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2. Line shape analysis of the K$\beta$ transition in muonic hydrogen

Author

Covita, D. S., Anagnostopoulos, D. F., Fuhrmann, H., Gorke, H., Gotta, D., Gruber, A., Hirtl, A., Ishiwatari, T., Indelicato, P., Jensen, T. S., Bigot, E. -O. Le, Markushin, V. E., Nekipelov, M., Pomerantsev, V. N., Popov, V. P., Santos, J. M. F. dos, Schmid, Ph., Simons, L. M., Theisen, M., Trassinelli, M., Veloso, J. F. C. A., and Zmeskal, J.

Subjects
Physics - Atomic Physics, Nuclear Experiment
Abstract

The K$\beta$ transition in muonic hydrogen was measured with a high-resolution crystal spectrometer. The spectrum is shown to be sensitive to the ground-state hyperfine splitting, the corresponding triplet-to-singlet ratio, and the kinetic energy distribution in the $3p$ state. The hyperfine splitting and triplet-to-singlet ratio are found to be consistent with the values expected from theoretical and experimental investigations and, therefore, were fixed accordingly in order to reduce the uncertainties in the further reconstruction of the kinetic energy distribution. The presence of high-energetic components was established and quantified in both a phenomenological, i.e. cascade-model-free fit, and in a direct deconvolution of the Doppler broadening based on the Bayesian approach., Comment: 22 pages, 21 figures

Published
2017
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3. Perovskite–organic tandem solar cells with indium oxide interconnect

Author

Brinkmann, K. O., Becker, T., Zimmermann, F., Kreusel, C., Gahlmann, T., Theisen, M., Haeger, T., Olthof, S., Tückmantel, C., Günster, M., Maschwitz, T., Göbelsmann, F., Koch, C., Hertel, D., Caprioglio, P., Peña-Camargo, F., Perdigón-Toro, L., Al-Ashouri, A., Merten, L., Hinderhofer, A., Gomell, L., Zhang, S., Schreiber, F., Albrecht, S., Meerholz, K., Neher, D., Stolterfoht, M., and Riedl, T.

Published
2022
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4. A Pfs48/45-based vaccine to block Plasmodium falciparum transmission:phase 1, open-label, clinical trial

Author

Alkema, M., Smit, M. J., Marin-Mogollon, C., Totté, K., Teelen, K., van Gemert, G. J., van de Vegte-Bolmer, M., Mordmüller, B. G., Reimer, J. M., Lövgren-Bengtsson, K. L., Sauerwein, R. W., Bousema, T., Plieskatt, J., Theisen, M., Jore, M. M., McCall, M. B.B., Alkema, M., Smit, M. J., Marin-Mogollon, C., Totté, K., Teelen, K., van Gemert, G. J., van de Vegte-Bolmer, M., Mordmüller, B. G., Reimer, J. M., Lövgren-Bengtsson, K. L., Sauerwein, R. W., Bousema, T., Plieskatt, J., Theisen, M., Jore, M. M., and McCall, M. B.B.

Abstract

Background: The stalling global progress in malaria control highlights the need for novel tools for malaria elimination, including transmission-blocking vaccines. Transmission-blocking vaccines aim to induce human antibodies that block parasite development in the mosquito and mosquitoes becoming infectious. The Pfs48/45 protein is a leading Plasmodium falciparum transmission-blocking vaccine candidate. The R0.6C fusion protein, consisting of Pfs48/45 domain 3 (6C) and the N-terminal region of P. falciparum glutamate-rich protein (R0), has previously been produced in Lactococcus lactis and elicited functional antibodies in rodents. Here, we assess the safety and transmission-reducing efficacy of R0.6C adsorbed to aluminium hydroxide with and without Matrix-M™ adjuvant in humans. Methods: In this first-in-human, open-label clinical trial, malaria-naïve adults, aged 18–55 years, were recruited at the Radboudumc in Nijmegen, the Netherlands. Participants received four intramuscular vaccinations on days 0, 28, 56 and 168 with either 30 µg or 100 µg of R0.6C and were randomised for the allocation of one of the two different adjuvant combinations: aluminium hydroxide alone, or aluminium hydroxide combined with Matrix-M1™ adjuvant. Adverse events were recorded from inclusion until 84 days after the fourth vaccination. Anti-R0.6C and anti-6C IgG titres were measured by enzyme-linked immunosorbent assay. Transmission-reducing activity of participants’ serum and purified vaccine-specific immunoglobulin G was assessed by standard membrane feeding assays using laboratory-reared Anopheles stephensi mosquitoes and cultured P. falciparum gametocytes. Results: Thirty-one participants completed four vaccinations and were included in the analysis. Administration of all doses was safe and well-tolerated, with one related grade 3 adverse event (transient fever) and no serious adverse events occurring. Anti-R0.6C and anti-6C IgG titres were similar between the 30 and 100 µg R0.6C arms

Published
2024

5. Associations between Antibodies to a Panel of Plasmodium falciparum Specific Antigens and Response to Sub-Optimal Antimalarial Therapy in Kampala, Uganda

Author

Rosenthal, Philip, Greenhouse, Bryan, Dorsey, Matthew, Keh, CE, Jha, AR, Nzarubara, B, Lanar, DE, Dutta, S, Theisen, M, Rosenthal, PJ, Dorsey, G, and Nixon, DF

Abstract

Background: Antibodies are important in the control of blood stage Plasmodium falciparum infection. It is unclear which antibody responses are responsible for, or even associated with protection, partly due to confounding by heterogeneous exposure. Assessm

Published
2012

6. Pionic hydrogen and deuterium

Author

Gotta D., Amaro F.D., Anagnostopoulos D.F., Bühler P., Covita D.S., Fuhrmann H., Gorke H., Gruber A., Hennebach M., Hirtl A., Ishiwatari T., Indelicato P., Jensen T.S., Le Bigot E.-O., Liu Y.-W., Manil B., Markushin V.E., Marton J., Nekipelov M., Pomerantsev V.N., Popov V.P., el Hassani A. J. Rusi, dos Santos J. M. F., Schlesser S., Schmid Ph., Simons L.M., Strauch Th., Theisen M., Trassinelli M., Veloso J. F. C. A., and Zmeskal J.

Subjects
Physics, QC1-999
Abstract

The strong-interaction effects both in pionic hydrogen and deuterium atoms have been re-determined with improved precision. The hadronic shift and width in pionic hydrogen together with the hadronic shift in pionic deuterium constitute a one-fold constraint for the two independent pion-nucleon scattering lengths. Furthermore, the hadronic width in pionic deuterium measures the transition strength of s-wave pions on an isoscalar nucleon-nucleon pair which is an independent quantity not related to the pion-nucleon scattering lengths. The experiment was performed at the Paul Scherrer Institute by stopping a high-intensity low-energy pion beam in gaseous targets using the cyclotron trap. The X-rays emitted by the πH and πD atoms were analysed with a high resolution Bragg spectrometer equipped with spherically bent crystals. The pion-nucleon scattering lengths and other physical quantities extracted from the atom data are in good agreement with the results obtained from pionnucleon and nucleon-nucleon scattering experiments and confirm that a consistent picture is achieved for the low-energy pion-nucleon sector with respect to the expectations of chiral perturbation theory.

Published
2022
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8. Anti-gametocyte antigen humoral immunity and gametocytemia during treatment of uncomplicated falciparum malaria: a multi-national study

Author

O'Flaherty, K, Chan, J-A, Cutts, JC, Zaloumis, SG, Ashley, EA, Phyo, AP, Drew, DR, Dondorp, AM, Day, NP, Dhorda, M, Fairhurst, RM, Lim, P, Amaratunga, C, Pukrittayakamee, S, Hien, TT, Htut, Y, Mayxay, M, Faiz, MA, Mokuolu, OA, Onyamboko, MA, Fanello, C, Takashima, E, Tsuboi, T, Theisen, M, Nosten, F, Beeson, JG, Simpson, JA, White, NJ, Fowkes, FJI, and Intensive Care Medicine

Subjects
Microbiology (medical), Immunology, Malaria, Falciparum/drug therapy, Plasmodium falciparum, Antibodies, Protozoan, Antigens, Protozoan, Microbiology, immunity, Immunity, Humoral, Malaria, Infectious Diseases, epidemiogy, Seroepidemiologic Studies, gametocyte, Immunoglobulin G, antibodies, falciparum malaria, Humans, clinical malaria, Malaria, Falciparum
Abstract

IntroductionUnderstanding the human immune response to Plasmodium falciparum gametocytes and its association with gametocytemia is essential for understanding the transmission of malaria as well as progressing transmission blocking vaccine candidates.MethodsIn a multi-national clinical efficacy trial of artemisinin therapies (13 sites of varying transmission over South-East Asia and Africa), we measured Immunoglobulin G (IgG) responses to recombinant P. falciparum gametocyte antigens expressed on the gametocyte plasma membrane and leading transmission blocking vaccine candidates Pfs230 (Pfs230c and Pfs230D1M) and Pfs48/45 at enrolment in 1,114 participants with clinical falciparum malaria. Mixed effects linear and logistic regression were used to determine the association between gametocyte measures (gametocytemia and gametocyte density) and antibody outcomes at enrolment.ResultsMicroscopy detectable gametocytemia was observed in 11% (127/1,114) of participants at enrolment, and an additional 9% (95/1,114) over the follow-up period (up to day 42) (total 20% of participants [222/1,114]). IgG levels in response to Pfs230c, Pfs48/45 and Pfs230D1M varied across study sites at enrolment (p < 0.001), as did IgG seroprevalence for anti-Pfs230c and D1M IgG (p < 0.001), but not for anti-Pfs48/45 IgG (p = 0.159). In adjusted analyses, microscopy detectable gametocytemia at enrolment was associated with an increase in the odds of IgG seropositivity to the three gametocyte antigens (Pfs230c OR [95% CI], p: 1.70 [1.10, 2.62], 0.017; Pfs48/45: 1.45 [0.85, 2.46], 0.174; Pfs230D1M: 1.70 [1.03, 2.80], 0.037), as was higher gametocyte density at enrolment (per two-fold change in gametocyte density Pfs230c OR [95% CI], p: 1.09 [1.02, 1.17], 0.008; Pfs48/45: 1.05 [0.98, 1.13], 0.185; Pfs230D1M: 1.07 [0.99, 1.14], 0.071).ConclusionPfs230 and Pfs48/45 antibodies are naturally immunogenic targets associated with patent gametocytemia and increasing gametocyte density across multiple malaria endemic settings, including regions with emerging artemisinin-resistant P. falciparum.

Published
2022
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10. Pionic hydrogen and friends

Author

Gotta, D., Amaro, F. D., Anagnostopoulos, D. F., Bühler, P., Gorke, H., Covita, D. S., Fuhrmann, H., Gruber, A., Hennebach, M., Hirtl, A., Ishiwatari, T., Indelicato, P., Jensen, T. S., Bigot, E.-O. Le, Markushin, V. E., Marton, J., Nekipelov, M., Pomerantsev, V. N., Popov, V. P., dos Santos, J. M. F., Schlesser, S., Schmid, Ph., Simons, L. M., Strauch, Th., Theisen, M., Trassinelli, M., Veloso, J. F. C. A., and Zmeskal, J.

Published
2015
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30. Plasmodium falciparum merozoite surface antigen-specific cytophilic IgG and control of malaria infection in a Beninese birth cohort

Author

Adamou, R., Dechavanne, Célia, Sadissou, I., D'Almeida, T., Bouraima, A., Sonon, P., Amoussa, R., Cottrel, Gilles, Le Port, A., Theisen, M., Remarque, E.J., Longacre, S., Moutairou, K., Massougbodji, A., Luty, Adrian, Nuel, G., Migot Nabias, Florence, Sanni, A., Garcia, André, and Milet, Jacqueline

Subjects
ANTIGENE, parasitic diseases, ENFANT D'AGE PRESCOLAIRE, VACCINATION, FACTEUR DE RISQUE, PALUDISME, NOURRISSON, IMMUNOLOGIE, PARASITE, MILIEU RURAL, ANTICORPS
Abstract

Background : Substantial evidence indicates that cytophilic IgG responses to Plasmodiumfalciparum merozoite antigens play a role in protection from malaria. The specific targets mediating immunity remain unclear. Evaluating antibody responses in infants naturally-exposed to malaria will allow to better understand the establishment of anti-malarial immunity and to contribute to a vaccine development by identifying the most appropriate merozoite candidate antigens. Methods : The study was based on parasitological and clinical active follow-up of infants from birth to 18months of age conducted in the Tori Bossito area of southern Benin. For 399 infants, plasma levels of cytophilic IgG antibodies with specificity for five asexual stage malaria vaccine candidate antigens were determined by ELISA in infants' peripheral blood at 6, 9, 12 and 15months of age. Multivariate mixed logistic model was used to investigate the association between antibody levels and anti-malarial protection in the trimester following the IgG quantification. Moreover, the concentrations of merozoite antigen-specific IgG were compared between a group of infants apparently able to control asymptomatic malaria infection (CAIG) and a group of infants with no control of malaria infection (Control group (NCIG)). Protective effect of antibodies was also assessed after 15months of malaria exposure with a Cox regression model adjusted on environmental risk. Results : Cytophilic IgG responses to AMA1, MSP1, MSP2-3D7, MSP2-FC27, MSP3 and GLURP R2 were associated with increasing malarial infection risk in univariate analysis. The multivariate mixed model showed that IgG1 and IgG3 to AMA1 were associated with an increased risk of malarial infection. However infants from CAIG (n=53) had significantly higher AMA1-, MSP2-FC27-, MSP3-specific IgG1 and AMA1-, MSP1-, MSP2-FC27-, MSP3 and GLURP-R2-specific IgG3 than those from NCIG (n=183). The latter IgG responses were not associated with protection against clinical malaria in the whole cohort when protective effect is assessed after 15months of malaria exposition. Conclusion : In this cohort, merozoite antigen-specific cytophilic IgG levels represent a marker of malaria exposure in infants from 6 to 18 months of age. However, infants with resolution of asymptomatic infection (CAIG) seem to have acquired naturally immunity against P. falciparum. This observation is encouraging in the context of the development of multitarget P. falciparum vaccines.

Published
2019

31. Unravelling the immune signature of Plasmodium falciparum transmission-reducing immunity (vol 9, 558, 2018)

Author

Stone, W.J.R., Campo, J.J., Ouedraogo, A.L., Meerstein-Kessel, L., Morlais, I., D. da, Cohuet, A., Nsango, S., Sutherland, C.J., Vegte-Bolmer, M.V. van de, Siebelink-Stoter, R., Gemert, G.J. van, Graumans, W., Lanke, K., Shandling, A.D., Pablo, J.V., Teng, A.A., Jones, S., Jong, R.M. de, Fabra-Garcia, A., Bradley, J., Roeffen, W., Lasonder, E., Gremo, G., Schwarzer, E., Janse, C.J., Singh, S.K., Theisen, M., Felgner, P., Marti, M., Drakeley, C., Sauerwein, R., Bousema, T., and Jore, M.M.

Published
2018
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39. Warum haben Kinder relativ selten Gallensteine? : Untersuchungen der Lithoindices und des Gallensäurenmusters bei gesunden sowie kranken Säuglingen und Kindern

Author

Niessen, K. H., Theisen, M., Bachmann, K. D., editor, Berger, H., editor, Bierich, J., editor, Boda, D., editor, Bremer, H.-J., editor, Brodehl, J., editor, Burgio, G. R., editor, Fischer, K., editor, Gladtke, E., editor, Hadorn, B., editor, Hagberg, B., editor, Hallman, N., editor, Hansen, H. G., editor, Harbauer, H., editor, von Harnack, G.-A., editor, Hecker, W. C., editor, Helge, H., editor, Hitzig, W. H., editor, Huth, E., editor, Kleihauer, E., editor, Künzer, W., editor, Lassrich, M. A., editor, Leiber, B., editor, Lindquist, B., editor, Marget, W., editor, Oehme, J., editor, Olbing, H., editor, Pfeiffer, R. A., editor, Prader, A., editor, Riegel, K., editor, Rossi, E., editor, Schärer, K., editor, Schmidt, E., editor, Schulte, F.-J., editor, Spiess, H., editor, Spranger, J., editor, Stalder, G., editor, Stephan, U., editor, Stoermer, J., editor, Ströder, J., editor, Teller, W., editor, Zetterström, R., editor, and Zweymüller, E., editor

Published
1980
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40. A phase 2b randomized, controlled trial of the efficacy of the GMZ2 malaria vaccine in African children

Author

Sirima, SB, Mordmüller, B, Milligan, P, Ngoa, UA, Kironde, F, Atuguba, F, Tiono, AB, Issifou, S, Kaddumukasa, M, Bangre, O, Flach, C, Christiansen, M, Bang, P, Chilengi, R, Jepsen, S, Kremsner, PG, Theisen, M, GMZ2 Trial Study Group, COLLABORATORS, Ouédraogo, A, Kargougou, D, Nébié, I, Débé, S, Diarra, A, Bougouma, E, Hounkpatin, AB, Adegnika, AA, Lell, B, Joanny, F, Honkpehedji, YJ, Agobe, JC, Esen, M, Ajua, A, Asoala, V, Anyorigiya, T, Ansah, NA, Buwembo, W, Mworozi, E, Sekikubo, M, Abubakar, I, Bojang, K, Noor, R, Okech, B, and Ejigu, DA

Subjects
parasitic diseases
Abstract

GMZ2 is a recombinant protein malaria vaccine, comprising two blood-stage antigens of Plasmodium falciparum, glutamate-rich protein and merozoite surface protein 3. We assessed efficacy of GMZ2 in children in Burkina Faso, Gabon, Ghana and Uganda. : Children 12-60months old were randomized to receive three injections of either 100μg GMZ2 adjuvanted with aluminum hydroxide or a control vaccine (rabies) four weeks apart and were followed up for six months to measure the incidence of malaria defined as fever or history of fever and a parasite density ⩾5000/μL. : A cohort of 1849 children were randomized, 1735 received three doses of vaccine (868 GMZ2, 867 control-vaccine). There were 641 malaria episodes in the GMZ2/Alum group and 720 in the control group. In the ATP analysis, vaccine efficacy (VE), adjusted for age and site was 14% (95% confidence interval [CI]: 3.6%, 23%, p-value=0.009). In the ITT analysis, age-adjusted VE was 11.3% (95% CI 2.5%, 19%, p-value=0.013). VE was higher in older children. In GMZ2-vaccinated children, the incidence of malaria decreased with increasing vaccine-induced anti-GMZ2 IgG concentration. There were 32 cases of severe malaria (18 in the rabies vaccine group and 14 in the GMZ2 group), VE 27% (95% CI -44%, 63%). : GMZ2 is the first blood-stage malaria vaccine to be evaluated in a large multicenter trial. GMZ2 was well tolerated and immunogenic, and reduced the incidence of malaria, but efficacy would need to be substantially improved, using a more immunogenic formulation, for the vaccine to have a public health role.

Published
2016

43. Expression, Purification and Characterization of GMZ2'.10C, a Complex Disulphide-Bonded Fusion Protein Vaccine Candidate against the Asexual and Sexual Life-Stages of the Malaria-Causing Plasmodium falciparum Parasite

Author

Mistarz, U.H., Singh, S.K, Nguyen, T., Roeffen, W., Lissau, C., Madsen, S.M., Vrang, A., Tiendrebeogo, R.W., Kana, I.H., Sauerwein, R.W., Theisen, M., Rand, K.D., Mistarz, U.H., Singh, S.K, Nguyen, T., Roeffen, W., Lissau, C., Madsen, S.M., Vrang, A., Tiendrebeogo, R.W., Kana, I.H., Sauerwein, R.W., Theisen, M., and Rand, K.D.

Abstract

Contains fulltext : 177586.pdf (publisher's version ) (Closed access), PURPOSE: Production and characterization of a chimeric fusion protein (GMZ2'.10C) which combines epitopes of key malaria parasite antigens: glutamate-rich protein (GLURP), merozoite surface protein 3 (MSP3), and the highly disulphide bonded Pfs48/45 (10C). GMZ2'.10C is a potential candidate for a multi-stage malaria vaccine that targets both transmission and asexual life-cycle stages of the parasite. METHODS: GMZ2'.10C was produced in Lactococcus lactis and purified using either an immunoaffinity purification (IP) or a conventional purification (CP) method. Protein purity and stability was analysed by RP-HPLC, SEC-HPLC, 2-site ELISA, gel-electrophoresis and Western blotting. Structural characterization (mass analysis, peptide mapping and cysteine connectivity mapping) was performed by LC-MS/MS. RESULTS: CP-GMZ2'.10C resulted in similar purity, yield, structure and stability as compared to IP-GMZ2'.10C. CP-GMZ2'.10C and IP-GMZ2'.10C both elicited a high titer of transmission blocking (TB) antibodies in rodents. The intricate disulphide-bond connectivity of C-terminus Pfs48/45 was analysed by tandem mass spectrometry and was established for GMZ2'.10C and two reference fusion proteins encompassing similar parts of Pfs48/45. CONCLUSION: GMZ2'.10C, combining GMZ2' and correctly-folded Pfs48/45 can be produced by the Lactoccus lactis P170 based expression system in purity and quality for pharmaceutical development and elicit high level of TB antibodies. The cysteine connectivity for the 10C region of Pfs48/45 was revealed experimentally, providing an important guideline for employing the Pfs48/45 antigen in vaccine design.

Published
2017

44. Construct design, production, and characterization of Plasmodium falciparum 48/45 R0.6C subunit protein produced in Lactococcus lactis as candidate vaccine

Author

Singh, S.K, Roeffen, W., Mistarz, U.H., Chourasia, B.K., Yang, F., Rand, K.D., Sauerwein, R.W., Theisen, M., Singh, S.K, Roeffen, W., Mistarz, U.H., Chourasia, B.K., Yang, F., Rand, K.D., Sauerwein, R.W., and Theisen, M.

Abstract

Contains fulltext : 177563.pdf (publisher's version ) (Open Access), BACKGROUND: The sexual stages of Plasmodium falciparum are responsible for the spread of the parasite in malaria endemic areas. The cysteine-rich Pfs48/45 protein, exposed on the surface of sexual stages, is one of the most advanced antigens for inclusion into a vaccine that will block transmission. However, clinical Pfs48/45 sub-unit vaccine development has been hampered by the inability to produce high yields of recombinant protein as the native structure is required for the induction of functional transmission-blocking (TB) antibodies. We have investigated a downstream purification process of a sub-unit (R0.6C) fragment representing the C-terminal 6-Cys domain of Pfs48/45 (6C) genetically fused to the R0 region (R0) of asexual stage Glutamate Rich Protein expressed in Lactococcus lactis. RESULTS: A series of R0.6C fusion proteins containing features, which aim to increase expression levels or to facilitate protein purification, were evaluated at small scale. None of these modifications affected the overall yield of recombinant protein. Consequently, R0.6C with a C-terminal his tag was used for upstream and downstream process development. A simple work-flow was developed consisting of batch fermentation followed by two purification steps. As such, the recombinant protein was purified to homogeneity. The composition of the final product was verified by HPLC, mass spectrometry, SDS-PAGE and Western blotting with conformation dependent antibodies against Pfs48/45. The recombinant protein induced high levels of functional TB antibodies in rats. CONCLUSIONS: The established production and purification process of the R0.6C fusion protein provide a strong basis for further clinical development of this candidate transmission blocking malaria vaccine.

Published
2017

45. Towards clinical development of a Pfs48/45-based transmission blocking malaria vaccine

Author

Theisen, M., Jore, M.M., Sauerwein, R.W., Theisen, M., Jore, M.M., and Sauerwein, R.W.

Abstract

Contains fulltext : 170299.pdf (publisher's version ) (Closed access), INTRODUCTION: Malaria is a devastating vector-borne disease caused by the Plasmodium parasite, resulting in almost 0.5 million casualties per year. The parasite has a complex life-cycle that includes asexual replication in human red blood cells, causing symptomatic malaria, and sexual stages which are essential for the transmission to the mosquito vector. A vaccine targeting the sexual stages of the parasite and thus blocking transmission will be instrumental for the eradication of malaria. One of the leading transmission blocking vaccine candidates is the sexual stage antigen Pfs48/45. Areas covered: PubMed was searched to review the progress and future prospects for clinical development of a Pfs48/45-based subunit vaccine. We will focus on biological function, naturally acquired immunity, functional activity of specific antibodies, sequence diversity, production of recombinant protein and preclinical studies. Expert commentary: Pfs48/45 is one of the lead-candidates for a transmission blocking vaccine and should be further explored in clinical trials.

Published
2017

46. Abstracts of the Eighth EDCTP Forum, 6-9 November 2016.

Author

Makanga, M, Beattie, P, Breugelmans, G, Nyirenda, T, Bockarie, M, Tanner, M, Volmink, J, Hankins, C, Walzl, G, Chegou, N, Malherbe, S, Hatherill, M, Scriba, TJ, Zak, DE, Barry, CE, Kaufmann, SHE, Noor, A, Strub-Wourgaft, N, Phillips, P, Munguambe, K, Ravinetto, R, Tinto, H, Diro, E, Mahendrahata, Y, Okebe, J, Rijal, S, Garcia, C, Sundar, S, Ndayisaba, G, Sopheak, T, Ngoduc, T, Van Loen, H, Jacobs, J, D'Alessandro, U, Boelaert, M, Buvé, A, Kamalo, P, Manda-Taylor, L, Rennie, S, Mokgatla, B, Bahati, Ijsselmuiden, C, Afolabi, M, Mcgrath, N, Kampmann, B, Imoukhuede, E, Alexander, N, Larson, H, Chandramohan, D, Bojang, K, Kasaro, MP, Muluka, B, Kaunda, K, Morse, J, Westfall, A, Kapata, N, Kruuner, A, Henostroza, G, Reid, S, Alabi, A, Foguim, F, Sankarganesh, J, Bruske, E, Mfoumbi, A, Mevyann, C, Adegnika, A, Lell, B, Kranzer, K, Kremsner, P, Grobusch, M, Sabiiti, W, Ntinginya, N, Kuchaka, D, Azam, K, Kampira, E, Mtafya, B, Bowness, R, Bhatt, N, Davies, G, Kibiki, G, Gillespie, S, Lejon, V, Ilboudo, H, Mumba, D, Camara, M, Kaba, D, Lumbala, C, Fèvre, E, Jamonneau, V, Bucheton, B, Büscher, P, Chisenga, C, Sinkala, E, Chilengi, R, Chitundu, H, Zyambo, Z, Wandeler, G, Vinikoor, M, Emilie, D, Camara, O, Mathurin, K, Guiguigbaza-Kossigan, D, Philippe, B, Regassa, F, Hassane, S, Bienvenu, SM, Fabrice, C, Ouédraogo, E, Kouakou, L, Owusu, M, Mensah, E, Enimil, A, Mutocheluh, M, Ndongo, FA, Tejiokem, MC, Texier, G, Penda, C, Ndiang, S, Ndongo, J-A, Guemkam, G, Sofeu, CL, Afumbom, K, Faye, A, Msellati, P, Warszawski, J, Vos, A, Devillé, W, Barth, R, Klipstein-Grobusch, K, Tempelman, H, Venter, F, Coutinho, R, Grobbee, D, Ssemwanga, D, Lyagoba, F, Magambo, B, Kapaata, A, Kirangwa, J, Nannyonjo, M, Nassolo, F, Nsubuga, R, Yebra, G, Brown, A, Kaleebu, P, Nylén, H, Habtewold, A, Makonnen, E, Yimer, G, Burhenne, J, Diczfalusy, U, Aklillu, E, Steele, D, Walker, R, Simuyandi, M, Beres, L, Bosomprah, S, Ansumana, R, Taitt, C, Lamin, JM, Jacobsen, KH, Mulvaney, SP, Leski, T, Bangura, U, 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J-P, Sissoko, S, Sangaré, C, Toure, S, Sanogo, K, Diakite, H, Doumbia, D, Haidara, K, Julé, A, Ashurst, H, Merson, L, Olliaro, P, Marsh, V, Lang, T, Guérin, P, Awuondo, K, Njenga, D, Nyakarungu, E, Titus, P, Sutamihardja, A, Lowe, B, Ogutu, B, Billingsley, P, Soulama, I, Kaboré, M, Coulibaly, A, Ouattara, M, Sanon, S, Diarra, A, Bougouma, E, Ouedraogo, A, Sombie, B, Kargougou, D, Ouattara, D, Issa, N, Tiono, A, Sirima, S, Chaponda, M, Dabira, E, Dao, F, Dara, N, Coulibaly, M, Tolo, A, Maiga, H, Ouologuem, N, Niangaly, H, Botchway, F, Wilson, N, Dickinson-Copeland, CM, Adjei, AA, Wilson, M, Stiles, JK, Hamid, MA, Awad-Elgeid, M, Nasr, A, Netongo, P, Kamdem, S, Velavan, T, Lasry, E, Diarra, M, Bamadio, A, Traore, A, Coumare, S, Soma, B, Dicko, Y, Sangare, B, Tembely, A, Traore, D, Haidara, A, Dicko, A, Diawara, E, Beavogui, A, Camara, D, Sylla, M, Yattara, M, Sow, A, Camara, GC, Diallo, S, Mombo-Ngoma, G, Remppis, J, Sievers, M, Manego, RZ, Endamne, L, Hutchinson, D, Held, J, Supan, C, Salazar, CLO, Bonkian, LN, Nahum, A, Sié, A, Abdulla, S, Cantalloube, C, Djeriou, E, Bouyou-Akotet, M, Mordmüller, B, Siribie, M, Sirima, SB, Ouattara, SM, Coulibaly, S, Kabore, JM, Amidou, D, Tekete, M, Traore, O, Haefeli, W, Borrmann, S, Kaboré, N, Kabré, Z, Nikèma, F, Compaoré, D, Somé, F, Djimdé, A, Ouédraogo, J, Chalwe, V, Miller, J, Diakité, H, Greco, B, Spangenberg, T, Kourany-Lefoll, E, Oeuvray, C, Mulry, J, Tyagarajan, K, Magsaam, B, Barnes, K, Hodel, EM, Humphreys, G, Pace, C, Banda, CG, Denti, P, Allen, E, Lalloo, D, Mwapasa, V, Terlouw, A, Mwesigwa, J, Achan, J, Jawara, M, Ditanna, G, Worwui, A, Affara, M, Koukouikila-Koussounda, F, Kombo, M, Vouvoungui, C, Ntoumi, F, Etoka-Beka, MK, Deibert, J, Poulain, P, Kobawila, S, Gueye, NG, Seda, B, Kwambai, T, Jangu, P, Samuels, A, Kuile, FT, Kariuki, S, Barry, A, Bousema, T, Okech, B, Egwang, T, Corran, P, Riley, E, Ezennia, I, Ekwunife, O, Muleba, M, Stevenson, J, Mbata, K, Coetzee, M, Norris, D, Moneke-Anyanwoke, N, Momodou, J, Clarke, E, Scott, S, Tijani, A, Djimde, M, Vaillant, M, Samouda, H, Mensah, V, Roetynck, S, Kanteh, E, Bowyer, G, Ndaw, A, Oko, F, Bliss, C, Jagne, YJ, Cortese, R, Nicosia, A, Roberts, R, D'Alessio, F, Leroy, O, Faye, B, Cisse, B, Gerry, S, Viebig, N, Lawrie, A, Ewer, K, Hill, A, Nebie, I, Tiono, AB, Sanou, G, Konate, AT, Yaro, BJ, Sodiomon, S, Honkpehedji, Y, Agobe, JCD, Zinsou, F, Mengue, J, Richie, T, Hoffman, S, Nouatin, O, Ngoa, UA, Edoa, JR, Homoet, A, Engelhon, JE, Massinga-Louembe, M, Esen, M, Theisen, M, Sim, KL, Luty, AJ, Moutairou, K, Dinko, B, King, E, Targett, G, Sutherland, C, Likhovole, C, Ouma, C, Vulule, J, Musau, S, Khayumbi, J, Okumu, A, Murithi, W, Otu, J, Gehre, F, Zingue, D, Kudzawu, S, Forson, A, Mane, M, Rabna, P, Diarra, B, Kayede, S, Adebiyi, E, Kehinde, A, Onyejepu, N, Onubogu, C, Idigbe, E, Ba, A, Diallo, A, Mboup, S, Disse, K, Kadanga, G, Dagnra, Y, Baldeh, I, Corrah, T, De Jong, B, Antonio, M, Musanabaganwa, C, Musabyimana, JP, Karita, E, Diop, B, Nambajimana, A, Dushimiyimana, V, Karame, P, Russell, J, Ndoli, J, Hategekimana, T, Sendegeya, A, Condo, J, Binagwaho, A, Okonko, I, Okerentugba, P, Opaleye, O, Awujo, E, Frank-Peterside, N, Moyo, S, Kotokwe, K, Mohammed, T, Boleo, C, Mupfumi, L, Chishala, S, Gaseitsiwe, S, Tsalaile, L, Bussmann, H, Makhema, J, Baum, M, Marlink, R, Engelbretch, S, Essex, M, Novitsky, V, Saka, E, Kalipalire, Z, Bhairavabhotla, R, Midiani, D, Sherman, J, Mgode, G, Cox, C, Bwana, D, Mtui, L, Magesa, D, Kahwa, A, Mfinanga, G, Mulder, C, Borain, N, Petersen, L, Du Plessis, J, Theron, G, Holm-Hansen, C, Tekwu, EM, Sidze, LK, Assam, JPA, Eyangoh, S, Niemann, S, Beng, VP, Frank, M, Atiadeve, S, Hilmann, D, Awoniyi, D, Baumann, R, Kriel, B, Jacobs, R, Kidd, M, Loxton, A, Kaempfer, S, Singh, M, Mwanza, W, Milimo, D, Moyo, M, Kasese, N, Cheeba-Lengwe, M, Munkondya, S, Ayles, H, De Haas, P, Muyoyeta, M, Namuganga, AR, Kizza, HM, Mendy, A, Tientcheu, L, Ayorinde, A, Coker, E, Egere, U, Coussens, A, Naude, C, Chaplin, G, Noursadeghi, M, Martineau, A, Jablonski, N, Wilkinson, R, Ouedraogo, HG, Matteelli, A, Regazzi, M, Tarnagda, G, Villani, P, Sulis, G, Diagbouga, S, Roggi, A, Giorgetti, F, Kouanda, S, Bidias, A, Ndjonka, D, Olemba, C, Souleymanou, A, Mukonzo, J, Kuteesa, R, Ogwal-Okeng, J, Gustafsson, LL, Owen, J, Bassi, P, Gashau, W, Olaf, K, Dodoo, A, Okonkwo, P, Kanki, P, Maruapula, D, Seraise, B, Einkauf, K, Reilly, A, Rowley, C, Musonda, R, Framhein, A, Mpagama, S, Semvua, H, Maboko, L, Hoelscher, M, Heinrich, N, Mulenga, L, Kaayunga, C, Davies, M-A, Egger, M, Musukuma, K, Dambe, R, Usadi, B, Ngari, M, Thitiri, J, Mwalekwa, L, Fegan, G, Berkley, J, Nsagha, D, Munamunungu, V, Bolton, C, Siyunda, A, Shilimi, J, Bucciardini, R, Fragola, V, Abegaz, T, Lucattini, S, Halifom, A, Tadesse, E, Berhe, M, Pugliese, K, De Castro, P, Terlizzi, R, Fucili, L, Di Gregorio, M, Mirra, M, Zegeye, T, Binelli, A, Vella, S, Abraham, L, Godefay, H, Rakotoarivelo, R, Raberahona, M, Randriamampionona, N, Andriamihaja, R, Rasamoelina, T, Cornet, M, De Dieu Randria, MJ, Benet, T, Vanhems, P, Andrianarivelo, MR, Chirwa, U, Michelo, C, Hamoonga, R, Wandiga, S, Oduor, P, Agaya, J, Sharma, A, Cavanaugh, S, Cain, K, Mukisa, J, Mupere, E, Worodria, W, Ngom, JT, Koro, F, Godwe, C, Adande, C, Ateugieu, R, Onana, T, Ngono, A, Kamdem, Y, Ngo-Niobe, S, Etoa, F-X, Kanengoni, M, Ruzario, S, Ndebele, P, Shana, M, Tarumbiswa, F, Musesengwa, R, Gutsire, R, Fisher, K, Thyagarajan, B, Akanbi, O, Binuyo, M, Ssengooba, W, Respeito, D, Mambuque, E, Blanco, S, Mandomando, I, Cobelens, F, Garcia-Basteiro, A, Tamene, A, Topp, S, Mwamba, C, Padian, N, Sikazwe, I, Geng, E, Holmes, C, Sikombe, K, Hantuba, Czaicki, N, Simbeza, S, Somwe, P, Umulisa, M, Ilo, J, Kestelyn, E, Uwineza, M, Agaba, S, Delvaux, T, Wijgert, J, Gethi, D, Odeny, L, Tamandjou, C, Kaindjee-Tjituka, F, Brandt, L, Cotton, M, Nel, E, Preiser, W, Andersson, M, Adepoju, A, Magana, M, Etsetowaghan, A, Chilikwazi, M, Sutcliffe, C, Thuma, P, Sinywimaanzi, K, Matakala, H, Munachoonga, P, Moss, W, Masenza, IS, Geisenberger, O, Agrea, P, Rwegoshora, F, Mahiga, H, Olomi, W, Kroidl, A, Kayode, G, Amoakoh-Coleman, M, Ansah, E, Uthman, O, Fokam, J, Santoro, M-M, Musolo, C, Chimbiri, I, Chikwenga, G, Deula, R, Massari, R, Lungu, A, Perno, C-F, Ndzengue, G, Loveline, N, Lissom, A, Flaurent, T, Sosso, S, Essomba, C, Kpeli, G, Otchere, I, Lamelas, A, Buultjens, A, Bulach, D, Baines, S, Seemann, T, Giulieri, S, Nakobu, Z, Aboagye, S, Owusu-Mireku, E, Danso, E, Hauser, J, Hinic, V, Pluschke, G, Stinear, T, Yeboah-Manu, D, Elshayeb, A, Siddig, ME, Ahmed, AA, Hussien, AE, Kabwe, M, Tembo, J, Chilukutu, L, Chilufya, M, Ngulube, F, Lukwesa, C, Enne, V, Wexner, H, Mwananyanda, L, Hamer, D, Sinyangwe, S, Ahmed, Y, Klein, N, Maeurer, M, Zumla, A, Bates, M, Beyala, L, Etienne, G, Anthony, N, Benjamin, A, Ateudjieu, J, Chibwe, B, Ojok, D, Tarr, CA, Perez, GM, Omeonga, S, Kibungu, F, Meyer, A, Lansana, P, Mayor, A, Onyango, P, Van Loggerenberg, F, Furtado, T, Boggs, L, Segrt, A, Dochez, C, Burnett, R, Mphahlele, MJ, Miiro, G, Mbidde, E, Peshu, N, Kivaya, E, Ngowi, B, Kavishe, R, Maowia, M, Sandstrom, E, Ayuo, E, Mmbaga, B, Leisegang, C, Thorpe, M, Batchilly, E, N'Guessan, J-P, Kanteh, D, Søfteland, S, Sebitloane, M, Vwalika, B, Taylor, M, Galappaththi-Arachchige, H, Holmen, S, Gundersen, SG, Ndhlovu, P, Kjetland, EF, Kombe, F, Toohey, J, Pienaar, E, Kredo, T, Cham, PM, Abubakar, I, Dondeh, BL, Vischer, N, Pfeiffer, C, Burri, C, Musukwa, K, Zürcher, S, Mwandu, T, Bauer, S, Adriko, M, Mwaura, P, Omolloh, K, Jones, C, Malecela, M, Hamidu, BA, Jenner, TE, Asiedu, LJ, Osei-Atweneboana, M, Afeke, I, Addo, P, Newman, M, Durnez, L, Eddyani, M, Ammisah, N, Abas, M, Quartey, M, Ablordey, A, Akinwale, O, Adeneye, A, Ezeugwu, S, Olukosi, Y, Adewale, B, Sulyman, M, Mafe, M, Okwuzu, J, Gyang, P, Nwafor, T, Henry, U, Musa, B, Ujah, I, Agobé, JCD, Grau-Pujol, B, Sacoor, C, Nhabomba, A, Casellas, A, Quintó, L, Subirà, C, Giné, R, Valentín, A, Muñoz, J, Nikiema, M, Ky-Ba, A, Comapore, KAM, Sangare, L, Oluremi, A, Michel, M, Camara, Y, Sanneh, B, Cuamba, I, Gutiérrez, J, Lázaro, C, Mejia, R, Adedeji, A, Folorunsho, S, Demehin, P, Akinsanya, B, Cowley, G, Da Silva, ET, Nabicassa, M, De Barros, PDP, Blif, MM, Bailey, R, Last, A, Mahendradhata, Y, Gotuzzo, E, De Nys, K, Casteels, M, Nona, SK, Lumeka, K, Todagbe, A, Djima, MM, Ukpong, M, Sagay, A, Khamofu, H, Torpey, K, Afiadigwe, E, Anenih, J, Ezechi, O, Nweneka, C, Idoko, J, Muhumuza, S, Katahoire, A, Nuwaha, F, Olsen, A, Okeyo, S, Omollo, R, Kimutai, R, Ochieng, M, Egondi, T, Moonga, C, Chileshe, C, Magwende, G, Anumudu, C, Onile, O, Oladele, V, Adebayo, A, Awobode, H, Oyeyemi, O, Odaibo, A, Kabuye, E, Lutalo, T, Njua-Yafi, C, Nkuo-Akenji, T, Anchang-Kimbi, J, Mugri, R, Chi, H, Tata, R, Njumkeng, C, Dodoo, D, Achidi, E, Fernandes, J, Bache, EB, Matakala, K, Searle, K, Greenman, M, and Rainwater-Lovett, K

Published
2017

47. Natural antibody responses to Plasmodium falciparum MSP3 and GLURP(R0) antigens are associated with low parasite densities in malaria patients living in the Central Region of Ghana

Author

Amoah, L. E., Nuvor, S. V., Obboh, E. K., Acquah, F. K., Asare, K., Singh, S. K., Boampong, J. N., Theisen, M., Williamson, K. C., Amoah, L. E., Nuvor, S. V., Obboh, E. K., Acquah, F. K., Asare, K., Singh, S. K., Boampong, J. N., Theisen, M., and Williamson, K. C.

Abstract

Background: Plasmodium falciparum genetic diversity and multiplicity of infection (MOI) are parasite features that have been suggested to influence the acquisition of protective immunity against malaria. This study sought to assess the relationship between MOI and parasite density (PD) in malaria patients living in the Central Region of Ghana and to determine whether naturally occurring antibody levels against P. falciparum GLURP (PF3D7-1035300) and MSP3 (PF3D7-1035400) antigens are associated with decreased parasite load. Methods: Dried filter paper blood blots were obtained from children and adults diagnosed with uncomplicated P. falciparum malaria. Microscopy was used to estimate P. falciparum parasite density and polymerase chain reaction (PCR) amplification of the polymorphic regions of msp1 (PF3D7-0930300) and msp2 (PF3D7-0206800) was used for parasite genotyping and MOI determination. ELISA was used to measure the serum IgG concentration of R0 fragment of GLURP (GLURP(R0)) and MSP3 antibodies. Results: All 115 samples were positive for P. falciparum by PCR using either the msp1 or msp2 genotyping primer sets. The most prevalent msp1 and msp2 alleles were KI and 3D7, respectively. The geometric mean (GM) for MOI determined by both msp1 and msp2 genotyping was 1.3 for the entire population and was generally higher in children than in adults. Seropositivity was estimated at 67 and 63% for GLURP(R0) and MSP3 antibodies, respectively, and antibody titers were negatively correlated with parasite density. Conclusions: The negative correlation between naturally occurring GLURP(R0) and MSP3 antibody levels and parasite density observed in this study suggest that augmenting the antibody response with the GMZ2 vaccine could enhance protection in the Central Region of Ghana.

Published
2017

48. Synthetic TLR4 agonists enhance functional antibodies and CD4+ T-cell responses against the Plasmodium falciparum GMZ2.6C multi-stage vaccine antigen

Author

Baldwin, S.L., Roeffen, W., Singh, S.K, Tiendrebeogo, R.W., Christiansen, M., Beebe, E., Carter, D., Fox, C.B., Howard, R.F., Reed, S.G., Sauerwein, R.W., Theisen, M., Baldwin, S.L., Roeffen, W., Singh, S.K, Tiendrebeogo, R.W., Christiansen, M., Beebe, E., Carter, D., Fox, C.B., Howard, R.F., Reed, S.G., Sauerwein, R.W., and Theisen, M.

Abstract

Contains fulltext : 171587.pdf (publisher's version ) (Closed access), A subunit vaccine targeting both transmission and pathogenic asexual blood stages of Plasmodium falciparum, i.e., a multi-stage vaccine, could be a powerful tool to combat malaria. Here, we report production and characterization of the recombinant protein GMZ2.6C, which contains a fragment of the sexual-stage protein Pfs48/45-6C genetically fused to GMZ2, an asexual vaccine antigen in advanced clinical development. To select the most suitable vaccine formulation for downstream clinical studies, GMZ2.6C was tested with various immune modulators in different adjuvant formulations (stable emulsions, liposomes, and alum) in C57BL/6 mice. Some, but not all, formulations containing either the synthetic TLR4 agonist GLA or SLA elicited the highest parasite-specific antibody titers, the greatest IFN-gamma responses in CD4+ TH1 cells, and the highest percentage of multifunctional CD4+ T cells expressing IFN-gamma and TNF in response to GMZ2.6C. Both of these agonists have good safety records in humans.

Published
2016

50. Naturally acquired antibody responses to recombinant Pfs230 and Pfs48/45 transmission blocking vaccine candidates

Author

Jones, S, Grignard, L., Nebie, I., Chilongola, J., Dodoo, D., Sauerwein, R.W., Theisen, M., Roeffen, W.F., Singh, S.K, Singh, R.K., Kyei-Baafour, E., Tetteh, K., Drakeley, C., Bousema, T., Jones, S, Grignard, L., Nebie, I., Chilongola, J., Dodoo, D., Sauerwein, R.W., Theisen, M., Roeffen, W.F., Singh, S.K, Singh, R.K., Kyei-Baafour, E., Tetteh, K., Drakeley, C., and Bousema, T.

Abstract

Item does not contain fulltext, OBJECTIVES: Pfs48/45 and Pfs230 are Plasmodium falciparum sexual stage proteins and promising malaria transmission-blocking vaccine candidates. Antibody responses against these proteins may be naturally acquired and target antigens may be under selective pressure. This has consequences for the future evaluation of vaccine immunogenicity and efficacy in populations naturally exposed to malaria. METHODS: We determined naturally acquired antibody responses to the recombinant proteins Pfs48/45-10C and Pfs230-230CMB in children from three malaria endemic settings in Ghana, Tanzania and Burkina Faso. We also examined genetic polymorphisms in the P. falciparum gene pfs48/45. RESULTS: Antibody prevalence was 1.1-18.2% for 10C and 6.7-18.9% for 230CMB. In Burkina Faso we observed evidence of an age-dependent acquisition pattern for both 10C (p < 0.001) and 230CMB (p = 0.031). Membrane feeding assays on a separate dataset demonstrated an association between functional transmission reducing activity and antibody prevalence for both 10C (p = 0.017) and 230CMB (p = 0.049). 17 single nucleotide polymorphisms were found in pfs48/45 (from 126 samples), with 5 non-synonymous SNPs in the Pfs48/45 10C region. CONCLUSIONS: We conclude there are naturally acquired antibody responses to both vaccine candidates which have functional relevance by reducing the transmissibility of infected individuals. We identified genetic polymorphisms, in pfs48/45 which exhibited geographical specificity.

Published
2015

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