美国国立卫生研究院Robert A. Seder等研究人员合作发现，黏膜腺病毒疫苗加强接种可引发IgA反应并在非人灵长类动物中持久地预防XBB.1.16感染。相关论文于2024年9月3日在线发表在《自然—免疫学》杂志上。

研究人员表示，通过黏膜途径进行疫苗接种可以在感染部位防止严重急性呼吸综合征冠状病毒2（SARS-CoV-2）的复制并限制传播。

研究人员比较了在非人灵长类动物（NHP）中，在肌肉内加强接种编码WA1和BA.5刺突蛋白的双价mRNA疫苗约5个月后，与通过鼻腔或气溶胶设备递送的WA1-BA.5双价黑猩猩腺病毒载体疫苗的黏膜加强接种后，对异源XBB.1.16挑战的保护效果。通过任一黏膜途径加强接种的NHP在鼻腔和肺部的病毒复制均极少。

相比之下，肌肉内mRNA疫苗的保护作用仅限于下呼吸道。黏膜递送的疫苗引发了持久的气道IgG和IgA反应，并且与肌肉内mRNA疫苗不同，在肺部诱导了针对刺突蛋白的B细胞。IgG、IgA和T细胞反应与肺部的保护相关，而黏膜IgA则与上呼吸道的保护相关。该研究突出了黏膜和血清保护作用的不同相关性，并展示了黏膜疫苗如何持久地预防SARS-CoV-2感染。

附：英文原文

Title: Mucosal adenovirus vaccine boosting elicits IgA and durably prevents XBB.1.16 infection in nonhuman primates

Author: Gagne, Matthew, Flynn, Barbara J., Andrew, Shayne F., Marquez, Josue, Flebbe, Dillon R., Mychalowych, Anna, Lamb, Evan, Davis-Gardner, Meredith E., Burnett, Matthew R., Serebryannyy, Leonid A., Lin, Bob C., Ziff, Zohar E., Maule, Erin, Carroll, Robin, Naisan, Mursal, Jethmalani, Yogita, Pessaint, Laurent, Todd, John-Paul M., Doria-Rose, Nicole A., Case, James Brett, Dmitriev, Igor P., Kashentseva, Elena A., Ying, Baoling, Dodson, Alan, Kouneski, Katelyn, ODell, Sijy, Wali, Bushra, Ellis, Madison, Godbole, Sucheta, Laboune, Farida, Henry, Amy R., Teng, I-Ting, Wang, Danyi, Wang, Lingshu, Zhou, Qiong, Zouantchangadou, Serge, Van Ry, Alex, Lewis, Mark G., Andersen, Hanne, Kwong, Peter D., Curiel, David T., Roederer, Mario, Nason, Martha C., Foulds, Kathryn E., Suthar, Mehul S., Diamond, Michael S., Douek, Daniel C., Seder, Robert A.

Issue&Volume: 2024-09-03

Abstract: A mucosal route of vaccination could prevent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) replication at the site of infection and limit transmission. We compared protection against heterologous XBB.1.16 challenge in nonhuman primates (NHPs) ~5 months following intramuscular boosting with bivalent mRNA encoding WA1 and BA.5 spike proteins or mucosal boosting with a WA1–BA.5 bivalent chimpanzee adenoviral-vectored vaccine delivered by intranasal or aerosol device. NHPs boosted by either mucosal route had minimal virus replication in the nose and lungs, respectively. By contrast, protection by intramuscular mRNA was limited to the lower airways. The mucosally delivered vaccine elicited durable airway IgG and IgA responses and, unlike the intramuscular mRNA vaccine, induced spike-specific B cells in the lungs. IgG, IgA and T cell responses correlated with protection in the lungs, whereas mucosal IgA alone correlated with upper airway protection. This study highlights differential mucosal and serum correlates of protection and how mucosal vaccines can durably prevent infection against SARS-CoV-2. Seder and colleagues show that mucosal adenoviral-vectored vaccine boosting durably prevents infection in nonhuman primates of the highly transmissible, heterologous XBB.1.16 strain of SARS-CoV-2.

DOI: 10.1038/s41590-024-01951-5

Source: https://www.nature.com/articles/s41590-024-01951-5