Intranasal Epitope‐Polymer Vaccine Lodges Resident Memory T Cells Protecting Against Influenza Virus

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, we have bioengineered biopolymer particles (BP) densely coated with repeats of MHC class I restricted immunodominant epitopes derived from influenza A virus namely NP366, a nucleoprotein‐derived epitope and PA224, a polymerase acidic subunit derived epitope. These BP‐NP366/PA224 could be manufactured at high yield and are obtained at ∼93% purity exhibiting ambient‐temperature stability. Immunological characterisation includes comparing systemic and mucosal immune responses mounted following intramuscular or intranasal immunisation. Immunization with BP‐NP366/PA224 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‐NP366/PA224 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.This article is protected by copyright. All rights reserved