Safety and immunogenicity of a live-attenuated influenza virus vector-based intranasal SARS-CoV-2 vaccine in adults: randomised, double-blind, placebo-controlled, phase 1 and 2 trials.
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SUBMITTER: Zhu F
PROVIDER: S-EPMC9135375 | biostudies-literature | 2022 Aug
REPOSITORIES: biostudies-literature
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Safety and immunogenicity of a live-attenuated influenza virus vector-based intranasal SARS-CoV-2 vaccine in adults: randomised, double-blind, placebo-controlled, phase 1 and 2 trials.
Zhu Fengcai F Zhuang Chunlan C Chu Kai K Zhang Liang L Zhao Hui H Huang Shoujie S Su Yingying Y Lin Hongyan H Yang Changlin C Jiang Hanmin H Zang Xia X Liu Donglin D Pan Hongxing H Hu Yuemei Y Liu Xiaohui X Chen Qi Q Song Qiaoqiao Q Quan Jiali J Huang Zehong Z Zhong Guohua G Chen Junyu J Han Jinle J Sun Hong H Cui Lunbiao L Li Jingxin J Chen Yixin Y Zhang Tianying T Ye Xiangzhong X Li Changgui C Wu Ting T Zhang Jun J Xia Ning-Shao NS
The Lancet. Respiratory medicine 20220526 8
<h4>Background</h4>All currently available SARS-CoV-2 vaccines are administered by intramuscular injection. We aimed to evaluate the safety and immunogenicity of a live-attenuated influenza virus vector-based SARS-CoV-2 vaccine (dNS1-RBD) administered by intranasal spray in healthy adults.<h4>Methods</h4>We did double-blind, randomised, placebo-controlled phase 1 and 2 trials, followed by a phase 2 extension trial, at a single centre in Jiangsu, China. Healthy adults (≥18 years) who had negative ...[more]
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Project description:BackgroundInfluenza virus infection is a major public health burden worldwide. Available vaccines include the inactivated intramuscular trivalent vaccine and, more recently, an intranasal live attenuated influenza vaccine (LAIV). The measure of successful vaccination with the inactivated vaccine is a systemic rise in immunoglobulin G (IgG) level, but for the LAIV no such correlate has been established.MethodsSeventy-nine subjects were given the LAIV FluMist. Blood was collected prior to vaccination and 3 days and 30 days after vaccination. Nasal wash was collected 3 days and 30 days after vaccination. Responses were measured systemically and in mucosal secretions for cytokines, cell activation profiles, and antibody responses.ResultsOnly 9% of subjects who received LAIV seroconverted, while 33% of patients developed at least a 2-fold increase in influenza virus-specific immunoglobulin A (IgA) antibodies in nasal wash. LAIV induced a localized inflammation, as suggested by increased expression of interferon-response genes in mucosal RNA and increased granulocyte colony-stimulating factor (G-CSF) and IP-10 in nasal wash. Interestingly, patients who seroconverted had significantly lower serum levels of G-CSF before vaccination.ConclusionsProtection by LAIV is likely provided through mucosal IgA and not by increases in systemic IgG. LAIV induces local inflammation. Seroconversion is achieved in a small fraction of subjects with a lower serum G-CSF level.
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