Article
Multidisciplinary Sciences
Kaituo Wang, Robert Dagil, Thomas Lavstsen, Sandeep K. Misra, Charlotte B. Spliid, Yong Wang, Tobias Gustavsson, Daniel R. Sandoval, Elena Ethel Vidal-Calvo, Swati Choudhary, Mette O. Agerbaek, Kresten Lindorff-Larsen, Morten A. Nielsen, Thor G. Theander, Joshua S. Sharp, Thomas Mandel Clausen, Pontus Gourdon, Ali Salanti
Summary: The study presents cryo-EM structures of VAR2CSA and placental CS, identifying molecular interactions that could guide the design of placental malaria vaccines.
NATURE COMMUNICATIONS
(2021)
Review
Immunology
Alice Tomlinson, Jean-Philippe Semblat, Benoit Gamain, Arnaud Chene
Summary: Placental malaria is characterized by accumulation of infected erythrocytes in the placenta, causing local inflammation and severe clinical outcomes for both mother and child. The malaria parasite uses evasion mechanisms to ensure its survival during placental malaria.
FRONTIERS IN IMMUNOLOGY
(2021)
Review
Parasitology
Sedami Gnidehou, Stephanie K. Yanow
Summary: The detection of VAR2CSA IgGs in non-pregnant populations raises questions about their specificity and acquisition mechanisms, necessitating further investigation into their biological relevance and potential acquisition mechanisms in these populations.
TRENDS IN PARASITOLOGY
(2021)
Article
Microbiology
Torben Rehn, Pedro Lubiana, Thi Huyen Trang Nguyen, Eva Pansegrau, Marius Schmitt, Lisa Katharina Roth, Jana Brehmer, Thomas Roeder, Daniel Cadar, Nahla Galal Metwally, Iris Bruchhaus
Summary: This study reveals the ability of P. falciparum expressing vir genes to bind to CD36, and finds that this cytoadhesion is dependent on the presence of PfEMP1 proteins. These findings are important for studying VIR proteins.
Article
Medicine, General & Internal
Wenn-Chyau Lee, Bruce Russell, Bernett Lee, Cindy S. Chu, Aung Pyae Phyo, Kanlaya Sriprawat, Yee-Ling Lau, Francois Nosten, Laurent Renia
Summary: Brief exposure to artesunate (AS) stimulates rosetting, with AS-resistant isolates forming more rosettes rapidly for protection. Deletions in genes associated with AS-mediated rosetting are significantly selected in the parasite population, along with the K13 mutations as a marker of ART resistance.
Article
Biology
Jonathan P. Renn, Justin Y. A. Doritchamou, Bergeline C. Nguemwo Tentokam, Robert D. Morrison, Matthew Cowles, Martin Burkhardt, Rui Ma, Niraj H. Tolia, Michal Fried, Patrick E. Duffy
Summary: The study compares the antigenicity and receptor binding affinity of different allelic variants of the potential placental malaria vaccine candidate VAR2CSA in blood samples from pregnant women. The data suggest that inter-allelic differences may impact clinical presentation heterogeneity and have implications for vaccine design.
COMMUNICATIONS BIOLOGY
(2021)
Article
Multidisciplinary Sciences
Katharina Preissinger, Miklos Kellermayer, Beata G. Vertessy, Istvan Kezsmarki, Janos Torok
Summary: Malaria, a global burden with millions of annual cases, requires improvement in diagnostic techniques for its elimination. This study introduces a novel neural network-based scheme capable of high-speed and accurate classification of malaria infected red blood cells. The smart reduction of data dimension significantly improves the performance and applicability of the method.
SCIENTIFIC REPORTS
(2022)
Article
Biochemistry & Molecular Biology
Tamir Zelter, Jacob Strahilevitz, Karina Simantov, Olga Yajuk, Yvonne Adams, Anja Ramstedt Jensen, Ron Dzikowski, Zvi Granot
Summary: Neutrophils can recognize and kill blood-stage Plasmodium falciparum, with neutrophil ICAM-1 and specific PfEMP1 implicated in cerebral malaria being key molecules involved in this killing.
Article
Immunology
Koko Vanda, Naveen Bobbili, Masako Matsunaga, John J. Chen, Ali Salanti, Rose F. G. Leke, Diane Wallace Taylor
Summary: The study found that high avidity antibodies to VAR2CSA increase with gravidity in women, especially during the second pregnancy. These antibodies are mainly directed against a specific region of VAR2CSA and have a positive impact on pregnancy outcomes for women in urban areas.
FRONTIERS IN IMMUNOLOGY
(2021)
Review
Immunology
Benoit Gamain, Arnaud Chene, Nicola K. Viebig, Nicaise Tuikue Ndam, Morten A. Nielsen
Summary: Adults in malaria endemic areas usually acquire clinical immunity against malaria, but pregnant women, especially during their first pregnancies, are susceptible to placental malaria. Placental malaria is characterized by the accumulation of P. falciparum-infected erythrocytes and monocytes in the placenta, leading to maternal anaemia, hypertension, and fetal growth retardation. However, the prevalence of placental malaria decreases significantly with successive pregnancies.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Medicine, General & Internal
Rebecca Webster, Silvana Sekuloski, Anand Odedra, Stephen Woolley, Helen Jennings, Fiona Amante, Katharine R. Trenholme, Julie Healer, Alan F. Cowman, Emily M. Eriksson, Priyanka Sathe, Jocelyn Penington, Adam J. Blanch, Matthew W. A. Dixon, Leann Tilley, Michael F. Duffy, Alister Craig, Janet Storm, Jo-Anne Chan, Krystal Evans, Anthony T. Papenfuss, Louis Schofield, Paul Griffin, Bridget E. Barber, Dean Andrew, Michelle J. Boyle, Fabian de Labastida Rivera, Christian Engwerda, James S. McCarthy
Summary: A genetically attenuated blood-stage malaria vaccine was developed and tested in healthy volunteers, showing immunogenicity but causing significant parasitemia at high doses.
Article
Microbiology
Emily M. Stucke, Antoine Dara, Ankit Dwivedi, Theresa K. Hodges, Sandra Ott, Drissa Coulibaly, Abdoulaye K. Kone, Karim Traore, Boureima Guindo, Bourama M. Tangara, Amadou Niangaly, Modibo Daou, Issa Diarra, Youssouf Tolo, Mody Sissoko, Luke J. Tallon, Lisa Sadzewicz, Albert E. Zhou, Matthew B. Laurens, Amed Ouattara, Bourema Kouriba, Ogobara K. Doumbo, Shannon Takala-Harrison, David Serre, Christopher Plowe, Mahamadou A. Thera, Mark A. Travassos, Joana C. Silva
Summary: Genes encoding the highly diverse Plasmodium falciparum erythrocyte membrane protein-1 (PfEMP1) antigens play a critical role in immune evasion and infected erythrocyte sequestration. Enriching for parasite RNA in clinical samples using a custom capture array allowed for the identification and annotation of var-like transcripts, particularly in samples with low parasitemia. This method has broad applicability to other highly diverse antigens from different parasites and pathogens.
Article
Immunology
Alistair R. D. McLean, D. Herbert Opi, Danielle Stanisic, Julia C. Cutts, Gaoqian Feng, Alice Ura, Ivo Mueller, Stephen J. Rogerson, James G. Beeson, Freya J. Fowkes
Summary: Interventions targeting VAR2CSA antibody levels may impact placental infection, birthweight, and gestational age at delivery in pregnant women infected with P. falciparum by mid-pregnancy. Higher levels of VAR2CSA antibodies in women already infected by mid-pregnancy may contribute to protecting the fetus and reducing the risk of placental infection, while higher levels of VAR2CSA antibodies in women not infected at enrolment may increase the risk of placental infection.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Immunology
Mary Lopez-Perez, Firmine Viwami, Zakaria Seidu, Anja T. R. Jensen, Justin Doritchamou, Nicaise Tuikue Ndam, Lars Hviid
Summary: The study found that HbAS does not provide protection against placental malaria infection in pregnant women, and the immune levels to specific PfEMP1 variants were similar in HbAS and HbAA women. Women with placental malaria had lower levels of anti-VAR2CSA specific IgG.
OPEN FORUM INFECTIOUS DISEASES
(2021)
Article
Immunology
Gladys J. Keitany, Bethany J. Jenkins, Harold T. Obiakor, Shaji Daniel, Atis Muehlenbachs, Jean-Philippe Semblat, Benoit Gamain, Justin Y. A. Doritchamou, Sanjay A. Desai, Nicholas J. MacDonald, David L. Narum, Robert Morrison, Tracy Saveria, Marissa Vignali, Andrew Oleinikov, Michal Fried, Patrick E. Duffy
Summary: This study characterizes an invariant protein associated with placental malaria (PM), PfCSA-L, which binds both VAR2CSA and placental CSA with high affinity. Unlike VAR2CSA, PfCSA-L is peripherally associated with the outer surface of knobs through protein-protein interactions with VAR2CSA. The findings suggest that sequestration of infected red blood cells (iRBCs) involves complexes of invariant and variant surface proteins, allowing parasites to maintain diversity and function on the iRBC surface.
JOURNAL OF INFECTIOUS DISEASES
(2022)
Article
Immunology
Louise Goksoyr, Magdalena Skrzypczak, Maureen Sampson, Morten A. Nielsen, Ali Salanti, Thor G. Theander, Alan T. Remaley, Willem A. De Jongh, Adam F. Sander
Summary: Administration of PCSK9-specific monoclonal antibodies and peptide-based PCSK9 vaccines can reduce plasma LDL cholesterol by blocking PCSK9. However, these treatments also increase plasma PCSK9 levels due to the formation of immune complexes. A study using a cVLP-based vaccine platform shows that the FL PCSK9 cVLP vaccine has an enhanced ability to opsonize and clear plasma PCSK9. These findings have implications for the design of vaccines that can effectively mediate opsonization and immune clearance of target antigens.
Article
Infectious Diseases
Merel J. Smit, Adam F. Sander, Maud B. P. A. Ariaans, Cyrielle Fougeroux, Constanze Heinzel, Rolf Fendel, Meral Esen, Peter G. Kremsner, Rob ter Heine, Heiman F. Wertheim, Manja Idorn, Alexander P. Underwood, Alekxander Binderup, Santseharay Ramirez, Jens Bukh, Max Soegaard, Sayit M. Erdogan, Tobias Gustavsson, Stine Clemmensen, Thor G. Theander, Lancet Microbe, Ali Salanti, Mette Hamborg, Willem A. de Jongh, Matthew B. B. McCall, Morten A. Nielsen, Benjamin G. Mordmuller
Summary: A clinical trial was conducted in the Netherlands to test a cVLP-based COVID-19 vaccine. The results showed that the vaccine exhibited high immunogenicity at antigen levels of 25-70 mu g and had high virus neutralization activity against major SARS-CoV-2 variants.
Article
Oncology
Nanna Skeltved, Mie A. A. Nordmaj, Nicolai T. T. Berendtsen, Robert Dagil, Emilie M. R. Stormer, Nader Al-Nakouzi, Ke Jiang, Alexandra Aicher, Christopher Heeschen, Tobias Gustavsson, Swati Choudhary, Ismail Gogenur, Jan P. P. Christensen, Thor G. G. Theander, Mads Daugaard, Ali Salanti, Morten A. A. Nielsen
Summary: The malaria protein VAR2CSA has anti-tumor efficacy by binding to oncofetal chondroitin sulfate (ofCS). Combining V-aCD3 with an immune checkpoint inhibitor enhances the anti-tumor effects, leading to complete elimination of solid tumors in mice.
JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH
(2023)
Article
Immunology
Jeong In Yang, Dagoberto Sepulveda, Irina Vardia, Jakob Skov, Louise Goksoyr, Adam F. F. Sander, Niels Lorenzen
Summary: This study aimed to develop and test a recombinant alternative vaccine based on virus-like particles (VLPs) decorated with VapA protein as the key structural surface protein for combating A. salmonicida bacterial disease. The results showed that rainbow trout vaccinated with VapA-VLP vaccines exhibited comparable protection to the bacterin-based vaccine and produced a strong VapA-specific antibody response.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Immunology
Melanie R. Walker, Manja Idorn, Anja Bennett, Max Sogaard, Ali Salanti, Sisse B. Ditlev, Lea Barfod
Summary: The study found that new variants of the SARS-CoV-2 virus are less susceptible to vaccine-induced immunity, leading to breakthrough infections among vaccinated individuals. The research also revealed the significant role of different types and subclasses of immunoglobulins in the immune response during vaccination and breakthrough infections.
IMMUNITY INFLAMMATION AND DISEASE
(2023)
Article
Veterinary Sciences
Justin Doritchamou, Morten A. Nielsen, Arnaud Chene, Nicola K. Viebig, Lynn E. Lambert, Adam F. Sander, Jean-Philippe Semblat, Sophia Hundt, Sachy Orr-Gonzalez, Christoph Mikkel Janitzek, Alicia J. Spiegel, Stine B. Clemmensen, Marvin L. Thomas, Martha C. Nason, Maryonne Snow-Smith, Emma K. Barnafo, Joseph Shiloach, Beth B. Chen, Steven Nadakal, Kendrick Highsmith, Tarik Ouahes, Solomon Conteh, Ankur Sharma, Holly Torano, Brandi Butler, Karine Reiter, Kelly M. Rausch, Puthupparampil V. Scaria, Charles Anderson, David L. Narum, Ali Salanti, Michal Fried, Thor G. Theander, Benoit Gamain, Patrick E. Duffy
Summary: This study investigated the functional antibody response and antibody boosting during PM episodes in Aotus monkeys immunized with placental malaria vaccine (PMV) candidates. The results showed that PMV candidates induced functional antibodies with limited heterologous activity in the monkeys, similar to human responses. The Aotus model appears to be suitable for preclinical downselection of PMV candidates and assessment of antibody boosting.
Article
Biochemistry & Molecular Biology
Sai Sundar Rajan Raghavan, Louise Turner, Rasmus W. Jensen, Nicolai Tidemand Johansen, Daniel Skjold Jensen, Pontus Gourdon, Jinqiu Zhang, Yong Wang, Thor Grundtvig Theander, Kaituo Wang, Thomas Lavstsen
Summary: Using Cryo-EM and PfEMP1 sequence diversity analysis, it was found that the CIDRa1 domains of group A PfEMP1 interact with the adjacent DBLa1 domain through central, conserved residues of the EPCR-binding site to form a compact conformation. Upon EPCR binding, the DBLa1 domain is displaced, and the EPCR-binding helix of CIDRa1 undergoes a rearrangement to reach a stable EPCR-bound conformation. This may represent a conformational masking mechanism for immune evasion in the PfEMP1 family.
Article
Multidisciplinary Sciences
Julie Van Coillie, Tamas Pongracz, Tonci Sustic, Wenjun Wang, Jan Nouta, Mathieu Le Gars, Sofie Keijzer, Federica Linty, Olvi Cristianawati, Jim B. D. Keijser, Remco Visser, Lonneke A. van Vught, Marleen A. Slim, Niels van Mourik, Merel J. Smit, Adam Sander, David E. Schmidt, Maurice Steenhuis, Theo Rispens, Morten A. Nielsen, Benjamin G. Mordmueller, Alexander P. J. Vlaar, C. Ellen van der Schoot, Ramon Roozendaal, Manfred Wuhrer, Gestur Vidarsson
Summary: In this study, the glycosylation profiles of anti-S IgG1 Fc in response to mRNA, adenoviral, and protein-based COVID-19 vaccines were compared using mass spectrometry (MS). The results showed variations in the glycosylation patterns between different vaccine platforms and individuals, but overall, vaccine-induced anti-S IgG glycosylation was dynamic with marked overlaps.