Postdoctoral Fellow Stanford Univ. Stanford, California, United States
Disclosure(s):
Okikiola Olajide, PhD: No financial relationships to disclose
Introduction/Rationale: Human spleen organoids represent a promising ex vivo model that recapitulates the cellular diversity, spatial architecture, and immune functionality of secondary lymphoid tissues. These organoids offer a human-relevant platform for preclinical vaccine evaluation, potentially improving translational insight into immunogenicity. While recent studies have demonstrated antigen-specific immune responses to live-attenuated vaccines in spleen organoids, it remains unclear whether such responses extend to subunit-based immunogens, which form the basis of many modern vaccines. To address this, we evaluated the ability of spleen organoids to generate antibody responses to protein subunit immunogens.
Methods: Organoids were stimulated with wild-type SARS-CoV-2 spike and receptor-binding domain (RBD) proteins multimerized on mi3 nanoparticles, both with and without adjuvant formulations. Antigen-specific B cell activation was monitored by flow cytometry and ELISA, and antibody maturation was evaluated through single B cell sorting and sequencing.
Results: Consistent with waning immune memory observed in post-pandemic human populations, baseline responses to wild-type immunogens were modest. However, booster formulations and adjuvanted constructs enhanced antigen-specific responses, highlighting the platform’s sensitivity to immunogen design and immune memory dynamics.
Conclusion: Together, these results suggest that human spleen organoids can model both the baseline and augmented humoral responses to protein subunit vaccines, underscoring their potential as a human-derived platform for preclinical vaccine testing and immune response modeling.
