Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Nanoparticle-Based Secretory Granules Induce a Specific and Long-Lasting Immune Response through Prolonged Antigen Release

Version 1 : Received: 29 January 2024 / Approved: 30 January 2024 / Online: 30 January 2024 (05:30:55 CET)

A peer-reviewed article of this Preprint also exists.

Bosch-Camós, L.; Martínez-Torró, C.; López-Laguna, H.; Lascorz, J.; Argilaguet, J.; Villaverde, A.; Rodríguez, F.; Vázquez, E. Nanoparticle-Based Secretory Granules Induce a Specific and Long-Lasting Immune Response through Prolonged Antigen Release. Nanomaterials 2024, 14, 435. Bosch-Camós, L.; Martínez-Torró, C.; López-Laguna, H.; Lascorz, J.; Argilaguet, J.; Villaverde, A.; Rodríguez, F.; Vázquez, E. Nanoparticle-Based Secretory Granules Induce a Specific and Long-Lasting Immune Response through Prolonged Antigen Release. Nanomaterials 2024, 14, 435.

Abstract

Developing prolonged antigen delivery systems that mimick the long-term exposure to pathogens appears as a promising, still poorly explored approach to reach durable immunities. In this study, we have used a simple technology by which his-tagged proteins can be assembled, assisted by divalent cations, as supramolecular complexes with progressive complexity, namely protein-only nanoparticles and microparticles. Microparticles produced out of nanoparticles are biomimetics of secretory granules from the mammalian hormonal system. Upon subcutaneous administration, they slowly disintegrate, acting as an endocrine-like secretory system, and rendering the building block nanoparticles progressively bioavailable. The performance of such materials, previously validated for drug delivery in oncology, has been tested here regarding the potential for time-prolonged antigen release. This has been done by taking, as building blocks, a nanostructured version of p30, a main structural immunogen from the African swine fever virus (ASFV). By challenging the system in both mice and pigs, we have observed unusually potent pro-inflammatory activity in porcine macrophages, and long-lasting humoral and cellular responses in vivo, which might overcome the need for an adjuvant. The robustness of both innate and adaptive responses tag, for the first time, these dynamic depot materials as a novel and valuable instrument with transversal applicability in immune stimulation and vaccinology.

Keywords

Recombinant proteins; Biomaterials; protein nanoparticles; secretory granules; immunization

Subject

Biology and Life Sciences, Biology and Biotechnology

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