Development of a single-dose Q fever vaccine with an injectable nanoparticle-loaded hydrogel: effect of sustained co-delivery of antigen and adjuvant.

Publisher: Taylor & Francis Country of Publication: England NLM ID: 9417471 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1521-0464 (Electronic) Linking ISSN: 10717544 NLM ISO Abbreviation: Drug Deliv Subsets: MEDLINE

Publication: 2015->: Abingdon, Oxford : Taylor & Francis
Original Publication: Orlando, FL : Academic Press, c1993-

Nanoparticles*/chemistry ; Nanoparticles*/administration & dosage ; Hydrogels*/chemistry ; Hydrogels*/administration & dosage ; Adjuvants, Immunologic*/administration & dosage ; Adjuvants, Immunologic*/chemistry ; Bacterial Vaccines*/administration & dosage ; Bacterial Vaccines*/immunology ; Q Fever*/prevention & control ; Q Fever*/immunology ; Antigens, Bacterial*/immunology ; Antigens, Bacterial*/administration & dosage; Coxiella burnetii/immunology ; Immunoglobulin G/immunology ; Adjuvants, Vaccine/administration & dosage ; Adjuvants, Vaccine/chemistry ; Animals ; Mice ; Female ; Delayed-Action Preparations ; Polylactic Acid-Polyglycolic Acid Copolymer ; Mice, Inbred BALB C

Q fever is a zoonotic infectious disease caused by Coxiella burnetii, and there is currently no FDA-approved vaccine for human use. The whole-cell inactivated vaccine Q-VAX, which is only licensed in Australia, has a risk of causing severe adverse reactions, making subunit vaccines a good alternative. However, most subunit antigens are weak immunogens and require two or more immunizations to elicit an adequate level of immunity. We hypothesized that by combining a nanoparticle to co-deliver both a protein antigen and an adjuvant, together with a hydrogel depot for sustained-release kinetics, a single-administration of a nanoparticle-loaded hydrogel vaccine could elicit a strong and durable immune response. We synthesized and characterized a protein nanoparticle (CBU-CpG-E2) that co-delivered the immunodominant protein antigen CBU1910 (CBU) from C. burnetii and the adjuvant CpG1826 (CpG). For sustained release, we examined different mixtures of PLGA-PEG-PLGA (PPP) polymers and identified a PPP solution that was injectable at room temperature, formed a hydrogel at physiological temperature, and continuously released protein for 8 weeks in vivo. Single-dose vaccine formulations were administered to mice, and IgG, IgG1, and IgG2c levels were determined over time. The vaccine combining both the CBU-CpG-E2 nanoparticles and the PPP hydrogel elicited a stronger and more durable humoral immune response than the soluble bolus nanoparticle vaccines (without hydrogel) and the free antigen and free adjuvant-loaded hydrogel vaccines (without nanoparticles), and it yielded a balanced IgG2c/IgG1 response. This study demonstrates the potential advantages of using this modular PPP hydrogel/nanoparticle system to elicit improved immune responses against infectious pathogens.

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R01 EB027797 United States EB NIBIB NIH HHS; R21 AI175980 United States AI NIAID NIH HHS

Keywords: Nanoparticle vaccine; Q fever; co-delivery; hydrogel; sustained delivery

0 (Hydrogels)
0 (Adjuvants, Immunologic)
0 (Bacterial Vaccines)
0 (Delayed-Action Preparations)
0 (Antigens, Bacterial)
1SIA8062RS (Polylactic Acid-Polyglycolic Acid Copolymer)
0 (Immunoglobulin G)
0 (Adjuvants, Vaccine)

Date Created: 20250502 Date Completed: 20250502 Latest Revision: 20260306

20260306

PMC12051587

10.1080/10717544.2025.2476144

40314164