ArticleBMC medicine2018
Human antibodies activate complement against Plasmodium falciparum sporozoites, and are associated with protection against malaria in children.
Article in BMC medicine, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 69 papers.
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Who cites it
69 citing papers in PubMed, 115 citations in OpenAlex.
- Antibody fine specificity correlates with protection from malaria for the RTS,S vaccine in young African children: A post hoc analysis of a phase IIb randomised controlled trial.PLoS medicine · 2026Trial
- R21/Matrix-M malaria vaccine drives diverse immune responses in pre-exposed adults: insights from a phase IIb controlled human malaria infection trial.Frontiers in immunology · 2025Trial
- Safety and protective efficacy of PfSPZ Vaccine administered to HIV-negative and -positive Tanzanian adults.The Journal of clinical investigation · 2024Trial
- Induction, decay, and determinants of functional antibodies following vaccination with the RTS,S malaria vaccine in young children.BMC medicine · 2022Trial
- Multifunctional Antibodies Are Induced by the RTS,S Malaria Vaccine and Associated With Protection in a Phase 1/2a Trial.The Journal of infectious diseases · 2021Trial
- A longitudinal study of children identifies antibody Fc-mediated functions and antigen targets of immunity to Plasmodium vivax malaria.Immunity · 2026Article
- Targeting a malaria merozoite surface protein with mRNA vaccine generates multifunctional antibodies.Frontiers in immunology · 2026Article
- Relationship between antibody avidity, Fc-mediated functional activity and longevity of malaria vaccine responses in clinical trials.Frontiers in immunology · 2026Article
- Influence of biophysical and biochemical cues on Plasmodium sporozoite dynamics in skin tissue.Parasites & vectors · 2025Review
- A whole blood assay for antibody dependent phagocytosis of Plasmodium falciparum infected erythrocytes.Communications medicine · 2025Article
- Role of malaria exposure and off-target responses on RTS,S/AS02NPJ vaccines · 2025Article
- FcγR binding differentially contributes to protection by two human monoclonal antibodies targetingScience translational medicine · 2025Article
- Antibody correlates of risk of clinical malaria in an area of low and unstable malaria transmission in western Kenya.Malaria journal · 2025Article
- Malaria exposure remodels the plasma proteome of Ghanaian children.BMC infectious diseases · 2025Article
- Targeting mucosal immunity in malaria control: the underexplored role of IgA.Frontiers in malaria · 2025Article
- Development of high affinity antibodies toFrontiers in immunology · 2025Article
- Induction of Fc-dependent functional antibodies against different variants of SARS-CoV-2 varies by vaccine type and prior infection.Communications medicine · 2024Article
- PfSPZ Vaccine induces focused humoral immune response in HIV positive and negative Tanzanian adults.EBioMedicine · 2024Article
- A systems serology approach to identifying key antibody correlates of protection from cerebral malaria in Malawian children.BMC medicine · 2024Article
- Monoclonal antibodies to the circumsporozoite proteins as an emerging tool for malaria prevention.Nature immunology · 2024Review
9 more citing papers are in PubMed but not listed here.
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Authors and funding
11 authors at 7 institutions in 5 countries.
Funding
Abstract
backgroundAntibodies targeting Plasmodium falciparum sporozoites play a key role in human immunity to malaria. However, antibody mechanisms that neutralize sporozoites are poorly understood. This has been a major constraint in developing highly efficacious vaccines, as we lack strong correlates of protective immunity.
methodsWe quantified the ability of human antibodies from malaria-exposed populations to interact with human complement, examined the functional effects of complement activity against P. falciparum sporozoites in vitro, and identified targets of functional antibodies. In children and adults from malaria-endemic regions, we determined the acquisition of complement-fixing antibodies to sporozoites and their relationship with antibody isotypes and subclasses. We also investigated associations with protective immunity in a longitudinal cohort of children (n = 206) residing in a malaria-endemic region.
resultsWe found that antibodies to the major sporozoite surface antigen, circumsporozoite protein (CSP), were predominately IgG1, IgG3, and IgM, and could interact with complement through recruitment of C1q and activation of the classical pathway. The central repeat region of CSP, included in leading vaccines, was a key target of complement-fixing antibodies. We show that antibodies activate human complement on P. falciparum sporozoites, which consequently inhibited hepatocyte cell traversal that is essential for establishing liver-stage infection, and led to sporozoite death in vitro. The natural acquisition of complement-fixing antibodies in malaria-exposed populations was age-dependent, and was acquired more slowly to sporozoite antigens than to merozoite antigens. In a longitudinal cohort of children, high levels of complement-fixing antibodies were significantly associated with protection against clinical malaria.
conclusionsThese novel findings point to complement activation by antibodies as an important mechanism of anti-sporozoite human immunity, thereby enabling new strategies for developing highly efficacious malaria vaccines. We also present evidence that complement-fixing antibodies may be a valuable correlate of protective immunity in humans.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.