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2. Development of an improved blood-stage malaria vaccine targeting the essential RH5-CyRPA-RIPR invasion complex

Author

Williams, Barnabas G., King, Lloyd D. W., Pulido, David, Quinkert, Doris, Lias, Amelia M., Silk, Sarah E., Ragotte, Robert J., Davies, Hannah, Barrett, Jordan R., McHugh, Kirsty, Rigby, Cassandra A., Alanine, Daniel G. W., Barfod, Lea, Shea, Michael W., Cowley, Li An, Dabbs, Rebecca A., Pattinson, David J., Douglas, Alexander D., Lyth, Oliver R., Illingworth, Joseph J., Jin, Jing, Carnrot, Cecilia, Kotraiah, Vinayaka, Christen, Jayne M., Noe, Amy R., MacGill, Randall S., King, C. Richter, Birkett, Ashley J., Soisson, Lorraine A., Skinner, Katherine, Miura, Kazutoyo, Long, Carole A., Higgins, Matthew K., and Draper, Simon J.

Published
2024
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3. Blood-stage malaria vaccine candidate RH5.1/Matrix-M in healthy Tanzanian adults and children; an open-label, non-randomised, first-in-human, single-centre, phase 1b trial

Author

Silk, Sarah E, Kalinga, Wilmina F, Salkeld, Jo, Mtaka, Ivanny M, Ahmed, Saumu, Milando, Florence, Diouf, Ababacar, Bundi, Caroline K, Balige, Neema, Hassan, Omar, Mkindi, Catherine G, Rwezaula, Stella, Athumani, Thabit, Mswata, Sarah, Lilolime, Nasoro S, Simon, Beatus, Msami, Hania, Mohamed, Mohamed, David, Damiano M, Mohammed, Latipha, Nyaulingo, Gloria, Mwalimu, Bakari, Juma, Omary, Mwamlima, Tunu G, Sasamalo, Ibrahim A, Mkumbange, Rose P, Kamage, Janeth J, Barrett, Jordan R, King, Lloyd D W, Hou, Mimi M, Pulido, David, Carnrot, Cecilia, Lawrie, Alison M, Cowan, Rachel E, Nugent, Fay L, Roberts, Rachel, Cho, Jee-Sun, Long, Carole A, Nielsen, Carolyn M, Miura, Kazutoyo, Draper, Simon J, Olotu, Ally I, and Minassian, Angela M

Published
2024
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4. Natural malaria infection elicits rare but potent neutralizing antibodies to the blood-stage antigen RH5

Author

Wang, Lawrence T., Cooper, Andrew J.R., Farrell, Brendan, Miura, Kazutoyo, Diouf, Ababacar, Müller-Sienerth, Nicole, Crosnier, Cécile, Purser, Lauren, Kirtley, Payton J., Maciuszek, Maciej, Barrett, Jordan R., McHugh, Kirsty, Ogwang, Rodney, Tucker, Courtney, Li, Shanping, Doumbo, Safiatou, Doumtabe, Didier, Pyo, Chul-Woo, Skinner, Jeff, Nielsen, Carolyn M., Silk, Sarah E., Kayentao, Kassoum, Ongoiba, Aissata, Zhao, Ming, Nguyen, Doan C., Lee, F. Eun-Hyung, Minassian, Angela M., Geraghty, Daniel E., Traore, Boubacar, Seder, Robert A., Wilder, Brandon K., Crompton, Peter D., Wright, Gavin J., Long, Carole A., Draper, Simon J., Higgins, Matthew K., and Tan, Joshua

Published
2024
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5. Analysis of the diverse antigenic landscape of the malaria protein RH5 identifies a potent vaccine-induced human public antibody clonotype

Author

Barrett, Jordan R., Pipini, Dimitra, Wright, Nathan D., Cooper, Andrew J.R., Gorini, Giacomo, Quinkert, Doris, Lias, Amelia M., Davies, Hannah, Rigby, Cassandra A., Aleshnick, Maya, Williams, Barnabas G., Bradshaw, William J., Paterson, Neil G., Martinson, Thomas, Kirtley, Payton, Picard, Luc, Wiggins, Christine D., Donnellan, Francesca R., King, Lloyd D.W., Wang, Lawrence T., Popplewell, Jonathan F., Silk, Sarah E., de Ruiter Swain, Jed, Skinner, Katherine, Kotraiah, Vinayaka, Noe, Amy R., MacGill, Randall S., King, C. Richter, Birkett, Ashley J., Soisson, Lorraine A., Minassian, Angela M., Lauffenburger, Douglas A., Miura, Kazutoyo, Long, Carole A., Wilder, Brandon K., Koekemoer, Lizbé, Tan, Joshua, Nielsen, Carolyn M., McHugh, Kirsty, and Draper, Simon J.

Published
2024
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12. A randomized first-in-human phase I trial of differentially adjuvanted Pfs48/45 malaria vaccines in Burkinabe adults

Author

Tiono, Alfred B., Plieskatt, Jordan L., Ouedraogo, Alphonse, Soulama, Ben Idriss, Miura, Kazutoyo, Bougouma, Edith C., Naghizadeh, Mohammad, Barry, Aissata, Yaro, Jean Baptist B., Ezinmegnon, Sem, Henry, Noelie, Ofori, Ebenezer Addo, Adu, Bright, Singh, Susheel K., Konkobo, Augustin, Bengtsson, Karin Lovgren, Diarra, Amidou, Carnrot, Cecilia, Reimer, Jenny M., Ouedraogo, Amidou, Tienta, Moussa, Long, Carole A., Ouedraogo, Issa N., Sagara, Issaka, Sirima, Sodiomon B., and Theisen, Michael

Subjects
United States. National Institute of Allergy and Infectious Diseases, Medical research, Medicine, Experimental, Malaria vaccine -- Product development, Glutamate -- Product development, Amino acids -- Product development, Antigens, Clinical trials, Malaria, Adults, Vaccines -- Product development, Immunoglobulin G, Plasmodium falciparum, Health care industry
Abstract

BACKGROUND. Malaria transmission-blocking vaccines aim to interrupt the transmission of malaria from one person to another. METHODS. The candidates R0.6C and ProC6C share the 6C domain of the Plasmodium falciparum sexual-stage antigen Pfs48/45. R0.6C utilizes the glutamate-rich protein (GLURP) as a carrier, and ProC6C includes a second domain (Pfs230-Pro) and a short 36-amino acid circumsporozoite protein (CSP) sequence. Healthy adults (n = 125) from a malaria-endemic area of Burkina Faso were immunized with 3 intramuscular injections, 4 weeks apart, of 30 [micro]g or 100 [micro]g R0.6C or ProC6C each adsorbed to Alhydrogel (AlOH) adjuvant alone or in combination with Matrix-M (15 [micro]g or 50 [micro]g, respectively). The allocation was random and double-blind for this phase I trial. RESULTS. The vaccines were safe and well tolerated with no vaccine-related serious adverse events. A total of 7 adverse events, mild to moderate in intensity and considered possibly related to the study vaccines, were recorded. Vaccine-specific antibodies were highest in volunteers immunized with 100 [micro]g ProC6C-AlOH with Matrix-M, and 13 of 20 (65%) individuals in the group showed greater than 80% transmission-reducing activity (TRA) when evaluated in the standard membrane feeding assay at 15 mg/mL IgG. In contrast, R0.6C induced sporadic TRA. CONCLUSION. All formulations were safe and well tolerated in a malaria-endemic area of Africa in healthy adults. The ProC6C-AlOH/ Matrix-M vaccine elicited the highest levels of functional antibodies, meriting further investigation. TRIAL REGISTRATION. Pan-African Clinical Trials Registry (https://pactr.samrc.ac.za) PACTR202201848463189. FUNDING. The study was funded by the European and Developing Countries Clinical Trials Partnership (grant RIA2018SV-2311)., Introduction Plasmodium falciparum malaria is transmitted by mosquitoes of the genus Anopheles. During a blood meal from an infected person, the female mosquito ingests sexual-stage parasites, which fertilize in the [...]

Published
2024
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14. Superior antibody immunogenicity of a viral-vectored RH5 blood-stage malaria vaccine in Tanzanian infants as compared to adults

Author

Silk, Sarah E., Kalinga, Wilmina F., Mtaka, Ivanny M., Lilolime, Nasoro S., Mpina, Maximillian, Milando, Florence, Ahmed, Saumu, Diouf, Ababacar, Mkwepu, Fatuma, Simon, Beatus, Athumani, Thabit, Rashid, Mohammed, Mohammed, Latipha, Lweno, Omary, Ali, Ali M., Nyaulingo, Gloria, Mwalimu, Bakari, Mswata, Sarah, Mwamlima, Tunu G., Barrett, Jordan R., Wang, Lawrence T., Themistocleous, Yrene, King, Lloyd D.W., Hodgson, Susanne H., Payne, Ruth O., Nielsen, Carolyn M., Lawrie, Alison M., Nugent, Fay L., Cho, Jee-Sun, Long, Carole A., Miura, Kazutoyo, Draper, Simon J., Minassian, Angela M., and Olotu, Ally I.

Published
2023
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18. Safety, tolerability, and Plasmodium falciparum transmission-reducing activity of monoclonal antibody TB31F: a single-centre, open-label, first-in-human, dose-escalation, phase 1 trial in healthy malaria-naive adults

Author

van der Boor, Saskia C, Smit, Merel J, van Beek, Stijn W, Ramjith, Jordache, Teelen, Karina, van de Vegte-Bolmer, Marga, van Gemert, Geert-Jan, Pickkers, Peter, Wu, Yimin, Locke, Emily, Lee, Shwu-Maan, Aponte, John, King, C Richter, Birkett, Ashley J, Miura, Kazutoyo, Ayorinde, Morolayo A, Sauerwein, Robert W, ter Heine, Rob, Ockenhouse, Christian F, Bousema, Teun, Jore, Matthijs M, and McCall, Matthew B B

Published
2022
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24. Interim safety and immunogenicity analysis of the EuCorVac‐19 COVID‐19 vaccine in a Phase 3 randomized, observer‐blind, immunobridging trial in the Philippines.

Author

Lovell, Jonathan F., Miura, Kazutoyo, Baik, Yeong Ok, Lee, Chankyu, Choi, YoungJin, Her, Howard, Lee, Jeong‐Yoon, Ylade, Michelle, Lee‐Llacer, Roxas, De Asis, Norman, Trinidad‐Aseron, Mitzi, Ranola, Jose Manuel, and De Jesus, Loreta Zoleta

Abstract

EuCorVac‐19 (ECV‐19) is a recombinant receptor binding domain (RBD) COVID‐19 vaccine that displays the RBD (derived from the SARS‐CoV‐2 Wuhan strain) on immunogenic liposomes. This study compares the safety and immunogenicity of ECV‐19 to the COVISHIELDTM (CS) adenoviral‐vectored vaccine. Interim analysis is presented of a randomized, observer‐blind, immunobridging Phase 3 trial in the Philippines in 2600 subjects, with treatment and biospecimen collection between October 2022 and January 2023. Healthy male and female adults who received investigational vaccines were 18 years and older, and randomly assigned to ECV‐19 (n = 2004) or CS (n = 596) groups. Immunization followed a two‐injection, intramuscular regimen with 4 weeks between prime and boost vaccination. Safety endpoints were assessed in all participants and immunogenicity analysis was carried out in a subset (n = 585 in ECV‐19 and n = 290 in CS groups). The primary immunological endpoints were superiority of neutralizing antibody response, as well as noninferiority in seroresponse rate (defined as a 4‐fold increase in RBD antibody titers from baseline). After prime vaccination, ECV‐19 had a lower incidence of local solicited adverse events (AEs) (12.0% vs. 15.8%, p < 0.01), and solicited systemic AEs (13.1 vs. 17.4%, p < 0.01) relative to CS. After the second injection, both ECV‐19 and CS had lower overall solicited AEs (7.8% vs. 7.6%). For immunological assessment, 98% of participants had prior COVID‐19 exposure (based on the presence of anti‐nucleocapsid antibodies) at the time of the initial immunization, without differing baseline antibody levels or microneutralization (MN) titers against the Wuhan strain in the two groups. After prime vaccination, ECV‐19 induced higher anti‐RBD IgG relative to CS (1,464 vs. 355 BAU/mL, p < 0.001) and higher neutralizing antibody response (1,303 vs. 494 MN titer, p < 0.001). After boost vaccination, ECV‐19 and CS maintained those levels of anti‐RBD IgG (1367 vs. 344 BAU/mL, p < 0.001) and neutralizing antibodies (1128 vs. 469 MN titer, p < 0.001). ECV‐19 also elicited antibodies that better neutralized the Omicron variant, compared to CS (763 vs. 373 MN titer, p < 0.001). Women displayed higher responses to both vaccines than men. The ECV‐19 group had a greater seroresponse rate compared to CS (83% vs. 30%, p < 0.001). In summary, both ECV‐19 and CS had favorable safety profiles, with ECV‐19 showing diminished local and systemic solicited AE after prime immunization. ECV‐19 had significantly greater immunogenicity in terms of anti‐RBD IgG, neutralizing antibodies, and seroresponse rate. These data establish a relatively favorable safety and immunogenicity profile for ECV‐19. The trial is registered on ClinicalTrials.gov (NCT05572879). [ABSTRACT FROM AUTHOR]

Published
2024
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25. Antibody gene features associated with binding and functional activity in malaria vaccine-derived human mAbs.

Author

Coelho, Camila H., Marquez, Susanna, Nguemwo Tentokam, Bergeline C., Berhe, Anne D., Miura, Kazutoyo, Rao, Vishal N., Long, Carole A., Doumbo, Ogobara K., Sagara, Issaka, Healy, Sara, Kleinstein, Steven H., and Duffy, Patrick E.

Subjects
ANTIBODY diversity, MALARIA vaccines, MONOCLONAL antibodies, MALARIA, GERM cells
Abstract

The impact of adjuvants on malaria vaccine-induced antibody repertoire is poorly understood. Here, we characterize the impact of two adjuvants, Alhydrogel® and AS01, on antibody clonotype diversity, binding and function, post malaria vaccination. We expressed 132 recombinant anti-Pfs230D1 human monoclonal antibodies (mAbs) from participants immunized with malaria transmission-blocking vaccine Pfs230D1, formulated with either Alhydrogel® or AS01. Anti-Pfs230D1 mAbs generated by Alhydrogel® formulation showed higher binding frequency to Pfs230D1 compared to AS01 formulation, although the frequency of functional mAbs was similar between adjuvant groups. Overall, the AS01 formulation induced anti-Pfs230D1 functional antibodies from a broader array of germline sequences versus the Alhydrogel® formulation. All mAbs using IGHV1-69 gene from the Alhydrogel® cohort bound to recombinant Pfs230D1, but did not block parasite transmission to mosquitoes, similar to the IGHV1-69 mAbs isolated from the AS01 cohort. These findings may help inform vaccine design and adjuvant selection for immunization with Plasmodium antigens. [ABSTRACT FROM AUTHOR]

Published
2024
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26. Cross-reactivity of rPvs48/45, a recombinant Plasmodium vivax protein, with sera from Plasmodium falciparum endemic areas of Africa

Author

Arévalo-Herrera, Myriam, primary, Balam, Saidou, additional, Miura, Kazutoyo, additional, Ayadi, Imen, additional, Konaté, Drissa, additional, Incandela, Nathan C., additional, Agnolon, Valentina, additional, Guindo, Merepen A, additional, Diakité, Seidina A.S., additional, Olugbile, Sope, additional, Nebie, Issa, additional, Herrera, Sonia M, additional, Long, Carole, additional, Kajava, Andrey V., additional, Diakité, Mahamadou, additional, Corradin, Giampietro, additional, and Herrera, Socrates, additional

Published
2024
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27. First Phase 1b, single-center, age de-escalation trial of theP. falciparumblood-stage malaria vaccine candidate RH5.1/Matrix-M™: a delayed boost regimen induces high levels of functional antibodies in 5-17 month old Tanzanian infants

Author

Silk, Sarah E., primary, Kalinga, Wilmina F., additional, Salkeld, Jo, additional, Mtaka, Ivanny M., additional, Ahmed, Saumu, additional, Milando, Florence, additional, Diouf, Ababacar, additional, Bundi, Caroline K., additional, Balige, Neema, additional, Hassan, Omar, additional, Mkindi, Catherine G., additional, Rwezaula, Stella, additional, Athumani, Thabit, additional, Mswata, Sarah, additional, Lilolime, Nasoro S., additional, Simon, Beatus, additional, Msami, Hania, additional, Mohamed, Mohamed, additional, David, Damiano M., additional, Mohammed, Latipha, additional, Nyaulingo, Gloria, additional, Mwalimu, Bakari, additional, Juma, Omary, additional, Mwamlima, Tunu G., additional, Sasamalo, Ibrahim A., additional, Mkumbange, Rose P., additional, Kamage, Janeth J., additional, Barrett, Jordan R., additional, King, Lloyd D. W., additional, Hou, Mimi M., additional, Pulido, David, additional, Carnrot, Cecilia, additional, Lawrie, Alison M., additional, Cowan, Rachel E., additional, Nugent, Fay L., additional, Roberts, Rachel, additional, Cho, Jee-Sun, additional, Long, Carole A., additional, Nielsen, Carolyn M., additional, Miura, Kazutoyo, additional, Draper, Simon J., additional, Olotu, Ally I., additional, and Minassian, Angela M., additional

Published
2024
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29. Reduced blood-stage malaria growth and immune correlates in humans following RH5 vaccination

Author

Minassian, Angela M., Silk, Sarah E., Barrett, Jordan R., Nielsen, Carolyn M., Miura, Kazutoyo, Diouf, Ababacar, Loos, Carolin, Fallon, Jonathan K., Michell, Ashlin R., White, Michael T., Edwards, Nick J., Poulton, Ian D., Mitton, Celia H., Payne, Ruth O., Marks, Michael, Maxwell-Scott, Hector, Querol-Rubiera, Antonio, Bisnauthsing, Karen, Batra, Rahul, Ogrina, Tatiana, Brendish, Nathan J., Themistocleous, Yrene, Rawlinson, Thomas A., Ellis, Katherine J., Quinkert, Doris, Baker, Megan, Lopez Ramon, Raquel, Ramos Lopez, Fernando, Barfod, Lea, Folegatti, Pedro M., Silman, Daniel, Datoo, Mehreen, Taylor, Iona J., Jin, Jing, Pulido, David, Douglas, Alexander D., de Jongh, Willem A., Smith, Robert, Berrie, Eleanor, Noe, Amy R., Diggs, Carter L., Soisson, Lorraine A., Ashfield, Rebecca, Faust, Saul N., Goodman, Anna L., Lawrie, Alison M., Nugent, Fay L., Alter, Galit, Long, Carole A., and Draper, Simon J.

Published
2021
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30. Protein/AS01B vaccination elicits stronger, more Th2-skewed antigen-specific human T follicular helper cell responses than heterologous viral vectors

Author

Nielsen, Carolyn M., Ogbe, Ane, Pedroza-Pacheco, Isabela, Doeleman, Susanne E., Chen, Yue, Silk, Sarah E., Barrett, Jordan R., Elias, Sean C., Miura, Kazutoyo, Diouf, Ababacar, Bardelli, Martino, Dabbs, Rebecca A., Barfod, Lea, Long, Carole A., Haynes, Barton F., Payne, Ruth O., Minassian, Angela M., Bradley, Todd, Draper, Simon J., and Borrow, Persephone

Published
2021
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31. A Self-Assembling Pfs230D1-Ferritin Nanoparticle Vaccine Has Potent and Durable Malaria Transmission-Reducing Activity.

Author

Salinas, Nichole D., Ma, Rui, McAleese, Holly, Ouahes, Tarik, Long, Carole A., Miura, Kazutoyo, Lambert, Lynn E., and Tolia, Niraj H.

Subjects
NANOPARTICLES, MALARIA vaccines, MALARIA, MOSQUITO vectors, MALARIA prevention, HELICOBACTER pylori infections, TRICHOMONIASIS
Abstract

Malaria is caused by eukaryotic protozoan parasites of the genus Plasmodium. There are 249 million new cases and 608,000 deaths annually, and new interventions are desperately needed. Malaria vaccines can be divided into three categories: liver stage, blood stage, or transmission-blocking vaccines. Transmission-blocking vaccines prevent the transmission of disease by the mosquito vector from one human to another. Pfs230 is one of the leading transmission-blocking vaccine antigens for malaria. Here, we describe the development of a 24-copy self-assembling nanoparticle vaccine comprising domain 1 of Pfs230 genetically fused to H. pylori ferritin. The single-component Pfs230D1-ferritin construct forms a stable and homogenous 24-copy nanoparticle with good production yields. The nanoparticle is highly immunogenic, as two low-dose vaccinations of New Zealand White rabbits elicited a potent and durable antibody response with high transmission-reducing activity when formulated in two distinct adjuvants suitable for translation to human use. This single-component 24-copy Pfs230D1-ferritin nanoparticle vaccine has the potential to improve production pipelines and the cost of manufacturing a potent and durable transmission-blocking vaccine for malaria control. [ABSTRACT FROM AUTHOR]

Published
2024
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32. A randomized first-in-human Phase 1 trial of differentially adjuvanted Pfs48/45 malaria vaccines in Burkinabé adults

Author

Tiono, B. Alfred, primary, Plieskatt, Jordan L., additional, Ouedraogo, Alphonse, additional, Soulama, Ben Idriss, additional, Miura, Kazutoyo, additional, Bougouma, Edith C., additional, Naghizadeh, Mohammad, additional, Barry, Aissata, additional, Yaro, Jean Baptiste B., additional, Ezinmegnon, Sem, additional, Henry, Noelie B., additional, Ofori, Ebenezer, additional, Adu, Bright, additional, Singh, Susheel K., additional, Konkobo, Augustin, additional, Lövgren Bengtsson, Karin, additional, Diarra, Amidou, additional, Carnrot, Cecilia, additional, Reimer, Jenny M., additional, Ouedraogo, Amidou Z., additional, Tienta, Moussa, additional, Long, Carole A., additional, Nebie, Issa N., additional, Sagara, Issaka, additional, Sirima, Sodiomon B., additional, and Theisen, Michael, additional

Published
2024
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33. Evaluation of Precision of thePlasmodium knowlesiGrowth Inhibition Assay forPlasmodium vivaxDuffy-Binding Protein-based Malaria Vaccine Development

Author

Mertens, Jonas E, primary, Rigby, Cassandra A, additional, Bardelli, Martino, additional, Quinkert, Doris, additional, Hou, Mimi M, additional, Diouf, Ababacar, additional, Silk, Sarah E, additional, Chitnis, Chetan E, additional, Minassian, Angela M, additional, Moon, Robert W, additional, Long, Carole A, additional, Draper, Simon J, additional, and Miura, Kazutoyo, additional

Published
2024
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34. Preclinical Development of a Stabilized RH5 Virus-Like Particle Vaccine that Induces Improved Anti-Malarial Antibodies

Author

King, Lloyd D W, primary, Pulido, David, additional, Barrett, Jordan R, additional, Davies, Hannah, additional, Quinkert, Doris, additional, Lias, Amelia M, additional, Silk, Sarah E, additional, Pattinson, David J, additional, Diouf, Ababacar, additional, Williams, Barnabas G, additional, McHugh, Kirsty, additional, Rodrigues, Ana, additional, Rigby, Cassandra A, additional, Strazza, Veronica, additional, Suurbaar, Jonathan, additional, Rees-Spear, Chloe, additional, Dabbs, Rebecca A, additional, Ishizuka, Andrew S, additional, Zhou, Yu, additional, Gupta, Gaurav, additional, Jin, Jing, additional, Li, Yuanyuan, additional, Carnrot, Cecilia, additional, Minassian, Angela M, additional, Campeotto, Ivan, additional, Fleishman, Sarel J, additional, Noe, Amy R, additional, MacGill, Randall S, additional, King, C Richter, additional, Birkett, Ashley J, additional, Soisson, Lorraine A, additional, Long, Carole A, additional, Miura, Kazutoyo, additional, Ashfield, Rebecca, additional, Skinner, Katherine, additional, Howarth, Mark, additional, Biswas, Sumi, additional, and Draper, Simon J, additional

Published
2024
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36. OA-344 Clinical development in Burkina Faso of novel malaria vaccines based on the Pfs48/45 antigen

Author

Ouedraogo, Alphonse, primary, Plieskatt, Jordan, additional, Ouedraogo, Issa N, additional, Soulama, Ben Idriss, additional, Ezinmegon, Sem, additional, Miura, Kazutoyo, additional, Naghizadeh, Mohammad, additional, Ofori, Ebenezer, additional, Diarra, Amidou, additional, Henry, Noelie, additional, Zéguimé, Amatigué, additional, Bengtsson, Karin Lövgren, additional, Reimer, Jenny M, additional, Long, Carole, additional, Sagara, Issaka, additional, Sirima, Sodiomon B, additional, Tiono, Alfred B, additional, and Thesien, Michael, additional

Published
2023
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37. Naturally acquired transmission-blocking immunity against different strains of Plasmodium vivax in a malaria endemic area in Thailand

Author

Thongpoon, Sataporn, primary, Roobsoong, Wanlapa, additional, Nguitragool, Wang, additional, Chotirat, Sadudee, additional, Tsuboi, Takafumi, additional, Takashima, Eizo, additional, Cui, Liwang, additional, Ishino, Tomoko, additional, Tachibana, Mayumi, additional, Miura, Kazutoyo, additional, and Sattabongkot, Jetsumon, additional

Published
2023
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38. Artemisinin resistance phenotypes and K13 inheritance in a Plasmodium falciparum cross and Aotus model

Author

Sá, Juliana M., Kaslow, Sarah R., Krause, Michael A., Melendez-Muniz, Viviana A., Salzman, Rebecca E., Kite, Whitney A., Zhang, Min, Barros, Roberto R. Moraes, Mu, Jianbing, Han, Paul K., Mershon, J. Patrick, Figan, Christine E., Caleon, Ramoncito L., Rahman, Rifat S., Gibson, Tyler J., Amaratunga, Chanaki, Nishiguchi, Erika P., Breglio, Kimberly F., Engels, Theresa M., Velmurugan, Soundarapandian, Ricklefs, Stacy, Straimer, Judith, Gnädig, Nina F., Deng, Bingbing, Liu, Anna, Diouf, Ababacar, Miura, Kazutoyo, Tullo, Gregory S., Eastman, Richard T., Chakravarty, Sumana, James, Eric R., Udenze, Kenneth, Li, Suzanne, Sturdevant, Daniel E., Gwadz, Robert W., Porcella, Stephen F., Long, Carole A., Fidock, David A., Thomas, Marvin L., Fay, Michael P., Sim, B. Kim Lee, Hoffman, Stephen L., Adams, John H., Fairhurst, Rick M., Su, Xin-zhuan, and Wellems, Thomas E.

Published
2018

39. Autoantibodies inhibit Plasmodium falciparum growth and are associated with protection from clinical malaria

Author

Hagadorn, Kelly A., Peterson, Mary E., Kole, Hemanta, Scott, Bethany, Skinner, Jeff, Diouf, Ababacar, Takashima, Eizo, Ongoiba, Aissata, Doumbo, Safiatou, Doumtabe, Didier, Li, Shanping, Sekar, Padmapriya, Yan, Mei, Zhu, Chengsong, Nagaoka, Hikaru, Kanoi, Bernard N., Li, Quan-Zhen, Long, Carole, Long, Eric O., Kayentao, Kassoum, Jenks, Scott A., Sanz, Ignacio, Tsuboi, Takafumi, Traore, Boubacar, Bolland, Silvia, Miura, Kazutoyo, Crompton, Peter D., and Hopp, Christine S.

Published
2024
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40. Naturally acquired antibodies specific for Plasmodium falciparum reticulocyte-binding protein homologue 5 inhibit parasite growth and predict protection from malaria.

Author

Tran, Tuan, Ongoiba, Aissata, Coursen, Jill, Crosnier, Cecile, Diouf, Ababacar, Huang, Chiung-Yu, Li, Shanping, Doumbo, Safiatou, Doumtabe, Didier, Kone, Younoussou, Bathily, Aboudramane, Dia, Seydou, Niangaly, Moussa, Dara, Charles, Sangala, Jules, Miller, Louis, Doumbo, Ogobara, Kayentao, Kassoum, Long, Carole, Miura, Kazutoyo, Wright, Gavin, Traore, Boubacar, and Crompton, Peter

Subjects
Plasmodium falciparum, RH5, blood-stage immunity, endemic population, malaria, prospective cohort study, Adolescent, Adult, Antibodies, Protozoan, Carrier Proteins, Child, Child, Preschool, Female, Humans, Immunoglobulin G, Infant, Malaria Vaccines, Malaria, Falciparum, Male, Placenta, Plasmodium falciparum, Pregnancy, Reticulocytes, Young Adult
Abstract

BACKGROUND: Plasmodium falciparum reticulocyte-binding protein homologue 5 (PfRH5) is a blood-stage parasite protein essential for host erythrocyte invasion. PfRH5-specific antibodies raised in animals inhibit parasite growth in vitro, but the relevance of naturally acquired PfRH5-specific antibodies in humans is unclear. METHODS: We assessed pre-malaria season PfRH5-specific immunoglobulin G (IgG) levels in 357 Malian children and adults who were uninfected with Plasmodium. Subsequent P. falciparum infections were detected by polymerase chain reaction every 2 weeks and malaria episodes by weekly physical examination and self-referral for 7 months. The primary outcome was time between the first P. falciparum infection and the first febrile malaria episode. PfRH5-specific IgG was assayed for parasite growth-inhibitory activity. RESULTS: The presence of PfRH5-specific IgG at enrollment was associated with a longer time between the first blood-stage infection and the first malaria episode (PfRH5-seropositive median: 71 days, PfRH5-seronegative median: 18 days; P = .001). This association remained significant after adjustment for age and other factors associated with malaria risk/exposure (hazard ratio, .62; P = .02). Concentrated PfRH5-specific IgG purified from Malians inhibited P. falciparum growth in vitro. CONCLUSIONS: Naturally acquired PfRH5-specific IgG inhibits parasite growth in vitro and predicts protection from malaria. These findings strongly support efforts to develop PfRH5 as an urgently needed blood-stage malaria vaccine. CLINICAL TRIALS REGISTRATION: NCT01322581.

Published
2014

41. Naturally Acquired Transmission-Blocking Immunity Against Different Strains of Plasmodium vivax in a Malaria-Endemic Area in Thailand.

Author

Thongpoon, Sataporn, Roobsoong, Wanlapa, Nguitragool, Wang, Chotirat, Sadudee, Tsuboi, Takafumi, Takashima, Eizo, Cui, Liwang, Ishino, Tomoko, Tachibana, Mayumi, Miura, Kazutoyo, and Sattabongkot, Jetsumon

Subjects
PLASMODIUM vivax, IMMUNITY, NATURAL immunity, ARBOVIRUSES, PLASMODIUM, VACCINE development, TRYPANOSOMA
Abstract

Background Human immunity triggered by natural malaria infections impedes parasite transmission from humans to mosquitoes, leading to interest in transmission-blocking vaccines. However, immunity characteristics, especially strain specificity, remain largely unexplored. We investigated naturally acquired transmission-blocking immunity (TBI) against Plasmodium vivax , a major malaria parasite. Methods Using the direct membrane-feeding assay, we assessed TBI in plasma samples and examined the role of antibodies by removing immunoglobulins through protein G/L adsorption before mosquito feeding. Strain specificity was evaluated by conducting a direct membrane-feeding assay with plasma exchange. Results Blood samples from 47 patients with P vivax were evaluated, with 37 plasma samples successfully infecting mosquitoes. Among these, 26 showed inhibition before immunoglobulin depletion. Despite substantial immunoglobulin removal, 4 samples still exhibited notable inhibition, while 22 had reduced blocking activity. Testing against heterologous strains revealed some plasma samples with broad TBI and others with strain-specific TBI. Conclusions Our findings indicate that naturally acquired TBI is mainly mediated by antibodies, with possible contributions from other serum factors. The transmission-blocking activity of plasma samples varied by the tested parasite strain, suggesting single polymorphic or multiple targets for naturally acquired TBI. These observations improve understanding of immunity against P vivax and hold implications for transmission-blocking vaccine development. [ABSTRACT FROM AUTHOR]

Published
2024
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42. Natural malaria infection elicits rare but potent neutralizing antibodies to the blood-stage antigen RH5

Author

Wang, Lawrence T., primary, Cooper, Andrew J.R., additional, Farrell, Brendan, additional, Miura, Kazutoyo, additional, Diouf, Ababacar, additional, Muller-Sienerth, Nicole, additional, Crosnier, Cecile, additional, Purser, Lauren, additional, Maciuszek, Maciej, additional, Barrett, Jordan R., additional, McHugh, Kirsty, additional, Tucker, Courtney, additional, Li, Shanping, additional, Doumbo, Safiatou, additional, Doumtabe, Didier, additional, Pyo, Chul-Woo, additional, Nielsen, Carolyn M., additional, Silk, Sarah E., additional, Kayentao, Kassoum, additional, Ongoiba, Aissata, additional, Zhao, Ming, additional, Nguyen, Doan C., additional, Lee, F. Eun-Hyung, additional, Minassian, Angela M., additional, Geraghty, Daniel E., additional, Traore, Boubacar, additional, Seder, Robert A., additional, Crompton, Peter D., additional, Wright, Gavin J., additional, Long, Carole A., additional, Draper, Simon J., additional, Higgins, Matthew K., additional, and Tan, Joshua, additional

Published
2023
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