Intranasal Vaccination With Recombinant Antigen-FLIPr Fusion Protein Alone Induces Long-Lasting Systemic Antibody Responses and Broad T Cell Responses

• Published in: Frontiers in immunology Vol. 12; p. 751883
• Main Authors: Hsieh, Ming-Shu, Hsu, Chia-Wei, Tu, Ling-Ling, Chai, Kit Man, Yu, Li-Lu, Wu, Chiao-Chieh, Chen, Mei-Yu, Chiang, Chen-Yi, Liu, Shih-Jen, Liao, Ching-Len, Chen, Hsin-Wei
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Media S.A 11.10.2021
• Subjects: Administration, Intranasal; Animals; Antigens - administration & dosage; Bacterial Proteins - administration & dosage; CD4-Positive T-Lymphocytes - drug effects; CD4-Positive T-Lymphocytes - immunology; CD8-Positive T-Lymphocytes - drug effects; CD8-Positive T-Lymphocytes - immunology; Dendritic Cells - drug effects; Dendritic Cells - immunology; Fcγ receptor; formyl peptide receptor-like 1 inhibitory protein (FLIPr); Immunity, Mucosal; Immunoglobulin A - blood; Immunoglobulin G - blood; Immunology; intranasal vaccination; Mice; Mice, Inbred C57BL; mucosal vaccines; Ovalbumin - administration & dosage; Recombinant Fusion Proteins - administration & dosage; Vaccination - methods; Zika vaccines; Fcγ receptor; formyl peptide receptor-like 1 inhibitory protein (FLIPr); Zika vaccines; intranasal vaccination; mucosal vaccines
• ISSN: 1664-3224; 1664-3224
• DOI: 10.3389/fimmu.2021.751883

A simple formulation is urgently needed for mucosal vaccine development. We employed formyl peptide receptor-like 1 inhibitory protein (FLIPr), an FcγR antagonist secreted by , as a vector to target ovalbumin (OVA) to dendritic cells (DCs) intranasal administration. Our results demonstrate that intranasal administration of recombinant OVA-FLIPr fusion protein (rOVA-FLIPr) alone efficiently delivers OVA to DCs in nasal lymphoid tissue. Subsequently, OVA-specific IgG and IgA antibodies in the circulatory system and IgA antibodies in mucosal tissue were detected. Importantly, activation of OVA-specific CD4 and CD8 T cells and induction of a broad-spectrum cytokine secretion profile were detected after intranasal administration of rOVA-FLIPr alone in immunocompetent C57BL/6 mice. Furthermore, we employed immunodeficient AG129 mice as a Zika virus infection model and demonstrated that intranasal administration of recombinant Zika virus envelope protein domain III-FLIPr fusion protein induced protective immune responses against the Zika virus. These results suggest that antigen-FLIPr fusion protein alone intranasal administration can be applied to mucosal vaccine development.