Article
Biology
Justin Y. A. Doritchamou, Jonathan P. Renn, Bethany Jenkins, Almahamoudou Mahamar, Alassane Dicko, Michal Fried, Patrick E. Duffy
Summary: This study found that a single VAR2CSA ectodomain variant displays conserved epitopes that are targeted by neutralizing antibodies shared by multiple parasite strains, suggesting that a broadly effective placental malaria vaccine can be achieved with a limited number of VAR2CSA variants.
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)
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)
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)
Article
Microbiology
Justin Y. A. Doritchamou, Jonathan P. Renn, Lars Hviid, Patrick E. Duffy
Summary: VAR2CSA is a Plasmodium falciparum variant surface antigen that causes placental malaria by binding infected erythrocytes to chondroitin sulfate A. The high polymorphism in VAR2CSA sequences hampers the development of a broadly neutralizing vaccine. Recent research reveals that a human monoclonal antibody called PAM1.4 binds to conserved residues of different VAR2CSA subfragments, indicating its potential for broad reactivity. Understanding the critical residues within the PAM1.4 binding epitope of VAR2CSA can help identify similar epitopes targeted by broadly neutralizing antibodies and decipher the immune evasion mechanisms employed by placenta-binding parasites through VAR2CSA polymorphism.
Article
Immunology
Isaac Ssewanyana, John Rek, Isabel Rodriguez, Lindsey Wu, Emmanuel Arinaitwe, Joaniter I. Nankabirwa, James G. Beeson, Harriet Mayanja-Kizza, Philip J. Rosenthal, Grant Dorsey, Moses R. Kamya, Chris Drakeley, Bryan Greenhouse, Kevin K. A. Tetteh
Summary: The study revealed that the decay rate of total IgG following infection decreased with age during declining malaria transmission, and the increase in avidity index post-infection was largely due to the rapid loss of non-avid total IgG. Further research is needed to understand the functional differences between IgG1 and IgG3 to determine their role in protective immunity to malaria.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Infectious Diseases
Jasmita Gill, Soumyananda Chakraborti, Praveen Bharti, Amit Sharma
Summary: Placental malaria caused by Plasmodium falciparum protein VAR2CSA poses a significant health burden in Africa, with studies revealing mutations in CSA-binding residues in field isolates. Structural analysis showed significant polymorphisms on the ligand binding surfaces, highlighting concerns for developing vaccines based on VAR2CSA.
INTERNATIONAL JOURNAL OF INFECTIOUS DISEASES
(2021)
Review
Immunology
Justin Yai Alamou Doritchamou, Jennifer Suurbaar, Nicaise Tuikue Ndam
Summary: Phase I trials of PAMVAC and PRIMVAC VAR2CSA vaccines have shown satisfactory results with regards to safety and immunogenicity. The second generation of VAR2CSA-based vaccines could benefit from optimization approaches to broaden the activity spectrum against various placenta-binding isolates through continued advances in structural understanding of the interaction with CSA.
EXPERT REVIEW OF VACCINES
(2021)
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
Medicine, General & Internal
D. Herbert Opi, Michelle J. Boyle, Alistair R. D. McLean, Linda Reiling, Jo-Anne Chan, Danielle Stanisic, Alice Ura, Ivo Mueller, Freya J. Fowkes, Stephen J. Rogerson, James G. Beeson
Summary: The study identified pregnant women who developed antibodies that effectively promoted complement fixation on placental-binding pRBCs, associated with protection against MiP. These complement-fixing antibodies primarily targeted a specific variant of PfEMP1 called VAR2CSA, and complement enhanced the ability of antibodies to inhibit pRBC binding to CSA for increased protection.
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
Immunology
Adebimpe Fasanya, Nurat Mohammed, Bandar Hasan Saleh, Muyideen Kolapo Tijani, Alexandra Teleka, Maria del Pilar Quintana, Lars Hviid, Kristina E. M. Persson
Summary: Anemia is a common complication in pregnant women with malaria in endemic regions. Antibodies against Phosphatidylserine (PS) may contribute to anemia through destruction of uninfected red blood cells. Levels of anti-PS IgG antibodies were measured in pregnant women in Nigeria and correlated with anemia and immune parameters. The study suggests that lower levels of anti-PS in multigravidae may be beneficial in avoiding anemia.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(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
Microbiology
Eldin Talundzic, Stephen Scott, Simon O. Owino, David S. Campo, Naomi W. Lucchi, Venkatachalam Udhayakumar, Julie M. Moore, David S. Peterson
Summary: This study reveals the association between the genetic diversity of the Plasmodium falciparum protein VAR2CSA and immune evasion and virulence, highlighting its significance for vaccine development.
Article
Biochemistry & Molecular Biology
Mashanipalya G. Jagadeeshaprasad, Lovely Gautam, Maria C. Bewley, Suchi Goel, Reetesh R. Akhouri, D. Channe Gowda
Summary: VAR2CSA protein, which consists of multiple domains, is involved in the adherence of parasite-infected red blood cells to chondroitin 4-sulfate (C4S) in the placenta, contributing to placental malaria. A better understanding of the VAR2CSA structure can aid in the development of strategies to treat placental malaria.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2023)