An intranasally administered adenovirus-vectored SARS-CoV-2 vaccine induces robust mucosal secretory IgA

作者：Baoqing Sun, Qian Wang, Peiyan Zheng, Xuefeng Niu, Ying Feng, Wei‐jie Guan, Si Chen, Jin Li, Tingting Cui, Yijun Deng, Zhangkai J. Cheng, Yongmei Li, Xinke Zhou, Yi Fang, Wei Wang, Zhongfang Wang, Ling Chen, Nanshan Zhong · 发表于：JCI Insight · 年份：2024 · DOI：10.1172/jci.insight.180784 · 被引用次数：28 · 研究领域：SARS-CoV-2 and COVID-19 Research、Respiratory viral infections research、Immunotherapy and Immune Responses

BACKGROUNDThe level of nasal spike-specific secretory IgA (sIgA) is inversely correlated with the risk of SARS-CoV-2 Omicron infection. This study aimed to evaluate the safety and immunogenicity of intranasal vaccination using Ad5-S-Omicron (NB2155), a replication-incompetent human type 5 adenovirus carrying Omicron BA.1 spike.METHODSAn open-label, single-center, investigator-initiated trial was carried out on 128 health care workers who had never been infected with SARS-CoV-2 and had previously received 2 or 3 injections of inactivated whole-virus vaccines, with the last dose given 3-19 months previously (median 387 days, IQR 333-404 days). Participants received 2 intranasal sprays of NB2155 at 28-day intervals between November 30 and December 30, 2022. Safety was evaluated by solicited adverse events and laboratory tests. The elevation of nasal mucosal spike-specific sIgA and serum neutralizing activities were assessed. All participants were monitored for infection by antigen tests, disease symptoms, and the elevation of nucleocapsid-specific sIgA in the nasal passage.RESULTSThe vaccine-related solicited adverse events were mild. Nasal spike-specific sIgA against 10 strains had a mean geometric mean fold increase of 4.5 after the first dose, but it increased much higher to 51.5 after the second dose. Serum neutralizing titers also increased modestly to 128.1 (95% CI 74.4-220.4) against authentic BA.1 and 76.9 (95% CI 45.4-130.2) against BA.5 at 14 days after the second dose...