ArticleJournal of immunology (Baltimore, Md. : 1950)2011
Combining liver- and blood-stage malaria viral-vectored vaccines: investigating mechanisms of CD8+ T cell interference.
Article in Journal of immunology (Baltimore, Md. : 1950), 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
What it found
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
32 citing papers in PubMed, 40 citations in OpenAlex.
- ChAd63-MVA-vectored blood-stage malaria vaccines targeting MSP1 and AMA1: assessment of efficacy against mosquito bite challenge in humans.Molecular therapy : the journal of the American Society of Gene Therapy · 2012Trial
- Non-cytolytic re-engineering of a viral vaccine vector enables durable effector-memory T cell immunity by reinforcing type I IFN induction.Molecular therapy. Nucleic acids · 2026Article
- Immunogenicity of a Plasmodium vivax vaccine based on the duffy binding protein formulated using adjuvants compatible for use in humans.Scientific reports · 2023Article
- Inclusion of an OptimizedJournal of immunology (Baltimore, Md. : 1950) · 2021Article
- A Multi-Filovirus Vaccine Candidate: Co-Expression of Ebola, Sudan, and Marburg Antigens in a Single Vector.Vaccines · 2020Article
- Immunity against sexual stage Plasmodium falciparum and Plasmodium vivax parasites.Immunological reviews · 2020Review
- Maintaining immunogenicity of blood stage and sexual stage subunit malaria vaccines when formulated in combination.PloS one · 2020Article
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- A Viral-Vectored Multi-Stage Malaria Vaccine Regimen With Protective and Transmission-Blocking Efficacies.Frontiers in immunology · 2019Article
- Evaluation of a Plasmodium-Specific Carrier Protein To Enhance Production of RecombinantInfection and immunity · 2018Article
- Novel Plasmodium antigens identified via genome-based antibody screen induce protection associated with polyfunctional T cell responses.Scientific reports · 2017Article
- Enhancing protective immunity to malaria with a highly immunogenic virus-like particle vaccine.Scientific reports · 2017Article
- Assessment of the Plasmodium falciparum Preerythrocytic Antigen UIS3 as a Potential Candidate for a Malaria Vaccine.Infection and immunity · 2017Article
- Assessment of Antibodies Induced by Multivalent Transmission-Blocking Malaria Vaccines.Frontiers in immunology · 2017Article
- Germinal Center B Cell and T Follicular Helper Cell Responses to Viral Vector and Protein-in-Adjuvant Vaccines.Journal of immunology (Baltimore, Md. : 1950) · 2016Article
- Transmission blocking potency and immunogenicity of a plant-produced Pvs25-based subunit vaccine against Plasmodium vivax.Vaccine · 2016Article
- Immunogenicity of a chimeric Plasmodium falciparum merozoite surface protein vaccine in Aotus monkeys.Malaria journal · 2016Article
- Recombinant modified vaccinia virus Ankara-based malaria vaccines.Expert review of vaccines · 2016Review
- Tailoring a Combination Preerythrocytic Malaria Vaccine.Infection and immunity · 2015Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Replication-deficient adenovirus and modified vaccinia virus Ankara (MVA) vectors expressing single pre-erythrocytic or blood-stage Plasmodium falciparum Ags have entered clinical testing using a heterologous prime-boost immunization approach. In this study, we investigated the utility of the same immunization regimen when combining viral vectored vaccines expressing the 42-kDa C terminus of the blood-stage Ag merozoite surface protein 1 and the pre-erythrocytic Ag circumsporozoite protein in the Plasmodium yoelii mouse model. We find that vaccine coadministration leads to maintained Ab responses and efficacy against blood-stage infection, but reduced secondary CD8(+) T cell responses against both Ags and efficacy against liver-stage infection. CD8(+) T cell interference can be minimized by coadministering the MVA vaccines at separate sites, resulting in enhanced liver-stage efficacy in mice immunized against both Ags compared with just one. CD8(+) T cell interference (following MVA coadministration as a mixture) may be caused partly by a lack of physiologic space for high-magnitude responses against multiple Ags, but is not caused by competition for presentation of Ag on MHC class I molecules, nor is it due to restricted T cell access to APCs presenting both Ags. Instead, enhanced killing of peptide-pulsed cells is observed in mice possessing pre-existing T cells against two Ags compared with just one, suggesting that priming against multiple Ags may in part reduce the potency of multiantigen MVA vectors to stimulate secondary CD8(+) T cell responses. These data have important implications for the development of a multistage or multicomponent viral vectored malaria vaccine for use in humans.
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Registered trials
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.