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

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Detalles Bibliográficos
Publicado en:	Vaccines vol. 13, no. 11 (2025), p. 1146-1162
Autor principal:	Hernandez-Franco, Juan F
Otros Autores:	Gude Sushma, Morrison, Rachel A, Castillo Perez Daniela, Voytik-Harbin, Sherry L, HogenEsch Harm
Publicado:	MDPI AG
Materias:	Indianapolis Indiana United States > US Collagen Vaccines Adjuvants Immunity Immune system Lymphocytes T Phenotypes Aluminum Antigen presentation Antibody response Antigens Lymph nodes Localization Laboratory animals Bone marrow Lymphocytes Oligomers Immune clearance Injection Immune response Lymphatic system Immunoglobulin G Collagen (type I) Lymphocytes B Enzymes Ovalbumin Biocompatibility Antibodies Germinal centers Humoral immunity Safety CD4 antigen Antigen-presenting cells Oligonucleotides Vaccine efficacy Immunity (Disease) Self-assembly Immune response (humoral) Durability Immunological tolerance Dendritic cells Retention Scaffolds Immunization Social
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Descripción
Resumen:	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.
ISSN:	2076-393X
DOI:	10.3390/vaccines13111146
Fuente:	Biological Science Database