Respiratory viruses that infect and replicate to high levels in the upper airway are highly transmissible from person to person. Additionally, there are large families of pre-emergent viruses circulating among wild animal populations that can replicate in human airway cells and therefore have high pandemic potential risk^1,2. Despite the vast pandemic potential of these respiratory viruses, most vaccines that combat respiratory viruses are given intramuscularly. Intramuscular vaccines protect against severe lower airway disease but do not necessarily protect against upper airway viral replication and transmission.

A major goal of respiratory mucosal vaccines is to elicit a local, rapid and effective immune response at the site of entry for respiratory viruses that infect the upper airway. Respiratory mucosal vaccines should enable the production of antibody-secreting plasma cells, which generate secretory IgA antibodies, and tissue-resident memory B and T cells to counteract viruses that replicate in the upper airway. These vaccines could therefore substantially reduce the transmission of both endemic and emerging respiratory viruses^3,4. Given that there is currently only one licensed respiratory mucosally delivered vaccine against influenza A and B, FluMist⁵, there is much room to improve. FluMist is a live-attenuated vaccine against influenza A and B that must replicate in the respiratory mucosa to generate an effective immune response; given this requirement, pre-existing immunity is thought to inhibit FluMist replication and therefore reduce vaccine efficacy. FluMist was recently approved for in-home use via self-administration. Despite this major milestone, there are antigenic and genetic mismatch issues with vaccine and circulating strains that negatively affect vaccine efficacy.

在上气道感染并大量复制的呼吸道病毒在人与人之间具有高度传播性。此外，在野生动物种群中传播的大量出苗前病毒可以在人类气道细胞中复制，因此具有很高的大流行潜在风险 ^1,2 。尽管这些呼吸道病毒具有巨大的大流行潜力，但大多数对抗呼吸道病毒的疫苗都是通过肌肉注射接种的。肌内注射疫苗可以预防严重的下气道疾病，但不一定能防止上气道病毒的复制和传播。

呼吸道粘膜疫苗的一个主要目标是在感染上呼吸道的呼吸道病毒进入部位引发局部、快速和有效的免疫反应。呼吸道粘膜疫苗应能够产生分泌抗体的浆细胞，从而产生分泌型 IgA 抗体，以及组织驻留记忆 B 细胞和 T 细胞，以抵消在上气道中复制的病毒。因此，这些疫苗可以大大减少地方性和新出现的呼吸道病毒的传播 ^3,4 。鉴于目前只有一种获得许可的针对甲型和乙型流感的呼吸道粘膜递送疫苗，即 FluMist ⁵ ，还有很大的改进空间。FluMist 是一种针对甲型和乙型流感的减毒活疫苗，必须在呼吸道粘膜中复制才能产生有效的免疫反应;鉴于这一要求，预先存在的免疫力被认为会抑制 FluMist 复制，从而降低疫苗效力。FluMist 最近被批准通过自我管理在家中使用。尽管有这一重要里程碑，但疫苗和循环毒株仍存在抗原和遗传错配问题，对疫苗疗效产生负面影响。