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51. Proteome-wide analysis of a malaria vaccine study reveals personalized humoral immune profiles in Tanzanian adults

Author

Camponovo, Flavia, primary, Campo, Joseph J, additional, Le, Timothy Q, additional, Oberai, Amit, additional, Hung, Christopher, additional, Pablo, Jozelyn V, additional, Teng, Andy A, additional, Liang, Xiaowu, additional, Sim, B Kim Lee, additional, Jongo, Said, additional, Abdulla, Salim, additional, Tanner, Marcel, additional, Hoffman, Stephen L, additional, Daubenberger, Claudia, additional, and Penny, Melissa A, additional

Published
2020
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52. Author response: Proteome-wide analysis of a malaria vaccine study reveals personalized humoral immune profiles in Tanzanian adults

Author

Camponovo, Flavia, primary, Campo, Joseph J, additional, Le, Timothy Q, additional, Oberai, Amit, additional, Hung, Christopher, additional, Pablo, Jozelyn V, additional, Teng, Andy A, additional, Liang, Xiaowu, additional, Sim, B Kim Lee, additional, Jongo, Said, additional, Abdulla, Salim, additional, Tanner, Marcel, additional, Hoffman, Stephen L, additional, Daubenberger, Claudia, additional, and Penny, Melissa A, additional

Published
2020
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53. Antigen-stimulated PBMC transcriptional protective signatures for malaria immunization

Author

Moncunill, Gemma, primary, Scholzen, Anja, additional, Mpina, Maximillian, additional, Nhabomba, Augusto, additional, Hounkpatin, Aurore Bouyoukou, additional, Osaba, Lourdes, additional, Valls, Raquel, additional, Campo, Joseph J., additional, Sanz, Hèctor, additional, Jairoce, Chenjerai, additional, Williams, Nana Aba, additional, Pasini, Erica M., additional, Arteta, David, additional, Maynou, Joan, additional, Palacios, Lourdes, additional, Duran-Frigola, Miquel, additional, Aponte, John J., additional, Kocken, Clemens H. M., additional, Agnandji, Selidji Todagbe, additional, Mas, José Manuel, additional, Mordmüller, Benjamin, additional, Daubenberger, Claudia, additional, Sauerwein, Robert, additional, and Dobaño, Carlota, additional

Published
2020
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54. Immune system development varies according to age, location, and anemia in African children

Author

Hill, Danika L., primary, Carr, Edward J., additional, Rutishauser, Tobias, additional, Moncunill, Gemma, additional, Campo, Joseph J., additional, Innocentin, Silvia, additional, Mpina, Maxmillian, additional, Nhabomba, Augusto, additional, Tumbo, Anneth, additional, Jairoce, Chenjerai, additional, Moll, Henriëtte A., additional, van Zelm, Menno C., additional, Dobaño, Carlota, additional, Daubenberger, Claudia, additional, and Linterman, Michelle A., additional

Published
2020
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56. Antibody Biomarkers Associated with Sterile Protection Induced by Controlled Human Malaria Infection under Chloroquine Prophylaxis

Author

Obiero, J.M., Campo, Joseph J., Scholzen, A., Randall, Arlo, Bijker, E.M., Roestenberg, M., Hermsen, C.C., Sauerwein, R.W., Felgner, Philip L., Obiero, J.M., Campo, Joseph J., Scholzen, A., Randall, Arlo, Bijker, E.M., Roestenberg, M., Hermsen, C.C., Sauerwein, R.W., and Felgner, Philip L.

Abstract

Contains fulltext : 201910.pdf (publisher's version ) (Open Access)

Published
2019

57. Panproteome-wide analysis of antibody responses to whole cell pneumococcal vaccination

Author

Campo, Joseph J, Le, Timothy Q, Pablo, Jozelyn V, Hung, Christopher, Teng, Andy A, Tettelin, Hervé, Tate, Andrea, Hanage, William P, Alderson, Mark R, Liang, Xiaowu, Malley, Richard, Lipsitch, Marc, Croucher, Nicholas J, and Wellcome Trust

Subjects
Life Sciences & Biomedicine - Other Topics, Time Factors, Proteome, STREPTOCOCCUS-PNEUMONIAE, PROTEIN, Aluminum Hydroxide, PSPA, COLONIZATION, Placebos, Pneumococcal Vaccines, immunology, Immunology and Inflammation, antibody, vaccine, Longitudinal Studies, PROTECTION, Biology (General), Microbiology and Infectious Disease, Antibodies, Bacterial, Healthy Volunteers, REPLACEMENT, Medicine, INACTIVATION, Life Sciences & Biomedicine, Research Article, Adult, Drug-Related Side Effects and Adverse Reactions, QH301-705.5, Science, infectious disease, protein antigen, Protein Array Analysis, IMMUNITY, panproteome array, Young Adult, Adjuvants, Immunologic, Humans, INTRANASAL IMMUNIZATION, human, Biology, antigenic diversity, Science & Technology, microbiology, S. pneumoniae, Vaccines, Inactivated, inflammation, Immunoglobulin G, Antibody Formation, Other, CROSS-REACTIVE ANTIBODIES
Abstract

Pneumococcal whole cell vaccines (WCVs) could cost-effectively protect against a greater strain diversity than current capsule-based vaccines. Immunoglobulin G (IgG) responses to a WCV were characterised by applying longitudinally-sampled sera, available from 35 adult placebo-controlled phase I trial participants, to a panproteome microarray. Despite individuals maintaining distinctive antibody ‘fingerprints’, responses were consistent across vaccinated cohorts. Seventy-two functionally distinct proteins were associated with WCV-induced increases in IgG binding. These shared characteristics with naturally immunogenic proteins, being enriched for transporters and cell wall metabolism enzymes, likely unusually exposed on the unencapsulated WCV’s surface. Vaccine-induced responses were specific to variants of the diverse PclA, PspC and ZmpB proteins, whereas PspA- and ZmpA-induced antibodies recognised a broader set of alleles. Temporal variation in IgG levels suggested a mixture of anamnestic and novel responses. These reproducible increases in IgG binding to a limited, but functionally diverse, set of conserved proteins indicate WCV could provide species-wide immunity. Clinical trial registration: The trial was registered with ClinicalTrials.gov with Identifier NCT01537185; the results are available from https://clinicaltrials.gov/ct2/show/results/NCT01537185., eLife digest Streptococcus pneumoniae is a bug that causes pneumonia and meningitis, killing around a million people each year. Vaccines now exist to protect young children against these diseases, but they are expensive and do not work against all the strains of the bacteria. This is because these shots train the body’s immune system to recognize and attack the bacterium’s capsule, a layer of sugars that surrounds the microbe and is often different between strains. One possible solution could be a cheap, whole cell vaccine. These injections expose the body to genetically modified S. pneumoniae that do not carry the capsule. Such treatment has now been tested in a small number of people during a clinical trial. Here, Campo et al. use a technique known as panproteome array to scan samples collected during this trial, and identify which elements the body learns to recognize when it is exposed to the genetically manipulated strain of S. pneumoniae. The results show that when volunteers receive this vaccine, their body targets proteins that the capsule normally shields from the immune system. Many of these proteins are very similar across all strains of S. pneumoniae, which means that the whole cell vaccine could potentially better protect against a broad spectrum of bacteria. However, further studies are needed to assess whether this is the case, especially in infants.

Published
2018

58. Corrigendum: Chronic Exposure to Malaria Is Associated with Inhibitory and Activation Markers on Atypical Memory B Cells and Marginal Zone-Like B Cells

Author

Ubillos, Itziar, primary, Campo, Joseph J., additional, Requena, Pilar, additional, Ome-Kaius, Maria, additional, Hanieh, Sarah, additional, Rose, Honor, additional, Samol, Paula, additional, Barrios, Diana, additional, Jiménez, Alfons, additional, Bardají, Azucena, additional, Mueller, Ivo, additional, Menéndez, Clara, additional, Rogerson, Stephen, additional, Moncunill, Gemma, additional, and Dobaño, Carlota, additional

Published
2019
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59. Naturally acquired immunity against immaturePlasmodium falciparumgametocytes

Author

Dantzler, Kathleen W., primary, Ma, Siyuan, additional, Ngotho, Priscilla, additional, Stone, Will J. R., additional, Tao, Dingyin, additional, Rijpma, Sanna, additional, De Niz, Mariana, additional, Nilsson Bark, Sandra K., additional, Jore, Matthijs M., additional, Raaijmakers, Tonke K., additional, Early, Angela M., additional, Ubaida-Mohien, Ceereena, additional, Lemgruber, Leandro, additional, Campo, Joseph J., additional, Teng, Andy A., additional, Le, Timothy Q., additional, Walker, Cassidy L., additional, Hermand, Patricia, additional, Deterre, Philippe, additional, Davies, D. Huw, additional, Felgner, Phil, additional, Morlais, Isabelle, additional, Wirth, Dyann F., additional, Neafsey, Daniel E., additional, Dinglasan, Rhoel R., additional, Laufer, Miriam, additional, Huttenhower, Curtis, additional, Seydel, Karl, additional, Taylor, Terrie, additional, Bousema, Teun, additional, and Marti, Matthias, additional

Published
2019
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60. Differential Patterns of IgG Subclass Responses to Plasmodium falciparum Antigens in Relation to Malaria Protection and RTS,S Vaccination

Author

Dobaño, Carlota, primary, Santano, Rebeca, additional, Vidal, Marta, additional, Jiménez, Alfons, additional, Jairoce, Chenjerai, additional, Ubillos, Itziar, additional, Dosoo, David, additional, Aguilar, Ruth, additional, Williams, Nana Aba, additional, Díez-Padrisa, Núria, additional, Ayestaran, Aintzane, additional, Valim, Clarissa, additional, Asante, Kwaku Poku, additional, Owusu-Agyei, Seth, additional, Lanar, David, additional, Chauhan, Virander, additional, Chitnis, Chetan, additional, Dutta, Sheetij, additional, Angov, Evelina, additional, Gamain, Benoit, additional, Coppel, Ross L., additional, Beeson, James G., additional, Reiling, Linda, additional, Gaur, Deepak, additional, Cavanagh, David, additional, Gyan, Ben, additional, Nhabomba, Augusto J., additional, Campo, Joseph J., additional, and Moncunill, Gemma, additional

Published
2019
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61. 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

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

Author

Stone, W.J.R., Campo, Joseph J., Ouedraogo, A.L., Meerstein-Kessel, L., Morlais, I., Da, D.F., Vegte-Bolmer, M.G. van de, Siebelink-Stoter, R., Gemert, G.J.A. van, Graumans, W., Lanke, K.H., Jong, R.M. de, Roeffen, W., Sauerwein, R.W., Bousema, T., Jore, M.M., Stone, W.J.R., Campo, Joseph J., Ouedraogo, A.L., Meerstein-Kessel, L., Morlais, I., Da, D.F., Vegte-Bolmer, M.G. van de, Siebelink-Stoter, R., Gemert, G.J.A. van, Graumans, W., Lanke, K.H., Jong, R.M. de, Roeffen, W., Sauerwein, R.W., Bousema, T., and Jore, M.M.

Abstract

Contains fulltext : 184080.pdf (publisher's version ) (Open Access)

Published
2018

63. 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

64. 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

65. Panproteome-wide analysis of antibody responses to whole cell pneumococcal vaccination

Author

Campo, Joseph J, primary, Le, Timothy Q, additional, Pablo, Jozelyn V, additional, Hung, Christopher, additional, Teng, Andy A, additional, Tettelin, Hervé, additional, Tate, Andrea, additional, Hanage, William P, additional, Alderson, Mark R, additional, Liang, Xiaowu, additional, Malley, Richard, additional, Lipsitch, Marc, additional, and Croucher, Nicholas J, additional

Published
2018
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66. Author response: Panproteome-wide analysis of antibody responses to whole cell pneumococcal vaccination

Author

Campo, Joseph J, primary, Le, Timothy Q, additional, Pablo, Jozelyn V, additional, Hung, Christopher, additional, Teng, Andy A, additional, Tettelin, Hervé, additional, Tate, Andrea, additional, Hanage, William P, additional, Alderson, Mark R, additional, Liang, Xiaowu, additional, Malley, Richard, additional, Lipsitch, Marc, additional, and Croucher, Nicholas J, additional

Published
2018
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67. Analysis of factors affecting the variability of a quantitative suspension bead array assay measuring IgG to multiple Plasmodium antigens

Author

Ubillos, Itziar, primary, Aguilar, Ruth, additional, Sanz, Hector, additional, Jiménez, Alfons, additional, Vidal, Marta, additional, Valmaseda, Aida, additional, Dong, Yan, additional, Gaur, Deepak, additional, Chitnis, Chetan E., additional, Dutta, Sheetij, additional, Angov, Evelina, additional, Aponte, John J., additional, Campo, Joseph J., additional, Valim, Clarissa, additional, Harezlak, Jaroslaw, additional, and Dobaño, Carlota, additional

Published
2018
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68. 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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69. 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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70. 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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72. Assessment of the Combined Effect of Epstein–Barr Virus and Plasmodium falciparum Infections on Endemic Burkitt Lymphoma Using a Multiplex Serological Approach

Author

Aguilar, Ruth, primary, Casabonne, Delphine, additional, O’Callaghan-Gordo, Cristina, additional, Vidal, Marta, additional, Campo, Joseph J., additional, Mutalima, Nora, additional, Angov, Evelina, additional, Dutta, Sheetij, additional, Gaur, Deepak, additional, Chitnis, Chetan E., additional, Chauhan, Virander, additional, Michel, Angelika, additional, de Sanjosé, Silvia, additional, Waterboer, Tim, additional, Kogevinas, Manolis, additional, Newton, Rob, additional, and Dobaño, Carlota, additional

Published
2017
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73. 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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75. RTS,S/AS01E Malaria Vaccine Induces Memory and Polyfunctional T Cell Responses in a Pediatric African Phase III Trial

Author

Moncunill, Gemma, primary, De Rosa, Stephen C., additional, Ayestaran, Aintzane, additional, Nhabomba, Augusto J., additional, Mpina, Maximillian, additional, Cohen, Kristen W., additional, Jairoce, Chenjerai, additional, Rutishauser, Tobias, additional, Campo, Joseph J., additional, Harezlak, Jaroslaw, additional, Sanz, Héctor, additional, Díez-Padrisa, Núria, additional, Williams, Nana Aba, additional, Morris, Daryl, additional, Aponte, John J., additional, Valim, Clarissa, additional, Daubenberger, Claudia, additional, Dobaño, Carlota, additional, and McElrath, M. Juliana, additional

Published
2017
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76. Chronic Exposure to Malaria Is Associated with Inhibitory and Activation Markers on Atypical Memory B Cells and Marginal Zone-Like B Cells

Author

Ubillos, Itziar, primary, Campo, Joseph J., additional, Requena, Pilar, additional, Ome-Kaius, Maria, additional, Hanieh, Sarah, additional, Rose, Honor, additional, Samol, Paula, additional, Barrios, Diana, additional, Jiménez, Alfons, additional, Bardají, Azucena, additional, Mueller, Ivo, additional, Menéndez, Clara, additional, Rogerson, Stephen, additional, Moncunill, Gemma, additional, and Dobaño, Carlota, additional

Published
2017
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79. Controlled human malaria infection by intramuscular and direct venous inoculation of cryopreserved Plasmodium falciparum sporozoites in malaria-naïve volunteers : effect of injection volume and dose on infectivity rates

Author

Gómez-Pérez, Gloria P, Legarda, Almudena, Muñoz, Jose, Sim, B Kim Lee, Ballester, Maria Rosa, Dobaño, Carlota, Moncunill, Gemma, Campo, Joseph J, Cisteró, Pau, Jimenez, Alfons, Barrios, Diana, Mordmüller, Benjamin, Pardos, Josefina, Navarro, Mireia, Zita, Cecilia Justino, Nhamuave, Carlos Arlindo, García-Basteiro, Alberto L, Sanz, Ariadna, Aldea, Marta, Manoj, Anita, Gunasekera, Anusha, Billingsley, Peter F, Aponte, John J, James, Eric R, Guinovart, Caterina, Antonijoan Arbós, Rosa Ma., Kremsner, Peter G, Hoffman, Stephen L, Alonso, Pedro L, Gómez-Pérez, Gloria P, Legarda, Almudena, Muñoz, Jose, Sim, B Kim Lee, Ballester, Maria Rosa, Dobaño, Carlota, Moncunill, Gemma, Campo, Joseph J, Cisteró, Pau, Jimenez, Alfons, Barrios, Diana, Mordmüller, Benjamin, Pardos, Josefina, Navarro, Mireia, Zita, Cecilia Justino, Nhamuave, Carlos Arlindo, García-Basteiro, Alberto L, Sanz, Ariadna, Aldea, Marta, Manoj, Anita, Gunasekera, Anusha, Billingsley, Peter F, Aponte, John J, James, Eric R, Guinovart, Caterina, Antonijoan Arbós, Rosa Ma., Kremsner, Peter G, Hoffman, Stephen L, and Alonso, Pedro L

Abstract

Controlled human malaria infection (CHMI) by mosquito bite is a powerful tool for evaluation of vaccines and drugs against Plasmodium falciparum malaria. However, only a small number of research centres have the facilities required to perform such studies. CHMI by needle and syringe could help to accelerate the development of anti-malaria interventions by enabling centres worldwide to employ CHMI. An open-label CHMI study was performed with aseptic, purified, cryopreserved P. falciparum sporozoites (PfSPZ Challenge) in 36 malaria naïve volunteers. In part A, the effect of the inoculation volume was assessed: 18 participants were injected intramuscularly (IM) with a dose of 2,500 PfSPZ divided into two injections of 10 µL (n = 6), 50 µL (n = 6) or 250 µL (n = 6), respectively. In part B, the injection volume that resulted in highest infectivity rates in part A (10 µL) was used to formulate IM doses of 25,000 PfSPZ (n = 6) and 75,000 PfSPZ (n = 6) divided into two 10-µL injections. Results from a parallel trial led to the decision to add a positive control group (n = 6), each volunteer receiving 3,200 PfSPZ in a single 500-µL injection by direct venous inoculation (DVI). Four/six participants in the 10-µL group, 1/6 in the 50-µL group and 2/6 in the 250-µL group developed parasitaemia. Geometric mean (GM) pre-patent periods were 13.9, 14.0 and 15.0 days, respectively. Six/six (100%) participants developed parasitaemia in the 25,000 and 75,000 PfSPZ IM and 3,200 PfSPZ DVI groups. GM pre-patent periods were 12.2, 11.4 and 11.4 days, respectively. Injection of PfSPZ Challenge was well tolerated and safe in all groups. IM injection of 75,000 PfSPZ and DVI injection of 3,200 PfSPZ resulted in infection rates and pre-patent periods comparable to the bite of five PfSPZ-infected mosquitoes. Remarkably, it required 23.4-fold more PfSPZ administered IM than DVI to achieve the same parasite kinetics. These results allow for translation of CHMI from research to routine use, and i

Published
2015

80. Controlled human malaria infection by intramuscular and direct venous inoculation of cryopreserved Plasmodium falciparum sporozoites in malaria-naïve volunteers: effect of injection volume and dose on infectivity rates

Author

Gómez-Pérez, Gloria P, primary, Legarda, Almudena, additional, Muñoz, Jose, additional, Sim, B Kim Lee, additional, Ballester, María Rosa, additional, Dobaño, Carlota, additional, Moncunill, Gemma, additional, Campo, Joseph J, additional, Cisteró, Pau, additional, Jimenez, Alfons, additional, Barrios, Diana, additional, Mordmüller, Benjamin, additional, Pardos, Josefina, additional, Navarro, Mireia, additional, Zita, Cecilia Justino, additional, Nhamuave, Carlos Arlindo, additional, García-Basteiro, Alberto L, additional, Sanz, Ariadna, additional, Aldea, Marta, additional, Manoj, Anita, additional, Gunasekera, Anusha, additional, Billingsley, Peter F, additional, Aponte, John J, additional, James, Eric R, additional, Guinovart, Caterina, additional, Antonijoan, Rosa M, additional, Kremsner, Peter G, additional, Hoffman, Stephen L, additional, and Alonso, Pedro L, additional

Published
2015
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81. Pregnancy and Malaria Exposure Are Associated with Changes in the B Cell Pool and in Plasma Eotaxin Levels

Author

Requena, Pilar, primary, Campo, Joseph J., additional, Umbers, Alexandra J., additional, Ome, Maria, additional, Wangnapi, Regina, additional, Barrios, Diana, additional, Robinson, Leanne J., additional, Samol, Paula, additional, Rosanas-Urgell, Anna, additional, Ubillos, Itziar, additional, Mayor, Alfredo, additional, López, Marta, additional, de Lazzari, Elisa, additional, Arévalo-Herrera, Myriam, additional, Fernández-Becerra, Carmen, additional, del Portillo, Hernando, additional, Chitnis, Chetan E., additional, Siba, Peter M., additional, Bardají, Azucena, additional, Mueller, Ivo, additional, Rogerson, Stephen, additional, Menéndez, Clara, additional, and Dobaño, Carlota, additional

Published
2014
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83. High Antibody Responses against Plasmodium falciparum in Immigrants after Extended Periods of Interrupted Exposure to Malaria

Author

Moncunill, Gemma, primary, Mayor, Alfredo, additional, Jiménez, Alfons, additional, Nhabomba, Augusto, additional, Casas-Vila, Núria, additional, Puyol, Laura, additional, Campo, Joseph J., additional, Manaca, Maria Nelia, additional, Aguilar, Ruth, additional, Pinazo, María-Jesús, additional, Almirall, Mercè, additional, Soler, Cristina, additional, Muñoz, José, additional, Bardají, Azucena, additional, Angov, Evelina, additional, Dutta, Sheetij, additional, Chitnis, Chetan E., additional, Alonso, Pedro L., additional, Gascón, Joaquim, additional, and Dobaño, Carlota, additional

Published
2013
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84. 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, Marti, Matthias, Drakeley, Chris, Sauerwein, Robert, Bousema, Teun, and Jore, Matthijs M.

Published
2018
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85. 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, 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
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87. Publisher Correction: Unravelling the immune signature of Plasmodium falciparum transmissionreducing immunity.

Author

Meerstein-Kessel, Lisette, Sauerwein, Robert, Stone, Will J. R., Bousema, Teun, Bradley, John, Lasonder, Edwin, Gremo, Giuliana, Schwarzer, Evelin, Janse, Chris J., Singh, Susheel K., Theisen, Michael, Felgner, Phil, Marti, Matthias, Sutherland, Colin J., Jones, Sophie, Drakeley, Chris, Campo, Joseph J., Shandling, Adam D., Pablo, Jozelyn V., and Teng, Andy A.

Subjects
PLASMODIUM, PLASMODIIDAE, PLASMODIUM berghei, IMMUNITY, AGGLUTINATION
Abstract

A correction of supplementary data to Nature Communication is corrected, which was published in 8th February, 2018 edition.

Published
2018
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88. Impact of the RTS,S Malaria Vaccine Candidate on Naturally Acquired Antibody Responses to Multiple Asexual Blood Stage Antigens

Author

Campo, Joseph J., primary, Dobaño, Carlota, additional, Sacarlal, Jahit, additional, Guinovart, Caterina, additional, Mayor, Alfredo, additional, Angov, Evelina, additional, Dutta, Sheetij, additional, Chitnis, Chetan, additional, Macete, Eusebio, additional, Aponte, John J., additional, and Alonso, Pedro L., additional

Published
2011
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90. Feasibility of Flow Cytometry for Measurements of Plasmodium falciparum Parasite Burden in Studies in Areas of Malaria Endemicity by Use of Bidimensional Assessment of YOYO-1 and Autofluorescence

Author

Campo, Joseph J., primary, Aponte, John J., additional, Nhabomba, Augusto J., additional, Sacarlal, Jahit, additional, Angulo-Barturen, Iñigo, additional, Jiménez-Díaz, María Belén, additional, Alonso, Pedro L., additional, and Dobaño, Carlota, additional

Published
2011
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92. RTS,S/AS01E Malaria Vaccine Induces Memory and Polyfunctional T Cell Responses in a Pediatric African Phase III Trial

Author

Moncunill, Gemma, De Rosa, Stephen C., Ayestaran, Aintzane, Nhabomba, Augusto J., Mpina, Maximillian, Cohen, Kristen W., Jairoce, Chenjerai, Rutishauser, Tobias, Campo, Joseph J., Harezlak, Jaroslaw, Sanz, Héctor, Díez-Padrisa, Núria, Williams, Nana Aba, Morris, Daryl, Aponte, John J., Valim, Clarissa, Daubenberger, Claudia, Dobaño, Carlota, and McElrath, M. Juliana

Subjects
malaria, vaccine, cellular immune responses, T cells, intracellular cytokine staining, flow cytometry
Abstract

Comprehensive assessment of cellular responses to the RTS,S/AS01E vaccine is needed to understand potential correlates and ultimately mechanisms of protection against malaria disease. Cellular responses recognizing the RTS,S/AS01E-containing circumsporozoite protein (CSP) and Hepatitis B surface antigen (HBsAg) were assessed before and 1 month after primary vaccination by intracellular cytokine staining and 16-color flow cytometry in 105 RTS,S/AS01-vaccinated and 74 rabies-vaccinated participants (controls) in a pediatric phase III trial in Africa. RTS,S/AS01E-vaccinated children had significantly higher frequencies of CSP- and HBsAg-specific CD4+ T cells producing IL-2, TNF-α, and CD40L and HBsAg-specific CD4+ T producing IFN-γ and IL-17 than baseline and the control group. Vaccine-induced responses were identified in both central and effector memory (EM) compartments. EM CD4+ T cells expressing IL-4 and IL-21 were detected recognizing both vaccine antigens. Consistently higher response rates to both antigens in RTS,S/AS01E-vaccinated than comparator-vaccinated children were observed. RTS,S/AS01E induced polyfunctional CSP- and HBsAg-specific CD4+ T cells, with a greater degree of polyfunctionality in HBsAg responses. In conclusion, RTS,S/AS01E vaccine induces T cells of higher functional heterogeneity and polyfunctionality than previously characterized. Responses detected in memory CD4+ T cell compartments may provide correlates of RTS,S/AS01-induced immunity and duration of protection in future correlates of immunity studies.

Published
2017
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93. Author Correction: Antibody responses to the RTS,S/AS01E vaccine and Plasmodium falciparum antigens after a booster dose within the phase 3 trial in Mozambique.

Author

Sánchez, Lina, Vidal, Marta, Jairoce, Chenjerai, Aguilar, Ruth, Ubillos, Itziar, Cuamba, Inocencia, Nhabomba, Augusto J., Williams, Nana Aba, Díez-Padrisa, Núria, Cavanagh, David, Angov, Evelina, Coppel, Ross L., Gaur, Deepak, Beeson, James G., Dutta, Sheetij, Aide, Pedro, Campo, Joseph J., Moncunill, Gemma, and Dobaño, Carlota

Subjects
BOOSTER vaccines, VACCINE effectiveness, CLINICAL trials, ANTIBODY formation, PLASMODIUM falciparum, IMMUNOGLOBULINS
Abstract

Correction to: I npj Vaccines i https://doi.org/10.1038/s41541-020-0192-7, published online 04 June 2020 In the original version of this Article, the Data Availability statement was missing the link to the datasets generated during the study. The Data Availability statement has now been updated in both the HTML and PDF versions of the Article. [Extracted from the article]

Published
2022
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94. Feasibility of Flow Cytometry for Measurements of Plasmodium falciparumParasite Burden in Studies in Areas of Malaria Endemicity by Use of Bidimensional Assessment of YOYO-1 and Autofluorescence

Author

Campo, Joseph J., Aponte, John J., Nhabomba, Augusto J., Sacarlal, Jahit, Angulo-Barturen, Iñigo, Jiménez-Díaz, María Belén, Alonso, Pedro L., and Dobaño, Carlota

Abstract

ABSTRACTThe detection and quantification of Plasmodium falciparumin studies of malaria endemicity primarily relies upon microscopy. High-throughput quantitative methods with less subjectivity and greater reliability are needed for investigational studies. The staining of parasitized erythrocytes with YOYO-1 for flow cytometry bears great potential as a tool for assessing malaria parasite burden. Capillary blood was collected from children presenting to the pediatric ward of the Manhiça District Hospital in Mozambique for parasitemia assessment by thick and thin blood films, flow cytometry (YOYO-1530/585), and quantitative real-time PCR (qRT-PCR). Whole blood was fixed and stained with YOYO-1 for acquisition on a cytometer to assess the frequency of infected erythrocyte events. qRT-PCR was used as the gold standard for the detection of P. falciparum. The YOYO-1530/585method was as sensitive and specific as conventional microscopy (area under the receiver operating characteristic, 0.9 for both methods). The interrater mean difference for YOYO-1530/585was near zero. Parasite density using flow cytometry and complete blood counts returned density estimates with a mean difference 2.2 times greater than results by microscopy (confidence interval, 1.46 to 3.60) but with limits of agreement between 10 times lower and 50 times higher than those of microscopy. The YOYO-1530/585staining pattern was established exactly as demonstrated in animal models, but the assay was limited by the lack of appropriate negative-control samples for establishing background levels and the definition of positives in areas in which malaria is endemic. YOYO-1530/585is a high-throughput tool with great potential if the limitations of negative controls and heterogeneous levels of background signal can be overcome.

Published
2011
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95. Naturally acquired immunity against immature Plasmodium falciparum gametocytes.

Author

Dantzler, Kathleen W., Ma, Siyuan, Ngotho, Priscilla, Stone, Will J. R., Tao, Dingyin, Rijpma, Sanna, De Niz, Mariana, Nilsson Bark, Sandra K., Jore, Matthijs M., Raaijmakers, Tonke K., Early, Angela M., Ubaida-Mohien, Ceereena, Lemgruber, Leandro, Campo, Joseph J., Teng, Andy A., Le, Timothy Q., Walker, Cassidy L., Hermand, Patricia, Deterre, Philippe, and Davies, D. Huw

Abstract

Naturally acquired immune responses target infected red blood cell surface antigens of immature malaria transmission stages. Targeting transmission: Effective malaria vaccines to block transmission of Plasmodium falciparum may require targeting of different antigens than those that are currently being studied. To identify candidate antigens, Dantzler et al. studied immune responses from large cohorts of people that had been infected with P. falciparum. They used multiple complementary assays to study how antibodies recognize different stages of gametocytes, the sexual stage that allows transmission from human blood into mosquitoes. Immune sera recognized immature but not mature gametocytes inside red blood cells. They further studied a selection of candidate antigens that are not present in other stages and are relatively conserved across P. falciparum strains. Strong natural immunity to these antigens indicates that a vaccine may be designed to induce protective immune responses that could potentially interfere with transmission. The recent decline in global malaria burden has stimulated efforts toward Plasmodium falciparum elimination. Understanding the biology of malaria transmission stages may provide opportunities to reduce or prevent onward transmission to mosquitoes. Immature P. falciparum transmission stages, termed stages I to IV gametocytes, sequester in human bone marrow before release into the circulation as mature stage V gametocytes. This process likely involves interactions between host receptors and potentially immunogenic adhesins on the infected red blood cell (iRBC) surface. Here, we developed a flow cytometry assay to examine immune recognition of live gametocytes of different developmental stages by naturally exposed Malawians. We identified strong antibody recognition of the earliest immature gametocyte-iRBCs (giRBCs) but not mature stage V giRBCs. Candidate surface antigens (n = 30), most of them shared between asexual- and gametocyte-iRBCs, were identified by mass spectrometry and mouse immunizations, as well as correlations between responses by protein microarray and flow cytometry. Naturally acquired responses to a subset of candidate antigens were associated with reduced asexual and gametocyte density, and plasma samples from malaria-infected individuals were able to induce immune clearance of giRBCs in vitro. Infected RBC surface expression of select candidate antigens was validated using specific antibodies, and genetic analysis revealed a subset with minimal variation across strains. Our data demonstrate that humoral immune responses to immature giRBCs and shared iRBC antigens are naturally acquired after malaria exposure. These humoral immune responses may have consequences for malaria transmission potential by clearing developing gametocytes, which could be leveraged for malaria intervention. [ABSTRACT FROM AUTHOR]

Published
2019
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96. ANTIBODY RESPONSE AFTER CHALLENGE WITH PLASMODIUM FALCIPARUM SPOROZOITES BY NEEDLE AND SYRINGE WITH DIFFERENT DOSES AND ROUTES IN MALARIA-NAIVE AND SEMI-IMMUNE INDIVIDUALS

Author

Gomez-Perez, Gloria P., Mordmueller, Benjamin, Lell, Bertrand, Campo, Joseph J., Vidal, Marta, Valmaseda, Aida, Moncunill, Gemma, Jimenez, Alfons, Cistero, Pau, Barrios, Diana, Mayor, Alfredo, Angov, Evelina, Dutta, Sheetij, Chitnis, Chetan, Chauhan, Virander, Gaur, Deepak, James, Eric, Billingsley, Peter, Sim, Kim Lee, Chakravarty, Sumana, Legarda, Almudena, Hoffman, Stephen L., Kremsner, Peter, Pedro Luis Alonso, and Dobano, Carlota

97. Baseline exposure, antibody subclass, and hepatitis B response differentially affect malaria protective immunity following RTS,S/AS01E vaccination in African children

Author

Ubillos, Itziar, Ayestaran, Aintzane, Nhabomba, Augusto J., Dosoo, David, Vidal, Marta, Jiménez, Alfons, Jairoce, Chenjerai, Sanz, Hèctor, Aguilar, Ruth, Williams, Nana Aba, Díez-Padrisa, Núria, Mpina, Maximilian, Sorgho, Hermann, Agnandji, Selidji Todagbe, Kariuki, Simon, Mordmüller, Benjamin, Daubenberger, Claudia, Asante, Kwaku Poku, Owusu-Agyei, Seth, Sacarlal, Jahit, Aide, Pedro, Aponte, John J., Dutta, Sheetij, Gyan, Ben, Campo, Joseph J., Valim, Clarissa, Moncunill, Gemma, and Dobaño, Carlota

Subjects
3. Good health

98. Concentration and avidity of antibodies to different circumsporozoite epitopes correlate with RTS,S/AS01E malaria vaccine efficacy

Author

Dobaño, Carlota, Sanz, Hèctor, Sorgho, Hermann, Dosoo, David, Mpina, Maximilian, Ubillos, Itziar, Aguilar, Ruth, Ford, Tom, Díez-Padrisa, Núria, Williams, Nana Aba, Ayestaran, Aintzane, Traore, Ousmane, Nhabomba, Augusto J., Jairoce, Chenjerai, Waitumbi, John, Agnandji, Selidji Todagbe, Kariuki, Simon, Abdulla, Salim, Aponte, John J., Mordmüller, Benjamin, Asante, Kwaku Poku, Owusu-Agyei, Seth, Tinto, Halidou, Campo, Joseph J., Moncunill, Gemma, Gyan, Ben, Valim, Clarissa, and Daubenberger, Claudia

Subjects
3. Good health

99. Optimization of incubation conditions of <italic>Plasmodium falciparum</italic> antibody multiplex assays to measure IgG, IgG1–4, IgM and IgE using standard and customized reference pools for sero-epidemiological and vaccine studies.

Author

Ubillos, Itziar, Jiménez, Alfons, Vidal, Marta, Bowyer, Paul W., Gaur, Deepak, Dutta, Sheetij, Gamain, Benoit, Coppel, Ross, Chauhan, Virander, Lanar, David, Chitnis, Chetan, Angov, Evelina, Beeson, James, Cavanagh, David, Campo, Joseph J., Aguilar, Ruth, and Dobaño, Carlota

Subjects
MALARIA diagnosis, MALARIA vaccines, PLASMODIUM falciparum, IMMUNOGLOBULIN G, DIAGNOSTIC reagents & test kits
Abstract

Background: The quantitative suspension array technology (qSAT) is a useful platform for malaria immune marker discovery. However, a major challenge for large sero-epidemiological and malaria vaccine studies is the comparability across laboratories, which requires the access to standardized control reagents for assay optimization, to monitor performance and improve reproducibility. Here, the Plasmodium falciparum antibody reactivities of the newly available WHO reference reagent for anti-malaria human plasma (10/198) and of additional customized positive controls were examined with seven in-house qSAT multiplex assays measuring IgG, IgG1–4 subclasses, IgM and IgE against a panel of 40 antigens. The different positive controls were tested at different incubation times and temperatures (4 °C overnight, 37 °C 2 h, room temperature 1 h) to select the optimal conditions. Results: Overall, the WHO reference reagent had low IgG2, IgG4, IgM and IgE, and also low anti-CSP antibody levels, thus this reagent was enriched with plasmas from RTS,S-vaccinated volunteers to be used as standard for CSP-based vaccine studies. For the IgM assay, another customized plasma pool prepared with samples from malaria primo-infected adults with adequate IgM levels proved to be more adequate as a positive control. The range and magnitude of IgG and IgG1–4 responses were highest when the WHO reference reagent was incubated with antigen-coupled beads at 4 °C overnight. IgG levels measured in the negative control did not vary between incubations at 37 °C 2 h and 4 °C overnight, indicating no difference in unspecific binding. Conclusions: With this study, the immunogenicity profile of the WHO reference reagent, including seven immunoglobulin isotypes and subclasses, and more P. falciparum antigens, also those included in the leading RTS,S malaria vaccine, was better characterized. Overall, incubation of samples at 4 °C overnight rendered the best performance for antibody measurements against the antigens tested. Although the WHO reference reagent performed well to measure IgG to the majority of the common P. falciparum blood stage antigens tested, customized pools may need to be used as positive controls depending on the antigens (e.g. pre-erythrocytic proteins of low natural immunogenicity) and isotypes/subclasses (e.g. IgM) under study. [ABSTRACT FROM AUTHOR]

Published
2018
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100. The 2022 Vaccines Against Shigella and Enterotoxigenic Escherichia coli (VASE) Conference: Summary of breakout workshops.

Author

Baqar, Shahida, Bonavia, Aurelio, Louis Bourgeois, A., Campo, Joseph J., Clifford, Allison, Hanevik, Kurt, Hasso-Agopsowicz, Mateusz, Hausdorff, William, Kaminski, Robert, MacLennan, Calman A., Mantis, Nicholas, Martin, Laura B., Omore, Richard, Pasetti, Marcela, Pavlinac, Patricia, Phalipon, Armelle, Poly, Frédéric, Porter, Chad, Ramasamy, Maheshi N., and Rogawski McQuade, Elizabeth T.

Subjects
*SHIGELLA, *ESCHERICHIA coli, *SHIGELLOSIS, *COMBINED vaccines, *VACCINE effectiveness
Abstract

• Economic evaluations of enteric vaccine impact will help guide health investments. • Advancing adjuvant-vaccine combinations to human clinical trials is critical. • Emerging enteric pathogens like iNTS and Campylobacter need further advocacy. • New tools for characterizing inflammation are needed to improve health outcomes. • New technology to characterize adaptive immunity makes more protective vaccines. The global public health nonprofit organization PATH hosted the third Vaccines Against Shigella and Enterotoxigenic Escherichia coli (VASE) Conference in Washington, DC, from November 29 to December 1, 2022. This international gathering focused on cutting-edge research related to the development of vaccines against neglected diarrheal pathogens including Shigella , enterotoxigenic Escherichia coli (ETEC), Campylobacter , and non-typhoidal Salmonella. In addition to the conference's plenary content, the agenda featured ten breakout workshops on topics of importance to the enteric vaccine field. This unique aspect of VASE Conferences allows focused groups of attendees to engage in in-depth discussions on subjects of interest to the enteric vaccine development community. In 2022, the workshops covered a range of topics. Two focused on the public health value of enteric vaccines, with one examining how to translate evidence into policy and the other on the value proposition of potential combination vaccines against bacterial enteric pathogens. Two more workshops explored new tools for the development and evaluation of vaccines, with the first on integrating antigen/antibody technologies for mucosal vaccine and immunoprophylactic development, and the second on adjuvants specifically for Shigella vaccines for children in low- and middle-income countries. Another pair of workshops covered the status of vaccines against two emerging enteric pathogens, Campylobacter and invasive non-typhoidal Salmonella. The remaining four workshops examined the assessment of vaccine impact on acute and long-term morbidity. These included discussions on the nature and severity of intestinal inflammation; cellular immunity and immunological memory in ETEC and Shigella infections; clinical and microbiologic endpoints for Shigella vaccine efficacy studies in children; and intricacies of protective immunity to enteric pathogens. This article provides a brief summary of the presentations and discussions at each workshop in order to share these sessions with the broader enteric vaccine field. [ABSTRACT FROM AUTHOR]

Published
2024
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