Although vaccination is historically one of the most successful strategies for the prevention of infectious diseases, development of vaccines for cancer and many chronic infections, such as HIV, malaria, and tuberculosis, has remained a challenge. Strong and long-lasting antigen-specific T cell responses are critical for therapy of these diseases. A major challenge in achieving a robust CD8+ T cell response is the requirement of spatio-temporal orchestration of antigen cross-presentation in antigen-presenting cells with innate stimulation. Here, we discuss the development of nanoparticle vaccine (nanovaccine) that modulates the innate immune system and enhances adaptive immunity with reduced toxicity. We address how nanovaccines can integrate multiple functions, such as lymph node targeting, antigen presentation, and stimulation of innate immunity, to achieve a robust T cell response for immunotherapy.

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Objectives: Eosinophilic esophagitis (EoE), the most common eosinophilic gastrointestinal disease (EGID), is associated with lamina propria (LP) fibrosis. The relationship of EoE to other EGIDs is still unclear. We frequently observe cases of concurrent esophageal eosinophilia and extra-esophageal mucosal eosinophilia. The purpose of this study was to compare clinical, endoscopic, and histologic features, as well as the prevalence of esophageal LP fibrosis in children with EGID and concurrent esophageal eosinophilia to children with EoE. We also examine the current practices of pathologists in evaluating fibrosis. Methods: We reviewed esophageal biopsies from index cases of EoE (N = 38), EGID with significant esophageal eosinophilia (≥15 eos/hpf) (EGID-SEE, N = 38), EGID with mild esophageal eosinophilia (1–14 eos/hpf) (EGID-MEE, N = 12), and EGID with no esophageal eosinophilia (EGID-NEE, N = 12) for LP presence, adequacy, and fibrosis. Results: EoE and EGID-SEE cases share similar demographics, esophageal endoscopic features, and symptoms. A majority of EGID-SEE cases (71%) had adequate LP for the evaluation of fibrosis, similar to EoE cases (87%). The prevalence of esophageal fibrosis in EoE (79%) and EGID-SEE (55%) cases were similar, whereas no fibrosis was detected in the EGID-MEE and EGID-NEE cases. The fibrosis was patchy and often detected in the distal esophagus. Fourteen cases were reclassified from their original clinical diagnosis as having fibrosis by the study pathologists. Conclusions: Cases of EGID-SEE have overlapping features with EoE, suggesting that all EGIDs are part of a disease continuum. A consensus for the evaluation of LP fibrosis is needed.

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