fragments of both Pf s230 and Pf s48/45 as well as single protein fragments, and expressed these in Lactoccus lactis. Both the individual Pf s230 and Pf s48/45 fragments and chimeras elicited high levels of functional antibodies in mice. Importantly, one of the chimeric proteins elicited over threefold higher transmission blocking antibody responses than the single antigens alone. Furthermore the immunogenicity of one of the chimeras could be enhanced through coupling to a virus-like particle (VLP). Altogether these data support further clinical development of these novel constructs. [ABSTRACT FROM AUTHOR]

Published
2019
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36. Vital and dispensable roles ofPlasmodiummultidrug resistance transporters during blood- and mosquito-stage development

Author

Rijpma, Sanna R., primary, van der Velden, Maarten, additional, Annoura, Takeshi, additional, Matz, Joachim M., additional, Kenthirapalan, Sanketha, additional, Kooij, Taco W. A., additional, Matuschewski, Kai, additional, van Gemert, Geert-Jan, additional, van de Vegte-Bolmer, Marga, additional, Siebelink-Stoter, Rianne, additional, Graumans, Wouter, additional, Ramesar, Jai, additional, Klop, Onny, additional, Russel, Frans G. M., additional, Sauerwein, Robert W., additional, Janse, Chris J., additional, Franke-Fayard, Blandine M., additional, and Koenderink, Jan B., additional

Published
2016
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37. Variation in susceptibility of African Plasmodium falciparum malaria parasites to TEP1 mediated killing in Anopheles gambiae mosquitoes

Author

Eldering, Maarten, primary, Morlais, Isabelle, additional, van Gemert, Geert-Jan, additional, van de Vegte-Bolmer, Marga, additional, Graumans, Wouter, additional, Siebelink-Stoter, Rianne, additional, Vos, Martijn, additional, Abate, Luc, additional, Roeffen, Will, additional, Bousema, Teun, additional, Levashina, Elena A., additional, and Sauerwein, Robert W., additional

Published
2016
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38. The relevance and applicability of oocyst prevalence as a read-out for mosquito feeding assays

Author

Stone, Will J. R., primary, Eldering, Maarten, additional, van Gemert, Geert-Jan, additional, Lanke, Kjerstin H. W., additional, Grignard, Lynn, additional, van de Vegte-Bolmer, Marga G., additional, Siebelink-Stoter, Rianne, additional, Graumans, Wouter, additional, Roeffen, Will F. G., additional, Drakeley, Chris J., additional, Sauerwein, Robert W., additional, and Bousema, Teun, additional

Published
2013
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39. Vital and dispensable roles of Plasmodium multidrug resistance transporters during blood- and mosquito-stage development.

Author

Rijpma, Sanna R., van der Velden, Maarten, Annoura, Takeshi, Matz, Joachim M., Kenthirapalan, Sanketha, Kooij, Taco W. A., Matuschewski, Kai, van Gemert, Geert‐Jan, van de Vegte‐Bolmer, Marga, Siebelink‐Stoter, Rianne, Graumans, Wouter, Ramesar, Jai, Klop, Onny, Russel, Frans G. M., Sauerwein, Robert W., Janse, Chris J., Franke‐Fayard, Blandine M., and Koenderink, Jan B.

Subjects
PLASMODIUM, DRUG resistance, MULTIDRUG resistance-associated proteins, ATP-binding cassette transporters, ANTIMALARIALS
Abstract

Multidrug resistance (MDR) proteins belong to the B subfamily of the ATP Binding Cassette (ABC) transporters, which export a wide range of compounds including pharmaceuticals. In this study, we used reverse genetics to study the role of all seven Plasmodium MDR proteins during the life cycle of malaria parasites. Four P. berghei genes (encoding MDR1, 4, 6 and 7) were refractory to deletion, indicating a vital role during blood stage multiplication and validating them as potential targets for antimalarial drugs. Mutants lacking expression of MDR2, MDR3 and MDR5 were generated in both P. berghei and P. falciparum, indicating a dispensable role for blood stage development. Whereas P. berghei mutants lacking MDR3 and MDR5 had a reduced blood stage multiplication in vivo, blood stage growth of P. falciparum mutants in vitro was not significantly different. Oocyst maturation and sporozoite formation in Plasmodium mutants lacking MDR2 or MDR5 was reduced. Sporozoites of these P. berghei mutants were capable of infecting mice and life cycle completion, indicating the absence of vital roles during liver stage development. Our results demonstrate vital and dispensable roles of MDR proteins during blood stages and an important function in sporogony for MDR2 and MDR5 in both Plasmodium species. [ABSTRACT FROM AUTHOR]

Published
2016
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40. NF135.C10: A New Plasmodium falciparum Clone for Controlled Human Malaria Infections

Author

Teirlinck, Anne C., primary, Roestenberg, Meta, additional, van de Vegte-Bolmer, Marga, additional, Scholzen, Anja, additional, Heinrichs, Moniek J. L., additional, Siebelink-Stoter, Rianne, additional, Graumans, Wouter, additional, van Gemert, Geert-Jan, additional, Teelen, Karina, additional, Vos, Martijn W., additional, Nganou-Makamdop, Krystelle, additional, Borrmann, Steffen, additional, Rozier, Yolanda P. A., additional, Erkens, Marianne A. A., additional, Luty, Adrian J. F., additional, Hermsen, Cornelus C., additional, Sim, B. Kim Lee, additional, van Lieshout, Lisette, additional, Hoffman, Stephen L., additional, Visser, Leo G., additional, and Sauerwein, Robert W., additional

Published
2012
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42. Publisher Correction: Unravelling the immune signature of Plasmodium falciparum transmission-reducing immunity

Author

Stone, Will J. R., Campo, Joseph J., Ouédraogo, André Lin, Meerstein-Kessel, Lisette, Morlais, Isabelle, Da, Dari, Cohuet, Anna, Nsango, Sandrine, Sutherland, Colin J., van de Vegte-Bolmer, Marga, Siebelink-Stoter, Rianne, van Gemert, Geert-Jan, Graumans, Wouter, Lanke, Kjerstin, Shandling, Adam D., Pablo, Jozelyn V., Teng, Andy A., Jones, Sophie, de Jong, Roos M., Fabra-García, Amanda, Bradley, John, Roeffen, Will, Lasonder, Edwin, Gremo, Giuliana, Schwarzer, Evelin, Janse, Chris J., Singh, Susheel K., Theisen, Michael, Felgner, Phil, Drakeley, Chris, Sauerwein, Robert, Bousema, Teun, Jore, Matthijs M., and Marti, Matthias

Abstract

Version of Record

Published
2018
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43. Unravelling the immune signature of Plasmodium falciparum transmission-reducing immunity

Author

Stone, Will J. R., Campo, Joseph J., Ouédraogo, André Lin, Meerstein-Kessel, Lisette, Morlais, Isabelle, Da, Dari, Cohuet, Anna, Nsango, Sandrine, Sutherland, Colin J., van de Vegte-Bolmer, Marga, Siebelink-Stoter, Rianne, van Gemert, Geert-Jan, Graumans, Wouter, Lanke, Kjerstin, Shandling, Adam D., Pablo, Jozelyn V., Teng, Andy A., Jones, Sophie, de Jong, Roos M., Fabra-García, Amanda, Bradley, John, Roeffen, Will, Lasonder, Edwin, Gremo, Giuliana, Schwarzer, Evelin, Janse, Chris J., Singh, Susheel K., Theisen, Michael, Felgner, Phil, Drakeley, Chris, Sauerwein, Robert, Bousema, Teun, Jore, Matthijs M., and Marti, Matthias

Abstract

Infection with Plasmodium can elicit antibodies that inhibit parasite survival in the mosquito, when they are ingested in an infectious blood meal. Here, we determine the transmission-reducing activity (TRA) of naturally acquired antibodies from 648 malaria-exposed individuals using lab-based mosquito-feeding assays. Transmission inhibition is significantly associated with antibody responses to Pfs48/45, Pfs230, and to 43 novel gametocyte proteins assessed by protein microarray. In field-based mosquito-feeding assays the likelihood and rate of mosquito infection are significantly lower for individuals reactive to Pfs48/45, Pfs230 or to combinations of the novel TRA-associated proteins. We also show that naturally acquired purified antibodies against key transmission-blocking epitopes of Pfs48/45 and Pfs230 are mechanistically involved in TRA, whereas sera depleted of these antibodies retain high-level, complement-independent TRA. Our analysis demonstrates that host antibody responses to gametocyte proteins are associated with reduced malaria transmission efficiency from humans to mosquitoes., Version of Record

Published
2018
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44. MOESM1 of Concentration of Plasmodium falciparum gametocytes in whole blood samples by magnetic cell sorting enhances parasite infection rates in mosquito feeding assays

Author

Isaie Reuling, Stone, Will, Vegte-Bolmer, Marga De, Geert-Jan Gemert, Siebelink-Stoter, Rianne, Graumans, Wouter, Lanke, Kjerstin, Bousema, Teun, and Sauerwein, Robert

Subjects
3. Good health
Abstract

Additional file 1: Figure S1. Association between gametocyte densities and oocystâ prevalence and density. A. Overview of gametocyte densities and infection rates of experiments of Figs. 1, 2, 3, 4 and Additional file 2: Figure S2. B. Overview of gametocyte densities and mean oocysts of experiments of Figs. 1, 2, 3, 4 and Additional file 2: Figure S2.

45. Additional file 1: of Modest heterologous protection after Plasmodium falciparum sporozoite immunization: a double-blind randomized controlled clinical trial

Author

Walk, Jona, Isaie Reuling, Behet, Marije, Meerstein-Kessel, Lisette, Graumans, Wouter, Geert-Jan Van Gemert, Siebelink-Stoter, Rianne, Vegte-Bolmer, Marga Van De, Janssen, Thorsten, Teelen, Karina, Wilt, Johannes De, Mast, Quirijn De, AndrĂŠ Van Der Ven, Benavente, Ernest Diez, Campino, Susana, Taane Clark, Huynen, Martijn, Cornelus Hermsen, Bijker, Else, Scholzen, Anja, and Sauerwein, Robert

Subjects
3. Good health
Abstract

Protocol. Malaria antigen-specific IgG ELISA (S1). Isolation and cultivation of primary human hepatocytes (S2). In vitro sporozoite infectivity assay of primary human hepatocytes (S3). Immunofluorescent analysis of P. falciparum-infected primary human hepatocytes (S4). In vitro PBMC restimulation with PfRBCs and flow cytometry staining (S5) [11, 12, 14, 17, 42]. (DOCX 20 kb)

46. MOESM1 of Semi-high-throughput detection of Plasmodium falciparum and Plasmodium vivax oocysts in mosquitoes using bead-beating followed by circumsporozoite ELISA and quantitative PCR

Author

Graumans, Wouter, Fitsum Tadesse, Andolina, Chiara, Geert-Jan Gemert, Teelen, Karina, Lanke, Kjerstin, Endalamaw Gadisa, Delenasaw Yewhalaw, Vegte-Bolmer, Marga De, Siebelink-Stoter, Rianne, IsaĂŻe Reuling, Sauerwein, Robert, and Bousema, Teun

Subjects
parasitic diseases, 3. Good health
Abstract

Additional file 1: Table S1. Observations with different buffers for mosquito homogenisation. Table S2. Experimental infection data CT values by qPCR vs Optical Density in CSP-ELISA. Table S3. Overview of processing time of the four methods compared in seconds per 80 mosquitoes. Figure S1. Protocol for mixed infection detection using the same 50Â Âľl volume. Homogenate is transferred from the prior experiments to the subsequent ones. It is important that every step is timed and thought ahead on when to start the different steps. Figure S2. Processing of mosquitoes by CS-ELISA when tested for both P. falciparum and P. vivax.

47. Additional file 1: of Modest heterologous protection after Plasmodium falciparum sporozoite immunization: a double-blind randomized controlled clinical trial

Author

Walk, Jona, Isaie Reuling, Behet, Marije, Meerstein-Kessel, Lisette, Graumans, Wouter, Geert-Jan Van Gemert, Siebelink-Stoter, Rianne, Vegte-Bolmer, Marga Van De, Janssen, Thorsten, Teelen, Karina, Wilt, Johannes De, Mast, Quirijn De, AndrĂŠ Van Der Ven, Benavente, Ernest Diez, Campino, Susana, Taane Clark, Huynen, Martijn, Cornelus Hermsen, Bijker, Else, Scholzen, Anja, and Sauerwein, Robert

Subjects
3. Good health
Abstract

Protocol. Malaria antigen-specific IgG ELISA (S1). Isolation and cultivation of primary human hepatocytes (S2). In vitro sporozoite infectivity assay of primary human hepatocytes (S3). Immunofluorescent analysis of P. falciparum-infected primary human hepatocytes (S4). In vitro PBMC restimulation with PfRBCs and flow cytometry staining (S5) [11, 12, 14, 17, 42]. (DOCX 20 kb)

48. Additional file 2 of A portfolio of geographically distinct laboratory-adapted Plasmodium falciparum clones with consistent infection rates in Anopheles mosquitoes

Author

van de Vegte-Bolmer, Marga, Graumans, Wouter, Stoter, Rianne, van Gemert, Geert-Jan, Sauerwein, Robert, Collins, Katharine A., and Bousema, Teun

Subjects
3. Good health
Abstract

Additional file 2: Table S1. Geographical origin and country last visited of collected isolates. Table S2. Transmission results of patient isolates and derived clones to mosquito vector.

49. Additional file 2: Figure S1. of Modest heterologous protection after Plasmodium falciparum sporozoite immunization: a double-blind randomized controlled clinical trial

Author

Walk, Jona, Isaie Reuling, Behet, Marije, Meerstein-Kessel, Lisette, Graumans, Wouter, Geert-Jan Van Gemert, Siebelink-Stoter, Rianne, Vegte-Bolmer, Marga Van De, Janssen, Thorsten, Teelen, Karina, Wilt, Johannes De, Mast, Quirijn De, Ven, André Van Der, Benavente, Ernest Diez, Campino, Susana, Taane Clark, Huynen, Martijn, Cornelus Hermsen, Bijker, Else, Scholzen, Anja, and Sauerwein, Robert

Subjects
13. Climate action, parasitic diseases, 3. Good health
Abstract

First-wave parasitemia after challenge. Parasitemia on day 7 post-challenge in immunized (open circles) and control (closed circles) volunteers. The line and error bars show the geometric mean and 95% CI interval. Figure S2. Inhibition of in vitro homologous and heterologous intra-hepatic sporozoite development in primary human hepatocytes by mAb 2A10. P. falciparum NF54 (blue), NF135.C10 (orange) and NF166.C8 (green) sporozoites in the presence of 10% heat-inactivated naive human control serum were pre-incubated with 3-fold serial dilutions of the 2A10 monoclonal antibody (0.027–20 μg/mL), targeting the repeat region of the circumsporozoite protein (CSP), and added to primary human hepatocyte cultures. Six days post-infection, the number of P. falciparum-infected hepatocytes was assessed as described in Additional file 1: S4 and S5. Figure S3. Amino acid changes in CSP. Table S1. Whole-genome sequencing statistics. Table S2. Mosquito salivary gland infectivity and sporozoite load of the three clones. Mean mosquito salivary gland infectivity and sporozoite load determined 1 day prior to challenge infection by dissecting a sample of 10 mosquitoes per strain. (DOCX 427 kb)

50. MOESM2 of Concentration of Plasmodium falciparum gametocytes in whole blood samples by magnetic cell sorting enhances parasite infection rates in mosquito feeding assays

Author

Isaie Reuling, Stone, Will, Vegte-Bolmer, Marga De, Geert-Jan Gemert, Siebelink-Stoter, Rianne, Graumans, Wouter, Lanke, Kjerstin, Bousema, Teun, and Sauerwein, Robert

Subjects
3. Good health
Abstract

Additional file 2: Figure S2. Effect of different flow-rate MACS on gametocyte infectivity. Number of oocysts per mosquito after membrane-feeding assay (MIDI cages). 1 600 µL of gametocyte-infected whole blood from starting material, fed directly. 2 9000 µL of gametocyte-infected whole blood from starting material added once over MACS column with 23G needle, eluted and reconstituted in 600 µL of uninfected blood before feed. 3 9000 µL of gametocyte-infected whole blood from starting material added once over MACS column with 21G needle, eluted and reconstituted in 600 µL of uninfected blood before feed. Vertical bars indicate mean with SEM.

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