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Malaria research: Malaria Clinical Trials Unit (MCTU) Lab

From left to right: Kristin Fürle, Veronika Rathay, Viktoria Kiehl and Richard Thomson Luque

Lab members

Richard Thomson Luque (scientific director, 2021 - present)

Kristin Fürle (senior technician, 2021 - present)

Viktoria Kiehl (technician, 2023 - present)

Catherine Mkindi (guest scientist, 2024)

Inken Rasmussen (MD student, 2024)

Veronika Rathay (MD student, 2023 - 2024)

Lea Woltereck (MSc rotation 2023)

Anne Ulmer (MD Thesis 2022-2023)

Arin Ali (QM 2022-2023)

Maximilian Winter (BSc Thesis 2022)

Julia Hibbert (PhD student 2022)

Micha Rosenkranz (PhD student with Prof. Dr. Faith Osier, 2021-2022)

Kalina Chavdarova (BSc Thesis 2021)

Natascha Osswald (BSc Thesis 2021)

from left to right: Richard Thomson Luque, Micha Rosenkranz, Anne Ulmer, Arin Ali, Julia Hibbert, Kristin Fürle

Research interest

Malaria is caused by parasites, which are transmitted by mosquito bites. The first target of the parasite after the infective bite is the liver. Massive multiplication of the parasite in the liver and its release into the blood stream leads to the blood stage of the infection, where parasites infect red blood cells. Here, they multiply again, subsequently killing the host cells and re-infecting new red blood cells. It is this blood stage cycle that causes all pathophysiological symptoms and frequently leads to death in unprotected, “naive“ individuals. The MCTU works side by side with Sumaya-Biotech GmbH &Co. KG in the development of effective malaria vaccines and medication complementary tools that seem essential in the goal of malaria erradication.

Projects

Sumaya Biotech´s malaria vaccine candidates are based on the full-length merozoite surface protein 1 (MSP1), which is involved in the invasion of red blood cells by the parasite and the release of daughter cells from the infected erythrocytes. MSP1 is further expressed during the liver stage of the parasite.

(previously SumayaVac1) is based on the full-length, recombinant, 196kDa MSP1 protein together with an adjuvant (GLA-SE) and was successfully tested in a first-in-human trial in Heidelberg. It was shown to be safe, well tolerated and immunogenic, with all vaccinees sero-converting. 

SUM-101 elicited antibodies were able to stimulate various Fc-mediated effector mechanisms associated with protection against malaria, including phagocytosis, release of reactive oxygen species, production of IFN-γ as well as complement activation and fixation. The multifunctional activity of the humoral immune response remained for at least 6 months after vaccination and was comparable to that of naturally acquired anti-MSP1 antibodies from semi-immune adults from Kenya. A second clinical trial performed in Tanzania on pre-exposed volunteers is currently ongoing.

is an Adenovirus expressing MSP-1 and is planned to be used together with SUM-101 in a prime-boost scheme. It has started regulatory toxicological studies.

Activities

At the XIV BioMalPar Conference taking place from 23-25 May 2023 at EMBL, Heidelberg, the MCTU presented a poster on the subject “Immunization with the Plasmodium falciparum full-length MSP1 malaria vaccine candidate SumayaVac-1 elicits multifunctional IgMs”.

Over the years the Malaria Meeting at the Bernhard Nocht Institute for Tropical Medicine has developed into a scientific event that is respected beyond the borders of Germany, where both clinicians and non-clinical natural scientists present their results on current malaria research, among others the MCTU in 2023.

We presented the latest results on SUM-101 (SumayaVac1) at the 20th International Congress for Tropical Medicine and Malaria (ICTMM) in Bangkok in October 2022. Our vaccine elicited FC-mediated effector functions through both IgG and IgM. Results on the high degree of multi-functionality of antibodies against the highly conserved N-terminal p83 subunit were discussed.  Notably, we showed the ability of SUM-101 to elicit a recall memory T cell response and induce cellular cytotoxicity through CD8+ T cells.

From 23 - 25 May 2022 the MCTU participated in the XVIII BioMalPar Conference on the Biology and Pathology of the Malaria Parasite at EMBL, Heidelberg. Richard Thomson Luque presented the results of the SUM-101 (SumavaVac1) first-in-human clinical trial and in particular introduced the latest results showing that IgG and IgM of vaccinees are capable of deploying a wide spectrum of long-lasting FC-mediated effector functions comparable to that of the natural immunity achieved by endemic exposed population.

List of publications

MCTU-related papers

Rathay V, Fürle K, Kiehl V, Ulmer A, Lanzer M, Thomson-Luque R. IgG Subclass Switch in Volunteers Repeatedly Immunized with the Full-Length Plasmodium falciparum Merozoite Surface Protein 1 (MSP1). Vaccines. 2024; 12(2):208. doi.org/10.3390/vaccines12020208

Thomson-Luque R, Stabler TC, Fürle K, Silva JC, Daubenberger C. Plasmodium falciparum merozoite surface protein 1 as asexual blood stage malaria vaccine candidate. Expert Rev Vaccines. 2024 Jan-Dec;23(1):160-173. doi: 10.1080/14760584.2023.2295430. Epub 2023 Dec 27. PMID: 38100310.

Rosenkranz M, Fürle K, Hibbert J, Ulmer A, Ali A, Giese T, Blank A, Haefeli WE, Böhnlein E, Lanzer M, Thomson-Luque R. Multifunctional IgG/IgM antibodies and cellular cytotoxicity are elicited by the full-length MSP1 SumayaVac-1 malaria vaccine. NPJ Vaccines. 2023 Aug 9;8(1):112. doi: 10.1038/s41541-023-00701-2. PMID: 37558673; PMCID: PMC10412566.

Blank, A., et al. Immunization with full-length Plasmodium falciparum merozoite surface protein 1 is safe and elicits functional cytophilic antibodies in a randomized first-in-human trial. NPJ Vaccines 5, 10 (2020).

2021

Thomson-Luque R, Votborg-Novél L, Ndovie W, Andrade CM, Niangaly M, Attipa C, Lima NF, Coulibaly D, Doumtabe D, Guindo B, Tangara B, Maiga F, Kone AK, Traore K, Kayentao K, Ongoiba A, Doumbo S, Thera MA, Traoré B, Seydel K, Osório NS, Portugal S. Plasmodium falciparum transcription in different clinical presentations of malaria associates with circulation time of infected erythrocytes. Nat Commun. 2021 Jul 30;12(1):4711. doi: 10.1038/s41467-021-25062-z. PMID: 34330920; PMCID: PMC8324851.

Thomson-Luque R, Bautista JM. Home Sweet Home: Plasmodium vivax-Infected Reticulocytes-The Younger the Better? Front Cell Infect Microbiol. 2021 May 13;11:675156. doi: 10.3389/fcimb.2021.675156. PMID: 34055670; PMCID: PMC8162270

2020

Andrade CM, Fleckenstein H, Thomson-Luque R, Doumbo S, Lima NF, Anderson C, Hibbert J, Hopp CS, Tran TM, Li S, Niangaly M, Cisse H, Doumtabe D, Skinner J, Sturdevant D, Ricklefs S, Virtaneva K, Asghar M, Homann MV, Turner L, Martins J, Allman EL, N'Dri ME, Winkler V, Llinás M, Lavazec C, Martens C, Färnert A, Kayentao K, Ongoiba A, Lavstsen T, Osório NS, Otto TD, Recker M, Traore B, Crompton PD, Portugal S. Increased circulation time of Plasmodium falciparum underlies persistent asymptomatic infection in the dry season. Nat Med. 2020 Dec;26(12):1929-1940. doi: 10.1038/s41591-020-1084-0. Epub 2020 Oct 26. PMID: 33106664

2019

Adapa SR, Taylor RA, Wang C, Thomson-Luque R, Johnson LR, Jiang RHY. Plasmodium vivax readiness to transmit: implication for malaria eradication. BMC Syst Biol. 2019;13(1):5. Published 2019 Jan 11. doi:10.1186/s12918-018-0669-4 Thomson-Luque R, Adams JH, Kocken CHM, Pasini EM. From marginal to essential: the golden thread between nutrient sensing, medium composition and Plasmodium vivax maturation in in vitro culture. Malar J. 2019;18(1):344. Published 2019 Oct 10. doi:10.1186/s12936-019-2949-x

2018

Richard Thomson-Luque, Chengqi Wang, Francis B. Ntumngia, Shulin X, Karoly Szekeres, Amy Conway, Swamy Rakesh Adapa, Samantha J. Barnes, John H. Adams and Rays H.Y. Jiang. In depth phenotypic characterization of reticulocyte maturation using mass cytometry. Blood Cells Molecules and Diseases July 2018. DOI: 10.1016/j.bcmd.2018.06.004

Alison Roth, Steven P. Maher, Amy J. Conway, Ratawan Ubalee, Victor Chaumeau, Chiara Andolina, Stephen A. Kaba, Amélie Vantaux, Malina A. Bakowski, Richard Thomson-Luque, Swamy Rakesh Adapa, Naresh Singh, Samantha J. Barnes, Caitlin A. Cooper, Mélanie Rouillier, Case W. McNamara, Sebastian A. Mikolajczak, Noah Sather, Benoît Witkowski, Brice Campo, Stefan H. I. Kappe, David E. Lanar, François Nosten, Silas Davidson, Rays H. Y. Jiang, Dennis E. Kyle, John H. Adams. A comprehensive model for assessment of liver stage therapies targeting Plasmodium vivax and Plasmodium falciparum. Nature Communications. 2018;9:1837. doi:10.1038/s41467-018-04221-9

Ntumngia FB, Thomson-Luque R, Galusic S, Frato G, Frischmann S, Peabody DS, Chackerian B, Ferreira MU, King CL, Adams JH. Identification and immunological charaterization of the ligand domain of Plasmodium vivax reticulocyte binding protein 1a. J Infect Dis. 2018 May 7

2017

Francis B. Ntumngia, Camilla V. Pires, Samantha J. Barnes, Miriam T. George, Richard Thomson-Luque, Flora S. Kano, Jessica R. S. Alves, Darya Urusova, Dhelio B. Pereira, Niraj H. Tolia, Christopher L. King, Luzia H. Carvalho, John H. Adams. An engineered vaccine of the Plasmodium vivax Duffy binding protein enhances induction of broadly neutralizing antibodies. Scientific Reports. 2017;7:13779. doi:10.1038/s41598-017-13891-2

Thomson-Luque R, Saliba, K. S., Kocken, C. H., & Pasini, E. M. “A Continuous, Long-Term Plasmodium Vivax In Vitro Blood-Stage Culture: What Are We Missing?” Trends in Parasitology, 2017, doi:10.1016/j.pt.2017.07.001

2016

Ntumngia FB, Thomson-Luque R, Torres L de M, Gunalan K, Carvalho LH, Adams JH. A Novel Erythrocyte Binding Protein of Plasmodium vivax Suggests an Alternate Invasion Pathway into Duffy-Positive Reticulocytes. mBio. 2016;7(4):e01261-16. doi:10.1128/mBio.01261-16

Shaw-Saliba K*, Thomson-Luque R*, Obaldía N, et al. Insights into an Optimization of Plasmodium vivax Sal-1 In Vitro Culture: The Aotus Primate Model. Sinnis P, ed. PLoS Neglected Tropical Diseases. 2016;10(7):e0004870. doi:10.1371/journal.pntd.0004870. *equally contributed.

2015

Leandro-Reguillo P, Thomson-Luque R, Monteiro WM, de Lacerda MV. Urban and architectural risk factors for malaria in indigenous Amazonian settlements in Brazil: a typological analysis. Malar J. 2015;14:284. Published 2015 Jul 22. doi:10.1186/s12936- 015-0806-0

Thomson-Luque R, Scopel KK. Immature reticulocytes as preferential host cells and the challenges for in vitro culture of Plasmodium vivax. Pathog Glob Health. 2015;109(3):91-92. doi:10.1179/2047772415Z.00000000026

2014

Stefanie C. P. Lopes, Letusa Albrecht, Bruna O. Carvalho, André M. Siqueira, Richard Thomson-Luque, Paulo A. Nogueira, Carmen Fernandez-Becerra, Hernando A. del Portillo, Bruce M. Russell, Laurent Rénia, Marcus V. G. Lacerda, Fabio T. M. Costa, Paucity of Plasmodium vivax Mature Schizonts in Peripheral Blood Is Associated With Their Increased Cytoadhesive Potential, The Journal of Infectious Diseases, Volume 209, Issue 9, 1 May 2014, Pages 1403–1407, https://doi.org/10.1093/infdis/jiu018

2013

Martin-Jaular L, Elizalde-Torrent A, Thomson-Luque R, Ferrer M, Segovia JC, Esperanza Herreros-Aviles, Fernández-Becerra C and del Portillo HA. Reticulocyte prone malaria parasites predominantly invade CD71hi immature cells: implications for the development of an in vitro culture for Plasmodium vivax. Malar J. 2013;12(1):434. doi:10.1186/1475-2875-12-434

Fernandez-Becerra C, Lelievre J, Ferrer M, Anton N, Thomson-Luque R, Peligero C, Almela MJ, Lacerda MV, Herreros E, del Portillo, H. A. (2013). Red blood cells derived from peripheral blood and bone marrow CD34+ human haematopoietic stem cells are permissive to Plasmodium parasites infection. Memórias Do Instituto Oswaldo Cruz, 108(6), 801–803. http://doi.org/10.1590/0074-0276108062013019

2008

Cristian Morales Indiano, Maria-Luisa Granada, Carme Biosca Adzet, Emma Ventura Orriols, Richard Thomson-Luque, August Corominas Vilardell. Estudio de la estabilidad de insulina, testosterona y péptido C en suero y de paratirina en suero y plasma. Revista del Laboratorio Clínico 1(1) SEQC (2008)

News - MCTU lab

SUM-101 Phase Ib Clinical Trial in Bagamoyo, Tanzania

This is a clinical trial for a new malaria vaccine, SumayaVac-1 (SUM-101), a collaborative effort between Sumaya Biotech GmbH & Co. KG, Swiss TPH, and the Ifakara Health Institute. The study involves healthy African adult volunteers who have been pre-exposed to malaria in Bagamoyo, Tanzania and its objectives are to assess the vaccine's safety and its ability to generate an immune response against the malaria parasite.

Forty participants split into two groups receive three doses, approximately one month apart, of either the SUM-101 vaccine or a comparator (rabies vaccine). The SUM-101 vaccine is composed of the full length merozoite surface protein (MSP-1) expressed on merozoites and during the liver stage + a potent immune-stimulatory adjuvant called GLA-SE (Glucopyranosyl Lipid A Adjuvant-Stable Emulsion). The vaccine simultaneously targets the two crucial stages of the parasite’s infectious cycle, the liver and the blood stage.

EU Malaria Fund supports Sumaya Biotech

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The EU Malaria Fund (EUMF) is a public-private partnership between the European Union, International Organizations, corporations, and organized civic society, providing a novel funding instrument to address market failures in infectious diseases with significant relevance to public health globally. On 30 September the EUMF finalized its investments into four innovative companies active in malaria R&D, among these Sumaya Biotech. In total, nine promising and innovative malaria projects, covering treatments, vaccines, and diagnostics are being supported.

The focus of Sumaya Biotech GmbH & Co. KG is on the clinical development of a novel, innovative malaria vaccine based on the full - length MSP - 1 protein. The second project of Sumaya targets the development of SC83288, an anti - malarial compound. The two projects are carried out in close cooperation with our unit.

How to get in touch:

Richard Thomson Luque

Scientific Director MCTU Lab

Centre for Infectious Diseases, Parasitology
Heidelberg University Hospital
Im Neuenheimer Feld 324
69120 Heidelberg, Germany

Tel. +49 (0)6221 56-7827 (office) / -4415 (lab) / -7438 (PhD office)

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