Intranasal pediatric parainfluenza virus-vectored SARS-CoV-2 vaccine is protective in monkeys.
Intranasal pediatric parainfluenza virus-vectored SARS-CoV-2 vaccine is protective in monkeys.
复制标题
DOI：
10.1016/j.cell.2022.11.006
复制
发表时间：
2022-12-08
期刊：
影响因子：
64.5
通讯作者：
Buchholz, Ursula J.
中科院分区：
文献类型：
--
作者：
Le Nouen, Cyril;Nelson, Christine E.;Liu, Xueqiao;Park, Hong-Su;Matsuoka, Yumiko;Luongo, Cindy;Santos, Celia;Yang, Lijuan;Herbert, Richard;Castens, Ashley;Moore, Ian N.;Wilder-Kofie, Temeri;Moore, Rashida;Walker, April;Zhang, Peng;Lusso, Paolo;Johnson, Reed F.;Garza, Nicole L.;Via, Laura E.;Munir, Shirin;Barber, Daniel L.;Buchholz, Ursula J.
儿童SARS-CoV-2疫苗需要直接在气道和全身引发免疫。在临床开发的小儿副流感病毒疫苗的基础上，我们产生了表达SARS-CoV-2融合前稳定的刺突（S）蛋白（B/HPIV 3/S-6 P）的减毒活副流感病毒载体疫苗候选物，并在恒河猴中评价了其免疫原性和保护效力。B/HPIV 3/S-6 P单次鼻内/鼻内给药可诱导强烈的S特异性气道粘膜免疫球蛋白A（伊加）和IgG应答。在血清中也诱导了高水平的S特异性抗体，其有效地中和了α、β和δ谱系的SARS-CoV-2变体，而它们中和Omicron亚谱系的能力较低。此外，B/HPIV 3/S-6 P诱导了强烈的全身和肺S特异性CD 4+和CD 8 + T细胞应答，包括肺中的组织驻留记忆细胞。攻击后，SARS-CoV-2复制在免疫猕猴的气道和肺组织中检测不到。B/HPIV 3/S-6 P将作为儿童鼻内SARS-CoV-2/副流感病毒3型疫苗进行临床评价。使用减毒副流感病毒载体可以通过呼吸道在年轻猕猴中有效接种SARS-CoV-2疫苗，这表明人类无针儿科疫苗接种COVID-19是一种有前途的方法。
Pediatric SARS-CoV-2 vaccines are needed that elicit immunity directly in the airways as well as systemically. Building on pediatric parainfluenza virus vaccines in clinical development, we generated a live-attenuated parainfluenza-virus-vectored vaccine candidate expressing SARS-CoV-2 prefusion-stabilized spike (S) protein (B/HPIV3/S-6P) and evaluated its immunogenicity and protective efficacy in rhesus macaques. A single intranasal/intratracheal dose of B/HPIV3/S-6P induced strong S-specific airway mucosal immunoglobulin A (IgA) and IgG responses. High levels of S-specific antibodies were also induced in serum, which efficiently neutralized SARS-CoV-2 variants of concern of alpha, beta, and delta lineages, while their ability to neutralize Omicron sub-lineages was lower. Furthermore, B/HPIV3/S-6P induced robust systemic and pulmonary S-specific CD4+ and CD8+ T cell responses, including tissue-resident memory cells in the lungs. Following challenge, SARS-CoV-2 replication was undetectable in airways and lung tissues of immunized macaques. B/HPIV3/S-6P will be evaluated clinically as pediatric intranasal SARS-CoV-2/parainfluenza virus type 3 vaccine. Use of an attenuated parainfluenza virus vector allows for effective vaccination against SARS-CoV-2 via the airways in young macaques, suggesting a promising approach for needle-free pediatric vaccination of humans against COVID-19.
登录
查看更多内容
DOI：
10.1016/j.xcrm.2021.100230
发表时间：
2021-04-20
期刊：
Cell reports. Medicine
影响因子：
--
作者：
Hassan AO;Feldmann F;Zhao H;Curiel DT;Okumura A;Tang-Huau TL;Case JB;Meade-White K;Callison J;Chen RE;Lovaglio J;Hanley PW;Scott DP;Fremont DH;Feldmann H;Diamond MS
通讯作者：
Diamond MS
影响因子：
56.9
作者：
Hsieh, Ching-Lin;Goldsmith, Jory A.;McLellan, Jason S.
通讯作者：
McLellan, Jason S.
影响因子：
32.4
作者：
Jarjour NN;Masopust D;Jameson SC
通讯作者：
Jameson SC
DOI：
10.1073/pnas.2109744118
发表时间：
2021-12-14
影响因子：
11.1
作者：
Liu X;Luongo C;Matsuoka Y;Park HS;Santos C;Yang L;Moore IN;Afroz S;Johnson RF;Lafont BAP;Martens C;Best SM;Munster VJ;Hollý J;Yewdell JW;Le Nouën C;Munir S;Buchholz UJ
通讯作者：
Buchholz UJ
影响因子：
30.5
作者：
Corbett KS;Werner AP;Connell SO;Gagne M;Lai L;Moliva JI;Flynn B;Choi A;Koch M;Foulds KE;Andrew SF;Flebbe DR;Lamb E;Nurmukhambetova ST;Provost SJ;Bock KW;Minai M;Nagata BM;Ry AV;Flinchbaugh Z;Johnston TS;Mokhtari EB;Mudvari P;Henry AR;Laboune F;Chang B;Porto M;Wear J;Alvarado GS;Boyoglu-Barnum S;Todd JM;Bart B;Cook A;Dodson A;Pessaint L;Steingrebe K;Elbashir S;Sriparna M;Pekosz A;Andersen H;Wu K;Edwards DK;Kar S;Lewis MG;Boritz E;Moore IN;Carfi A;Suthar MS;McDermott A;Roederer M;Nason MC;Sullivan NJ;Douek DC;Graham BS;Seder RA
通讯作者：
Seder RA