ArticleAIDS (London, England)2017
Preclinical evaluation of an mRNA HIV vaccine combining rationally selected antigenic sequences and adjuvant signals (HTI-TriMix).
Article in AIDS (London, England), 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 31 papers.
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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
31 citing papers in PubMed, 45 citations in OpenAlex.
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- Messenger RNA-Based Vaccines Against Infectious Diseases.Current topics in microbiology and immunology · 2022Review
- Demystifying mRNA vaccines: an emerging platform at the forefront of cryptic diseases.RNA biology · 2022Review
- Formulation and Delivery Technologies for mRNA Vaccines.Current topics in microbiology and immunology · 2022Article
- Messenger RNA-based vaccines: Past, present, and future directions in the context of the COVID-19 pandemic.Advanced drug delivery reviews · 2021Review
- Opportunities for innovation: Building on the success of lipid nanoparticle vaccines.Current opinion in colloid & interface science · 2021Review
- Strategies for controlling the innate immune activity of conventional and self-amplifying mRNA therapeutics: Getting the message across.Advanced drug delivery reviews · 2021Review
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- HIV and Messenger RNA (mRNA) Vaccine.Cureus · 2021Review
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- HIV mRNA Vaccines-Progress and Future Paths.Vaccines · 2021Review
- Exploration of Pattern Recognition Receptor Agonists as Candidate Adjuvants.Frontiers in cellular and infection microbiology · 2021Review
- Utilizing Computational Machine Learning Tools to Understand Immunogenic Breadth in the Context of a CD8 T-Cell Mediated HIV Response.Frontiers in immunology · 2021Article
- Modified mRNA-LNP Vaccines Confer Protection against Experimental DENV-2 Infection in Mice.Molecular therapy. Methods & clinical development · 2020Article
- mRNA Vaccine Era-Mechanisms, Drug Platform and Clinical Prospection.International journal of molecular sciences · 2020Review
- The Evolution of Dendritic Cell Immunotherapy against HIV-1 Infection: Improvements and Outlook.Journal of immunology research · 2020Review
Corrections and comments
- Commented on by
- Erratum issued
Authors and funding
13 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe development of a prophylactic vaccine against HIV-1 has so far not been successful. Therefore, attention has shifted more and more toward the development of novel therapeutic vaccines. Here, we evaluated a new mRNA-based therapeutic vaccine against HIV-1-encoding activation signals (TriMix: CD40L + CD70 + caTLR4) combined with rationally selected antigenic sequences [HIVACAT T-cell immunogen (HTI)] sequence: comprises 16 joined fragments from Gag, Pol, Vif, and Nef).
methodsFor this purpose, peripheral blood mononuclear cells from HIV-1-infected individuals on cART, lymph node explants from noninfected humans, and splenocytes from immunized mice were collected and several immune functions were measured.
resultsElectroporation of immature monocyte-derived dendritic cells from HIV-infected patients with mRNA encoding HTI + TriMix potently activated dendritic cells which resulted in upregulation of maturation markers and cytokine production and T-cell stimulation, as evidenced by enhanced proliferation and cytokine secretion (IFN-γ). Responses were HIV specific and were predominantly targeted against the sequences included in HTI. These findings were confirmed in human lymph node explants exposed to HTI + TriMix mRNA. Intranodal immunizations with HTI mRNA in a mouse model increased antigen-specific cytotoxic T-lymphocyte responses. The addition of TriMix further enhanced cytotoxic responses.
conclusionOur results suggest that uptake of mRNA, encoding strong activation signals and a potent HIV antigen, confers a T-cell stimulatory capacity to dendritic cells and enhances their ability to stimulate antigen-specific immunity. These findings may pave the way for therapeutic HIV vaccine strategies based on antigen-encoding RNA to specifically target antigen-presenting cells.
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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.