{"id":21946,"date":"2022-07-28T04:49:00","date_gmt":"2022-07-27T20:49:00","guid":{"rendered":"http:\/\/csccm.org.cn\/?p=21946"},"modified":"2022-07-28T05:24:59","modified_gmt":"2022-07-27T21:24:59","slug":"lancet-respir-med%e5%8f%91%e8%a1%a8%e8%ae%ba%e6%96%87%ef%bc%9a%e5%9f%ba%e4%ba%8e%e5%87%8f%e6%af%92%e6%b5%81%e6%84%9f%e7%97%85%e6%af%92%e8%bd%bd%e4%bd%93%e7%9a%84%e9%bc%bb%e5%96%b7%e6%96%b0%e5%86%a0","status":"publish","type":"post","link":"https:\/\/csccm.org.cn\/?p=21946","title":{"rendered":"[Lancet Respir Med\u53d1\u8868\u8bba\u6587]\uff1a\u57fa\u4e8e\u51cf\u6bd2\u6d41\u611f\u75c5\u6bd2\u8f7d\u4f53\u7684\u9f3b\u55b7\u65b0\u51a0\u75c5\u6bd2\u75ab\u82d7\u5bf9\u6210\u4eba\u7684\u5b89\u5168\u6027\u53ca\u514d\u75ab\u539f\u6027"},"content":{"rendered":"\n

ARTICLES|ONLINE FIRST<\/a><\/p>\n\n\n\n

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<\/h1>\n\n\n\n

Fengcai Zhu, Chunlan Zhuang, Kai Chu, et al<\/h3>\n\n\n\n

Lancet Respir Med Published:May 26, 2022<\/h3>\n\n\n\n

DOI:https:\/\/doi.org\/10.1016\/S2213-2600(22)00131-X<\/a><\/h3>\n\n\n\n

Summary<\/h2>\n\n\n\n

Background<\/h3>\n\n\n\n

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.<\/p>\n\n\n\n

Methods<\/h3>\n\n\n\n

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 (\u226518 years) who had negative serum or fingertip blood total antibody tests for SARS-CoV-2 (in phases 1 and 2), with no prevalent SARS-CoV-2 infection or history of infection and no SARS-CoV-2 vaccination history (in all three trials reported here), were enrolled. Participants were randomly allocated (4:1 in phase 1, 2:1 in phase 2, and 1:1 in the extension trial) to receive two intranasal doses of the dNS1-RBD vaccine or placebo on days 0 and 14 or, for half of the participants in phase 2, on days 0 and 21. To avoid cross-contamination during administration, vaccine and placebo recipients were vaccinated in separate rooms in the extension trial. The phase 1 primary outcome was safety (adverse events recorded on days 0\u201344; serious adverse events recorded from day 0 until 12 months after the second dose). In the phase 2 and extension trials, the primary immunogenicity outcomes were SARS-CoV-2-specific T-cell response in peripheral blood (measured by IFN-\u03b3 ELISpot), proportion of participants with positive conversion for SARS-CoV-2 receptor-binding domain (RBD)-specific IgG and secretory IgA (s-IgA) antibodies, and concentration of SARS-CoV-2 RBD IgG in serum and SARS-CoV-2 RBD s-IgA in the nasopharynx (measured by ELISA) at 1 month after the second dose in the per-protocol set for immunogenicity. \u03c72<\/sup> test and Fisher's exact test were used to analyse categorical data, and t<\/em> test and Wilcoxon rank sum test to compare the measurement data between groups. These trials were registered with the Chinese Clinical Trial Registry (ChiCTR2000037782, ChiCTR2000039715, and ChiCTR2100048316).<\/p>\n\n\n\n

Findings<\/h3>\n\n\n\n

Between Sept 1, 2020, and July 4, 2021, 63, 724, and 297 participants without a history of SARS-CoV-2 vaccination were enrolled in the phase 1, phase 2, and extension trials, respectively. At least one adverse reaction after vaccination was reported in 133 (19%) of 684 participants in the vaccine groups. Most adverse reactions were mild. No vaccine-related serious adverse event was noted. Specific T-cell immune responses were observed in 211 (46% [95% CI 42\u201351]) of 455 vaccine recipients in the phase 2 trial, and in 48 (40% [31\u201349]) of 120 vaccine recipients compared with one (1% [0\u20135]) of 111 placebo recipients (p<0\u00b70001) in the extension trial. Seroconversion for RBD-specific IgG was observed in 48 (10% [95% CI 8\u201313]) of 466 vaccine recipients in the phase 2 trial (geometric mean titre [GMT] 3\u00b78 [95% CI 3\u00b74\u20134\u00b73] in responders), and in 31 (22% [15\u201329]) of 143 vaccine recipients (GMT 4\u00b74 [3\u00b73\u20135\u00b78]) and zero (0% [0\u20132]) of 147 placebo recipients (p<0\u00b70001) in the extension trial. 57 (12% [95% CI 9\u201316]) of 466 vaccine recipients had positive conversion for RBD-specific s-IgA (GMT 3\u00b78 [95% CI 3\u00b75\u20134\u00b71] in responders) in the phase 2 trial, as did 18 (13% [8\u201319]) of 143 vaccine recipients (GMT 5\u00b72 [4\u00b70\u20136\u00b78]) and zero (0% [0\u20132]) of 147 placebo recipients (p<0\u00b70001) in the extension trial.<\/p>\n\n\n\n

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Interpretation<\/h3>\n\n\n\n

dNS1-RBD was well tolerated in adults. Weak T-cell immunity in peripheral blood, as well as weak humoral and mucosal immune responses against SARS-CoV-2, were detected in vaccine recipients. Further studies are warranted to verify the safety and efficacy of intranasal vaccines as a potential supplement to current intramuscular SARS-CoV-2 vaccine pools. Steps should be taken in future studies to reduce the potential for cross-contamination caused by the vaccine strain aerosol during administration.<\/p>\n\n\n\n

Funding<\/h3>\n\n\n\n

National Key Research and Development Program of China, National Science, Fujian Provincial Science, CAMS Innovation Fund for Medical Sciences, and Beijing Wantai Biological Pharmacy Enterprise.<\/p>\n","protected":false},"excerpt":{"rendered":"

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