表位
鼻腔给药
病毒学
佐剂
病毒
流感疫苗
免疫系统
甲型流感病毒
医学
T细胞
免疫学
免疫原性
抗原
生物
作者
Ziyang Liu,Md. Tanvir Kabir,Shuxiong Chen,Huixue Zhang,Linda M. Wakim,Bernd H. A. Rehm
标识
DOI:10.1002/adhm.202304188
摘要
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 NP 366 , a nucleoprotein‐derived epitope and PA 224 , a polymerase acidic subunit derived epitope. These BP‐NP 366 /PA 224 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‐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. This article is protected by copyright. All rights reserved
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