Center for Vaccine Research, Statens Serum Institut, Copenhagen, Denmark.
Virus Research & Development Laboratory, Department of Virology and Microbiological Special diagnostics, Statens Serum Institut, Copenhagen, Denmark.
EBioMedicine. 2022 Oct;84:104248. doi: 10.1016/j.ebiom.2022.104248. Epub 2022 Sep 7.
Licensed vaccines against SARS-CoV-2 effectively protect against severe disease, but display incomplete protection against virus transmission. Mucosal vaccines providing immune responses in the upper airways are one strategy to protect against transmission.
We administered Spike HexaPro trimer formulated in a cationic liposomal adjuvant as a parenteral (subcutaneous - s.c.) prime - intranasal boost regimen to elicit airway mucosal immune responses and evaluated this in a Syrian hamster model of virus transmission.
Parenteral prime - intranasal boost elicited high-magnitude serum neutralizing antibody responses and IgA responses in the upper respiratory tract. The vaccine strategy protected against virus in the lower airways and lung pathology, but virus could still be detected in the upper airways. Despite this, the parenteral prime - intranasal booster vaccine effectively protected against onward SARS-CoV-2 transmission.
This study suggests that parenteral-prime mucosal boost is an effective strategy for protecting against SARS-CoV-2 infection and highlights that protection against virus transmission may be obtained despite incomplete clearance of virus from the upper respiratory tract. It should be noted that protection against onward transmission was not compared to standard parenteral prime-boost, which should be a focus for future studies.
This work was primarily supported by the European Union Horizon 2020 research and innovation program under grant agreement no. 101003653.
已获许可的针对 SARS-CoV-2 的疫苗可有效预防重症疾病,但对病毒传播的预防效果不完全。在上呼吸道提供免疫应答的黏膜疫苗是预防传播的一种策略。
我们将六聚体 Spike 与阳离子脂质体佐剂配制在一起,作为一种经皮(皮下-s.c.)初级-鼻内加强方案进行给药,以引发气道黏膜免疫应答,并在病毒传播的叙利亚仓鼠模型中评估该方案。
经皮初级-鼻内加强方案引发了高滴度的血清中和抗体应答和上呼吸道中的 IgA 应答。疫苗策略可预防下呼吸道和肺部病理学中的病毒,但仍可在上呼吸道中检测到病毒。尽管如此,经皮初级-鼻内加强疫苗仍能有效预防 SARS-CoV-2 的传播。
本研究表明,经皮初级-黏膜加强是预防 SARS-CoV-2 感染的有效策略,并强调尽管不能从上呼吸道清除病毒,但仍可获得预防病毒传播的保护。需要注意的是,尚未将针对传播的保护与标准经皮初级-加强方案进行比较,这应是未来研究的重点。
这项工作主要由欧盟地平线 2020 研究和创新计划资助,协议号为 101003653。