Incorporating the Host-Derived Immunostimulant CPDI-02 by Separate Encapsulation, Co-Encapsulation, or Surface Modification Differentially Affects Induction of Humoral Immunity Against Microparticle-Encapsulated Protein Antigen in Naïve C57BL/6 Mice After Intranasal Immunization
Year: 2026
Type: preprint
Abstract: Encapsulating protein subunit vaccines in biodegradable microparticles (MP) can increase induction of long-term protective mucosal and systemic antibodies after respiratory administration but requires incorporation of a mucosal immunostimulant. We previously found that incorporating complement peptide-derived immunostimulant-02 (CPDI-02) with MP-encapsulated LPS-free OVA through surface modification of the same ~1 µm PLGA 50:50 MP greatly increases mucosal and systemic OVA-specific antibodies in young, naïve female C57BL/6 mice at 14 and 90 days post-intranasal administration. Here, we directly compared effects of incorporating CPDI-02 or inactive scCPDI-02 with MP-encapsulated LPS-free OVA by separate encapsulation (SE), co-encapsulation (CE), or surface modification (SM) on induction of OVA-specific IgA, IgM, and IgG antibody secreting cells (ASCs) in the lungs and spleen, IgA antibodies in nasal lavage fluid, IgA and IgG antibodies in bronchoalveolar lavage fluid, and IgG subclasses in the serum at 14 days post-intranasal administration. We found that SE incorporation induced greater or similar levels of mucosal and systemic OVA-specific ASCs and mucosal IgA and IgG titers but greater titers of systemic IgG subclasses than CE or SM incorporation versus inactive scCPDI-02. Thus, given that surface modification with CPDI-02 induces high titers of OVA-specific systemic and mucosal antibodies at 14 and 90 days post-intranasal immunization under the same experimental conditions, separate encapsulation of CPDI-02 is expected to more broadly induce long-term mucosal and systemic antibodies against MP-encapsulated protein vaccines than co-encapsulation and surface modification after intranasal and possibly other routes of mucosal immunization.
Source: Preprints.org
Language: English
Subfield: Pharmaceutical Science
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W7171417580