In-Situ Self-Assembling Oligomeric Collagen Scaffold Enhances Vaccine Retention and Vaccine-Induced Humoral Immunity

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出版年:Vaccines vol. 13, no. 11 (2025), p. 1146-1162
第一著者: Hernandez-Franco, Juan F
その他の著者: Gude Sushma, Morrison, Rachel A, Castillo Perez Daniela, Voytik-Harbin, Sherry L, HogenEsch Harm
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MDPI AG
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022 |a 2076-393X 
024 7 |a 10.3390/vaccines13111146  |2 doi 
035 |a 3275574072 
045 2 |b d20250101  |b d20251231 
084 |a 231639  |2 nlm 
100 1 |a Hernandez-Franco, Juan F  |u Department of Comparative Pathobiology, College of Veterinary Medicine, Purdue University, West Lafayette, IN 47907, USA; jfhernan@purdue.edu (J.F.H.-F.); casti134@purdue.edu (D.C.P.) 
245 1 |a In-Situ Self-Assembling Oligomeric Collagen Scaffold Enhances Vaccine Retention and Vaccine-Induced Humoral Immunity 
260 |b MDPI AG  |c 2025 
513 |a Journal Article 
520 3 |a Background/Objectives: Subunit vaccines composed of purified proteins and adjuvants offer excellent safety, but often generate short-lived immunity due to rapid antigen clearance and limited antigen-presenting cell engagement. Sustained, localized delivery of antigen and adjuvant may improve the magnitude and durability of the immune response without compromising safety. This study evaluated an in-situ polymerizing type I oligomeric collagen (Oligomer) scaffold to localize antigen/adjuvant at the injection site and prolong antigen presentation. Methods: Mice were immunized intramuscularly with ovalbumin (OVA) and CpG oligonucleotide adjuvant delivered alone or co-formulated with Oligomer. Antibody response and inflammation at the injection site were assessed post-booster at early (Day 32) and late (Day 68) time points. Antigen retention and dendritic cell trafficking to draining lymph nodes were evaluated using fluorescently labeled OVA. Results: The Oligomer scaffold retained vaccine antigen at the injection site without eliciting a material-mediated foreign body response. Co-delivery of OVA and CpG within the scaffold enhanced germinal center activity, increased follicular helper T cells and germinal center B cells, and skewed CD4+ T cells toward a Th1 phenotype. Humoral responses were greater and more durable, with higher OVA-specific IgG, IgG1, and IgG2a titers and an increased number of bone marrow antibody-secreting cells persisting through Day 68. Antigen-positive dendritic cells, including both resident and migratory subsets, were elevated in draining lymph nodes, indicating enhanced antigen transport. No anti-mouse collagen I antibodies were detected, confirming the maintenance of collagen self-tolerance. Conclusions: The Oligomer delivery platform functioned as a localized, immunotolerant vaccine depot, sustaining antigen availability and immune cell engagement. This spatiotemporal control enhanced germinal center responses and generated a more robust, durable humoral immune response, supporting its potential to improve subunit vaccine efficacy while maintaining an excellent safety profile. 
651 4 |a Indianapolis Indiana 
651 4 |a United States--US 
653 |a Collagen 
653 |a Vaccines 
653 |a Adjuvants 
653 |a Immunity 
653 |a Immune system 
653 |a Lymphocytes T 
653 |a Phenotypes 
653 |a Aluminum 
653 |a Antigen presentation 
653 |a Antibody response 
653 |a Antigens 
653 |a Lymph nodes 
653 |a Localization 
653 |a Laboratory animals 
653 |a Bone marrow 
653 |a Lymphocytes 
653 |a Oligomers 
653 |a Immune clearance 
653 |a Injection 
653 |a Immune response 
653 |a Lymphatic system 
653 |a Immunoglobulin G 
653 |a Collagen (type I) 
653 |a Lymphocytes B 
653 |a Enzymes 
653 |a Ovalbumin 
653 |a Biocompatibility 
653 |a Antibodies 
653 |a Germinal centers 
653 |a Humoral immunity 
653 |a Safety 
653 |a CD4 antigen 
653 |a Antigen-presenting cells 
653 |a Oligonucleotides 
653 |a Vaccine efficacy 
653 |a Immunity (Disease) 
653 |a Self-assembly 
653 |a Immune response (humoral) 
653 |a Durability 
653 |a Immunological tolerance 
653 |a Dendritic cells 
653 |a Retention 
653 |a Scaffolds 
653 |a Immunization 
653 |a Social 
700 1 |a Gude Sushma  |u Weldon School of Biomedical Engineering, Purdue University, West Lafayette, IN 47907, USA; sgude@purdue.edu (S.G.); morri107@purdue.edu (R.A.M.) 
700 1 |a Morrison, Rachel A  |u Weldon School of Biomedical Engineering, Purdue University, West Lafayette, IN 47907, USA; sgude@purdue.edu (S.G.); morri107@purdue.edu (R.A.M.) 
700 1 |a Castillo Perez Daniela  |u Department of Comparative Pathobiology, College of Veterinary Medicine, Purdue University, West Lafayette, IN 47907, USA; jfhernan@purdue.edu (J.F.H.-F.); casti134@purdue.edu (D.C.P.) 
700 1 |a Voytik-Harbin, Sherry L  |u Weldon School of Biomedical Engineering, Purdue University, West Lafayette, IN 47907, USA; sgude@purdue.edu (S.G.); morri107@purdue.edu (R.A.M.) 
700 1 |a HogenEsch Harm  |u Department of Comparative Pathobiology, College of Veterinary Medicine, Purdue University, West Lafayette, IN 47907, USA; jfhernan@purdue.edu (J.F.H.-F.); casti134@purdue.edu (D.C.P.) 
773 0 |t Vaccines  |g vol. 13, no. 11 (2025), p. 1146-1162 
786 0 |d ProQuest  |t Biological Science Database 
856 4 1 |3 Citation/Abstract  |u https://www.proquest.com/docview/3275574072/abstract/embedded/7BTGNMKEMPT1V9Z2?source=fedsrch 
856 4 0 |3 Full Text + Graphics  |u https://www.proquest.com/docview/3275574072/fulltextwithgraphics/embedded/7BTGNMKEMPT1V9Z2?source=fedsrch 
856 4 0 |3 Full Text - PDF  |u https://www.proquest.com/docview/3275574072/fulltextPDF/embedded/7BTGNMKEMPT1V9Z2?source=fedsrch