Structural analysis of adjuvant-coupled antigens is important for rational vaccine development but has been impeded by the lack of appropriate techniques. In principle, depending on the mobility of the antigen site, solution NMR or magic-angle spinning (MAS) solid-state NMR is pertinent to the study of such dynamic and heterogeneous systems. However, their application has been hampered by the relatively low antigen content in vaccine formulations. We show that isotope labelling together with sensitivity enhancement techniques allow to overcome the penalty associated with the antigen dilution [1]. This makes it possible to assess the structure of antigens, both in their free, unformulated form and once chemically coupled or genetically fused to the surface of large virus-like particles (VLPs). Comparison of the NMR fingerprints between the free and VLP-coupled forms of the antigen provides site-specific information of the structural change or conservation occurring upon bioconjugation. This work demonstrates that NMR can play a major role in vaccine design, formulation studies, and manufacturing process development.