Nasal immunization with RSV F and G protein fragments conjugated to an M cell-targeting ligand induces an enhanced immune response and protection against RSV infection

Abstract

Human respiratory syncytial virus (RSV) is a major paediatric health concern worldwide. The development of an effective and safe vaccine against RSV is urgently needed. As RSV infects via the mucosal surfaces, developing a nasal vaccine may offer protective benefits over alternative administration routes. In this study, we tested a recombinant protein FG-Gb1 as an intranasal vaccine candidate against RSV. FG-Gb1 consists of the core fragments of the RSV fusion (F) and attachment (G) proteins conjugated to an microfold (M) cell-specific ligand Gb-1. Intranasal immunization with FG-Gb1 induced efficient systemic and mucosal immune responses as measured by the level of antigen-specific antibodies, cytokine-secreting cells and antigen-specific lymphocyte proliferation after exposure to antigen. Moreover, intranasal immunization induced protective immunity against nasal challenge with RSV, which was confirmed by a lack of weight loss and by viral clearance after challenge. Collectively, we confirmed that a ligand capable of targeting the conjugated antigen to nasopharynx-associated lymphoid tissue (NALT) can be used as an effective nasal vaccine adjuvant to induce protective immunity against RSV infection. Moreover, FG-Gb1 may have promise as an RSV vaccine but requires further studies.