Tolerability and immunogenicity of an intranasally-administered adenovirus-vectored COVID-19 vaccine: An open-label partially-randomised ascending dose phase I trial.
Tolerability and immunogenicity of an intranasally-administered adenovirus-vectored COVID-19 vaccine: An open-label partially-randomised ascending dose phase I trial.
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DOI：
10.1016/j.ebiom.2022.104298
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发表时间：
2022-11
期刊：
影响因子：
11.1
通讯作者：
Douglas, Alexander D.
中科院分区：
文献类型：
--
作者：
Madhavan, Meera;Ritchie, Adam J.;Aboagye, Jeremy;Jenkin, Daniel;Provstgaad-Morys, Samuel;Tarbet, Iona;Woods, Danielle;Davies, Sophie;Baker, Megan;Platt, Abigail;Flaxman, Amy;Smith, Holly;Belij-Rammerstorfer, Sandra;Wilkins, Deidre;Kelly, Elizabeth J.;Villafana, Tonya;Green, Justin A.;Poulton, Ian;Lambe, Teresa;Hill, Adrian V. S.;Ewer, Katie J.;Douglas, Alexander D.
鼻腔接种可诱导对呼吸道病原体的保护性局部和系统免疫反应。一些SARS-CoV-2鼻内候选疫苗已在临床前挑战模型中获得保护，包括ChAdOx1 nCoV-19(AZD1222，牛津大学/阿斯利康)。我们在健康成年人中进行了单中心开放式标签第一阶段鼻腔接种ChAdOx1 nCoV-19的临床试验，使用的是为肌肉注射生产的现有配方。30名SARS-CoV-2疫苗幼稚参与者被分配为接种5×109病毒颗粒(VP，n=6)、2×1010 VP(n=12)或5×1010 VP(n=12)。28天后，14人接受了第二次鼻腔注射。另有12人在研究第22至46天期间接受了非研究肌肉内注射SARS-CoV-2疫苗。为了研究鼻内注射ChAdOx1 nCoV-19的作用，6名之前接受过两次肌肉注射ChAdOx1 nCoV-19的参与者和6名接受过两次肌肉注射BNT162b2(辉瑞/BioNTech)的参与者被给予单次鼻腔注射5×1010VP的ChAdOx1 nCoV-19。目的是评估安全性(一级)和粘膜抗体反应(二级)。反应性为轻度或中度。在少数参与者中可以检测到对鼻腔接种疫苗的抗原特异性粘膜抗体反应，很少超过SARS-CoV-2感染后的水平。鼻腔接种的全身反应通常弱于肌肉接种ChAdOx1nCoV-19。在鼻腔接种后接受肌肉注射mRNA疫苗的参与者中可以检测到抗原特异性粘膜抗体。7名参与者出现了有症状的SARS-CoV-2感染。这种鼻腔注射ChAdOx1nCoV-19的配方显示出可接受的耐受性，但既没有诱导一致的粘膜抗体反应，也没有诱导强烈的全身反应。阿斯利康。
Intranasal vaccination may induce protective local and systemic immune responses against respiratory pathogens. A number of intranasal SARS-CoV-2 vaccine candidates have achieved protection in pre-clinical challenge models, including ChAdOx1 nCoV-19 (AZD1222, University of Oxford / AstraZeneca). We performed a single-centre open-label Phase I clinical trial of intranasal vaccination with ChAdOx1 nCoV-19 in healthy adults, using the existing formulation produced for intramuscular administration. Thirty SARS-CoV-2 vaccine-naïve participants were allocated to receive 5 × 109 viral particles (VP, n=6), 2 × 1010 VP (n=12), or 5 × 1010 VP (n=12). Fourteen received second intranasal doses 28 days later. A further 12 received non-study intramuscular mRNA SARS-CoV-2 vaccination between study days 22 and 46. To investigate intranasal ChAdOx1 nCoV-19 as a booster, six participants who had previously received two intramuscular doses of ChAdOx1 nCoV-19 and six who had received two intramuscular doses of BNT162b2 (Pfizer / BioNTech) were given a single intranasal dose of 5 × 1010 VP of ChAdOx1 nCoV-19. Objectives were to assess safety (primary) and mucosal antibody responses (secondary). Reactogenicity was mild or moderate. Antigen-specific mucosal antibody responses to intranasal vaccination were detectable in a minority of participants, rarely exceeding levels seen after SARS-CoV-2 infection. Systemic responses to intranasal vaccination were typically weaker than after intramuscular vaccination with ChAdOx1 nCoV-19. Antigen-specific mucosal antibody was detectable in participants who received an intramuscular mRNA vaccine after intranasal vaccination. Seven participants developed symptomatic SARS-CoV-2 infection. This formulation of intranasal ChAdOx1 nCoV-19 showed an acceptable tolerability profile but induced neither a consistent mucosal antibody response nor a strong systemic response. AstraZeneca.
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影响因子：
6.4
作者：
Bagga, Bindiya;Cehelsky, Jeffrey E.;DeVincenzo, John P.
通讯作者：
DeVincenzo, John P.
对新型冠状病毒（SARS-COV-2）疫苗的粘膜和血清学免疫反应。
影响因子：
7.3
作者：
Chan RWY;Liu S;Cheung JY;Tsun JGS;Chan KC;Chan KYY;Fung GPG;Li AM;Lam HS
通讯作者：
Lam HS
DOI：
10.1056/nejmoa2104840
发表时间：
2021-06-03
期刊：
The New England journal of medicine
影响因子：
--
作者：
Greinacher A;Thiele T;Warkentin TE;Weisser K;Kyrle PA;Eichinger S
通讯作者：
Eichinger S
影响因子：
8.8
作者：
Mulay A;Konda B;Garcia G Jr;Yao C;Beil S;Villalba JM;Koziol C;Sen C;Purkayastha A;Kolls JK;Pociask DA;Pessina P;de Aja JS;Garcia-de-Alba C;Kim CF;Gomperts B;Arumugaswami V;Stripp BR
通讯作者：
Stripp BR
影响因子：
11.1
作者：
Alu A;Chen L;Lei H;Wei Y;Tian X;Wei X
通讯作者：
Wei X