Abstract
Aluminum-based adjuvants are widely used in vaccine formulations due to their immunostimulatory properties and strong safety profile. Despite their effectiveness and safety, the exact mechanisms by which they enhance vaccine efficacy remain unclear. One proposed mechanism is that aluminum adjuvants form a depot that gradually releases antigens, thereby improving antigen uptake by antigen-presenting cells. This study investigates the porous structures of two commonly used aluminum adjuvants, aluminum hydroxide (AH) and aluminum phosphate (AP), using small-angle X-ray scattering (SAXS) and small-angle neutron scattering (SANS). Our measurements reveal that AH nanoparticles, with their needle-like morphology, form smaller, interconnected pores within the aggregated architecture. In contrast, AP nanoparticles, with a plate-like shape, form more discrete, isolated porous structures. Both adjuvants have pore sizes within the range of commonly used vaccine antigens, supporting the depot theory. Our findings also reveal that antigen retention is prolonged when the antigen size is comparable to the average pore size of the adjuvant. This study highlights the utility of SAXS and SANS for in-situ characterization of adjuvant porosity and provides insights into how nanoparticle morphology affects antigen retention and release. By elucidating these structural details, our research underscores the importance of porous structure in adjuvant function and offers potential pathways for improving vaccine formulations through tailored adjuvant design.
| Original language | English |
|---|---|
| Article number | 126813 |
| Journal | Vaccine |
| Volume | 50 |
| DOIs | |
| State | Published - Mar 19 2025 |
Funding
This work is supported by Grant No. 2022-67022-38145 from the USDA National Institute of Food and Agriculture. This work is based on research conducted at the Center for High-Energy X-ray Sciences (CHEXS), which is supported by the National Science Foundation (BIO, ENG and MPS Directorates) under award DMR-2342336, and the Macromolecular Diffraction at CHESS (MacCHESS) facility, which is supported by award 1-P30-GM124166 from the National Institute of General Medical Sciences and the National Institutes of Health. SANS measurements were performed using the Bio-SANS instrument of the Center for Structural Molecular Biology (FWP ERKP291), a Structural Biology Resource of the U.S. DOE Office of Biological and Environment Research. This research used resources at the High Flux Isotope Reactor, a U. S. DOE Basic Energy Sciences User Facility operated by the Oak Ridge National Laboratory (ORNL). This manuscript has been authored by UT-Battelle, LLC, under Contract No. DE-AC05-00OR22725 with the U.S. Department of Energy. The United States Government retains and the publisher, by accepting the article for publication, acknowledges that the United States Government retains a non-exclusive, paid-up, irrevocable, world-wide license to publish or reproduce the published form of this manuscript, or allow others to do so, for United States Government purposes. The Department of Energy will provide public access to these results of federally sponsored research in accordance with the DOE Public Access Plan (http://energy.gov/downloads/doe-public-access-plan). This work is based on research conducted at the Center for High-Energy X-ray Sciences (CHEXS), which is supported by the National Science Foundation (BIO, ENG and MPS Directorates) under award DMR-1829070., and the Macromolecular Diffraction at CHESS (MacCHESS) facility, which is supported by award 1-P30-GM124166-01A1 from the National Institute of General Medical Sciences, National Institutes of Health, and by New York State's Empire State Development Corporation (NYSTAR). SANS measurements were performed using the Bio-SANS instrument of the Center for Structural Molecular Biology (FWP ERKP291), a Structural Biology Resource of the U.S. DOE Office of Biological and Environment Research. This research used resources at the High Flux Isotope Reactor, a U. S. DOE Basic Energy Sciences User Facility operated by the Oak Ridge National Laboratory (ORNL). This manuscript has been authored by UT-Battelle, LLC, under Contract No. DE-AC05-00OR22725 with the U.S. Department of Energy. The United States Government retains and the publisher, by accepting the article for publication, acknowledges that the United States Government retains a non-exclusive, paid-up, irrevocable, world-wide license to publish or reproduce the published form of this manuscript, or allow others to do so, for United States Government purposes. The Department of Energy will provide public access to these results of federally sponsored research in accordance with the DOE Public Access Plan ( http://energy.gov/downloads/doe-public-access-plan ).
Keywords
- Aluminum adjuvant
- Antigen depot formation
- Antigen retention
- Arrangement of the pores
- Average pore size
- Small-angle X-ray scattering
- Small-angle neutron scattering
- Vaccine formulation