Functional Immunonutraceutical Supplementation Enhances Humoral and Innate Immune Dynamics in a Controlled Immune-Challenge Rabbit Model

Background/Objectives: Immunonutrition uses dietary bioactive compounds to support immune function while preserving systemic physiological balance. Donkey milk, bovine colostrum, and royal jelly contain complementary antimicrobial, immunoglobulin-rich, and immunoregulatory components, but their combined effects remain insufficiently characterized. Methods: A 6-week controlled study was conducted in female rabbits assigned to four groups (n = 15/group): vaccinated only (G1), immunonutraceutical only (G2), vaccination plus immunonutraceutical (G3), and pre-conditioned immunonutraceutical followed by vaccination and continued supplementation (G4). Serum total immunoglobulins and lysozyme were measured longitudinally. Biochemical indices were monitored throughout the study, and hematological parameters were evaluated at the final time point. Mixed-effects models, generalized estimating equations, principal component analysis, and correlation-based systems analyses were applied. Results: Supplementation significantly modulated both humoral and innate immune responses. The strongest terminal immunoglobulin response was observed in G4 (26.00 ± 5.80 mg/mL), whereas sustained lysozyme elevation was most pronounced in supplemented groups, particularly G3 (3.13 ± 0.44 ng/mL). Within-subject analysis demonstrated significant innate–adaptive immune coherence (p = 0.000006). Biochemical analyses showed coordinated metabolic adaptation without evidence of organ toxicity, and hematological findings indicated preserved inflammatory and hematopoietic stability. Conclusions: Multi-component immunonutraceutical supplementation enhanced humoral and innate immune dynamics in a timing-dependent manner while maintaining biochemical and hematological safety. These findings support the potential of combined donkey milk, bovine colostrum, and royal jelly as functional ingredients for coordinated immune support.