ArticlePloS one2013
DNA prime/Adenovirus boost malaria vaccine encoding P. falciparum CSP and AMA1 induces sterile protection associated with cell-mediated immunity.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 91 papers, 1 of them a synthesis that pooled it.
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Who cites it
91 citing papers in PubMed, 1 synthesis or guideline pooled it, 142 citations in OpenAlex.
- Neutropenia as an Adverse Event following Vaccination: Results from Randomized Clinical Trials in Healthy Adults and Systematic Review.PloS one · 2016Pooled it
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- Strain-specific Plasmodium falciparum growth inhibition among Malian children immunized with a blood-stage malaria vaccine.PloS one · 2017Trial
- Demonstration of the Blood-Stage Plasmodium falciparum Controlled Human Malaria Infection Model to Assess Efficacy of the P. falciparum Apical Membrane Antigen 1 Vaccine, FMP2.1/AS01.The Journal of infectious diseases · 2016Trial
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- Antibody and T-cell responses associated with experimental human malaria infection or vaccination show limited relationships.Immunology · 2015Trial
- Evaluation of the efficacy of ChAd63-MVA vectored vaccines expressing circumsporozoite protein and ME-TRAP against controlled human malaria infection in malaria-naive individuals.The Journal of infectious diseases · 2015Trial
- Discovery of Novel Plasmodium falciparum Pre-Erythrocytic Antigens for Vaccine Development.PloS one · 2015Trial
- Controlled Human Malaria Infection (CHMI) differentially affects cell-mediated and antibody responses to CSP and AMA1 induced by adenovirus vaccines with and without DNA-priming.Human vaccines & immunotherapeutics · 2015Trial
- Trial
- Randomized, placebo-controlled trial to assess the safety and immunogenicity of an adenovirus type 35-based circumsporozoite malaria vaccine in healthy adults.Human vaccines & immunotherapeutics · 2013Trial
- Recent Advances, Bottlenecks, and Future Directions inVaccines · 2026Review
- Controlled human malaria infection studies: insights into recent advances and key immunological and ethical implementation lessons.Frontiers in immunology · 2025Review
- Natural selection on apical membrane antigen 1 (AMA1) of an emerging zoonotic malaria parasite Plasmodium inui.Scientific reports · 2024Article
- Vaccines and monoclonal antibodies: new tools for malaria control.Clinical microbiology reviews · 2024Review
- High-Throughput Screening for the Prevalence of Neutralizing Antibodies against Human Adenovirus Serotype 5.Vaccines · 2024Article
- Controlled Human Malaria Infection Studies in Africa-Past, Present, and Future.Current topics in microbiology and immunology · 2024Review
- Malaria Vaccines: Progress to Date.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2023Review
- The Complexity of Interferon Signaling in Host Defense against Protozoan Parasite Infection.Pathogens (Basel, Switzerland) · 2023Review
31 more citing papers are in PubMed but not listed here.
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Authors and funding
46 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundGene-based vaccination using prime/boost regimens protects animals and humans against malaria, inducing cell-mediated responses that in animal models target liver stage malaria parasites. We tested a DNA prime/adenovirus boost malaria vaccine in a Phase 1 clinical trial with controlled human malaria infection. METHODOLOGY/PRINCIPAL
findingsThe vaccine regimen was three monthly doses of two DNA plasmids (DNA) followed four months later by a single boost with two non-replicating human serotype 5 adenovirus vectors (Ad). The constructs encoded genes expressing P. falciparum circumsporozoite protein (CSP) and apical membrane antigen-1 (AMA1). The regimen was safe and well-tolerated, with mostly mild adverse events that occurred at the site of injection. Only one AE (diarrhea), possibly related to immunization, was severe (Grade 3), preventing daily activities. Four weeks after the Ad boost, 15 study subjects were challenged with P. falciparum sporozoites by mosquito bite, and four (27%) were sterilely protected. Antibody responses by ELISA rose after Ad boost but were low (CSP geometric mean titer 210, range 44-817; AMA1 geometric mean micrograms/milliliter 11.9, range 1.5-102) and were not associated with protection. Ex vivo IFN-γ ELISpot responses after Ad boost were modest (CSP geometric mean spot forming cells/million peripheral blood mononuclear cells 86, range 13-408; AMA1 348, range 88-1270) and were highest in three protected subjects. ELISpot responses to AMA1 were significantly associated with protection (p = 0.019). Flow cytometry identified predominant IFN-γ mono-secreting CD8+ T cell responses in three protected subjects. No subjects with high pre-existing anti-Ad5 neutralizing antibodies were protected but the association was not statistically significant. SIGNIFICANCE: The DNA/Ad regimen provided the highest sterile immunity achieved against malaria following immunization with a gene-based subunit vaccine (27%). Protection was associated with cell-mediated immunity to AMA1, with CSP probably contributing. Substituting a low seroprevalence vector for Ad5 and supplementing CSP/AMA1 with additional antigens may improve protection.
trial registrationClinicalTrials.govNCT00870987.
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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.