ArticleProceedings of the National Academy of Sciences of the United States of America2013
The adjuvant MF59 induces ATP release from muscle that potentiates response to vaccination.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 93 papers.
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Who cites it
93 citing papers in PubMed, 157 citations in OpenAlex.
- Trial
- Immunogenicity and Safety of an MF59-adjuvanted Quadrivalent Seasonal Influenza Vaccine in Young Children at High Risk of Influenza-associated Complications: A Phase III, Randomized, Observer-blind, Multicenter Clinical Trial.The Pediatric infectious disease journal · 2020Trial
- Rational design of next-generation vaccine adjuvants: From molecular mechanisms to hybrid delivery platforms.Human vaccines & immunotherapeutics · 2026Review
- Autologous erythrocyte microparticles drive antitumour T cell immunity via haem-mediated dendritic cell activation.Nature biomedical engineering · 2026Article
- Characterization of Seasonal Trivalent Influenza Vaccine Formulated with Different Ratios (Vaccines · 2026Article
- Lyophilizable Thermostable Nano-Aluminum Adjuvant and Combinations Induced Robust Antigen-Specific Humoral and Cellular Immunity in Mice.Advanced healthcare materials · 2026Article
- A dual-adjuvanted HA stem nanoparticle vaccine elicits a multifunctional antibody response that is associated with protection in newborn monkeys.Cell reports. Medicine · 2026Article
- IL-1 delineates squalene-based adjuvant efficacy and reactogenicity in a cell-type-specific manner.NPJ vaccines · 2026Article
- Skeletal muscle as a dynamic immunological niche for vaccination.Frontiers in immunology · 2026Review
- Spatial transcriptomic mapping of early immune responses to an adjuvanted recombinant hemagglutinin vaccine.Frontiers in immunology · 2026Article
- Age-related changes in the immune system and challenges for the development of age-specific vaccines.Annals of medicine · 2025Review
- Comparison of Adjuvant Potency of Alum, AddaVax, and ISA 71 VG on the Seasonal Split Influenza Vaccine in Mice.Microorganisms · 2025Article
- Precision Adjuvant Strategies in Vaccine Development for Substance Use Disorders: Variability and Mechanistic Insights.Pharmaceutics · 2025Review
- Modular assembly and immunological evaluation of a promising bioconjugate nanovaccine against Klebsiella pneumoniae O2 serotype.NPJ vaccines · 2025Article
- A High-Yield Recombinant Inactivated Whole-Virion Nasal Influenza A(H1N1)pdm09 Virus Vaccine with an Attenuated PB2 Gene.International journal of molecular sciences · 2025Article
- Emulsion adjuvant-induced uric acid release modulates optimal immunogenicity by targeting dendritic cells and B cells.NPJ vaccines · 2025Article
- Linking vaccine adjuvant mechanisms of action to function.Science immunology · 2025Review
- Combination adjuvant improves influenza virus immunity by downregulation of immune homeostasis genes in lymphocytes.ImmunoHorizons · 2025Article
- The recent advances in vaccine adjuvants.Frontiers in immunology · 2025Review
- The role of cell death pathways in respiratory viral infection and vaccination: two sides of the same coin.Frontiers in immunology · 2025Review
33 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
13 authors at 5 institutions in 2 countries.
Funding
Abstract
Vaccines are the most effective agents to control infections. In addition to the pathogen antigens, vaccines contain adjuvants that are used to enhance protective immune responses. However, the molecular mechanism of action of most adjuvants is ill-known, and a better understanding of adjuvanticity is needed to develop improved adjuvants based on molecular targets that further enhance vaccine efficacy. This is particularly important for tuberculosis, malaria, AIDS, and other diseases for which protective vaccines do not exist. Release of endogenous danger signals has been linked to adjuvanticity; however, the role of extracellular ATP during vaccination has never been explored. Here, we tested whether ATP release is involved in the immune boosting effect of four common adjuvants: aluminum hydroxide, calcium phosphate, incomplete Freund's adjuvant, and the oil-in-water emulsion MF59. We found that intramuscular injection is always associated with a weak transient release of ATP, which was greatly enhanced by the presence of MF59 but not by all other adjuvants tested. Local injection of apyrase, an ATP-hydrolyzing enzyme, inhibited cell recruitment in the muscle induced by MF59 but not by alum or incomplete Freund's adjuvant. In addition, apyrase strongly inhibited influenza-specific T-cell responses and hemagglutination inhibition titers in response to an MF59-adjuvanted trivalent influenza vaccine. These data demonstrate that a transient ATP release is required for innate and adaptive immune responses induced by MF59 and link extracellular ATP with an enhanced response to vaccination.
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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.