Intranasal Epitope‐Polymer Vaccine Lodges Resident Memory T Cells Protecting Against Influenza Virus
Ziyang Liu, Md. Tanvir Kabir, Shuxiong Chen, Heran Zhang, Linda M. Wakim, Bernd H. A. Rehm
Abstract
Abstract Intranasal vaccines, unlike injectable vaccines, boost immunity along the respiratory tract; this can significantly limit respiratory virus replication and shedding. There remains a need to develop mucosal adjuvants and vaccine delivery systems that are both safe and effective following intranasal administration. Here, biopolymer particles (BP) densely coated with repeats of MHC class I restricted immunodominant epitopes derived from influenza A virus namely NP 366 , a nucleoprotein‐derived epitope and PA 224 , a polymerase acidic subunit derived epitope, are bioengineered. These BP‐NP 366 /PA 224 can be manufactured at a high yield and are obtained at ≈93% purity, exhibiting ambient‐temperature stability. Immunological characterization includes comparing systemic and mucosal immune responses mounted following intramuscular or intranasal immunization. Immunization with BP‐NP 366 /PA 224 without adjuvant triggers influenza‐specific CD8 + T cell priming and memory CD8 + T cell development. Co‐delivery with the adjuvant poly(I:C) significantly boosts the size and functionality of the influenza‐specific pulmonary resident memory CD8 + T cell pool. Intranasal, but not intramuscular delivery of BP‐NP 366 /PA 224 with poly(I:C), provides protection against influenza virus challenge. Overall, the BP approach demonstrates as a suitable antigen formulation for intranasal delivery toward induction of systemic protective T cell responses against influenza virus.