Safety and immunogenicity of a live attenuated RSV vaccine in healthy RSV-seronegative children 5 to 24 months of age.
Safety and immunogenicity of a live attenuated RSV vaccine in healthy RSV-seronegative children 5 to 24 months of age.
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DOI：
10.1371/journal.pone.0077104
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Dubovsky F
中科院分区：
文献类型：
--
作者：
Malkin E;Yogev R;Abughali N;Sliman J;Wang CK;Zuo F;Yang CF;Eickhoff M;Esser MT;Tang RS;Dubovsky F
尽管与呼吸道合胞病毒（RSV）感染相关的发病率很高，但目前还没有获得许可的疫苗。MEDI-559是一种正在开发的鼻内减毒活疫苗候选物，用于预防幼儿RSV引起的下呼吸道疾病。这项随机、安慰剂对照研究评价了MEDI-559在健康、RSV血清阴性儿童中的安全性。MEDI-559或安慰剂给药3次，间隔2个月。主要安全性基于每次给药后28天收集的征集性症状（SS）和不良事件（AE）。每次给药后（第7-10、12-18、28-34天）和患病访视时采集3次鼻洗液样本。在首次接种前和末次接种后28天采集血清，用于测量对RSV的抗体免疫应答。从首次给药起监测365天的长期安全性。SS为轻度和频繁（MEDI-559 84%;安慰剂91%）;最常见的SS为流鼻涕/鼻塞、咳嗽和易怒/烦躁。67%的MEDI-559和57%的安慰剂接受者发生AE：最常见的AE是上呼吸道感染（MEDI-559 35%;安慰剂23%）。与安慰剂组相比，MEDI-559组在给药后28天内接受医疗护理的下呼吸道疾病的发生率更高（与疫苗病毒脱落无关）。没有证据表明RSV疾病增强。仅在MEDI-559接种者中检测到疫苗病毒; 56%的受试者发生脱落，主要发生在第1次接种后。通过RSV微量中和试验，分别在59%和9%的MEDI-559和安慰剂接受者中观察到功能性免疫应答。在95%的MEDI-559受试者中观察到疫苗接种，通过脱落疫苗型病毒或对RSV有血清应答的比例进行评估。因此，MEDI-559在该血清阴性儿科人群中具有生物活性和免疫原性。尽管SS和AE的频率被认为不具有临床意义，但疫苗组中接受医学治疗的下呼吸道疾病的增加值得扩大安全性研究。ClinicalTrials.gov NCT00767416
Despite substantial morbidity associated with respiratory syncytial virus (RSV) infection, there is no licensed vaccine. MEDI-559 is a live attenuated intranasal vaccine candidate being developed for prevention of lower respiratory illness due to RSV in young children. This randomized, placebo-controlled study evaluated safety of MEDI-559 in healthy, RSV-seronegative children. MEDI-559 or placebo was administered on 3 occasions, 2 months apart. Primary safety was based on solicited symptoms (SSs) and adverse events (AEs) collected for 28 days after each dose. Nasal wash samples were collected 3 times after each dose (days 7-10, 12-18, 28-34) and at sick visits. Serum was collected for measuring antibody immune responses to RSV prior to first vaccination and 28 days post final dose. Long-term safety was monitored for 365 days from first dose. SSs were mild and frequent (MEDI-559 84%; placebo 91%); most common SSs were runny/stuffy nose, cough, and irritability/fussiness. AEs occurred in 67% MEDI-559 and 57% placebo recipients: most common AE was upper respiratory tract infection (MEDI-559 35%; placebo 23%). Higher incidence of medically attended lower respiratory illness within 28 days after dosing occurred in the MEDI-559 arm compared to placebo (none associated with vaccine virus shedding). There was no evidence of enhanced RSV disease. Vaccine virus was detected only in MEDI-559 recipients; shedding occurred in 56%subjects, primarily post dose 1. A functional immune response was observed in 59% and 9% MEDI-559 and placebo recipients, respectively, by an RSV microneutralization assay. Vaccine take, assessed by proportion that shed vaccine-type virus or had a seroresponse against RSV, was seen in 95% MEDI-559 subjects. MEDI-559 is therefore biologically active and immunogenic in this seronegative pediatric population. Although the frequency of SSs and AEs was not considered clinically significant, the increase in medically attended lower respiratory illnesses in the vaccine group warrants expanded safety studies. ClinicalTrials.gov NCT00767416
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DOI：
10.1056/nejmoa0804877
发表时间：
2009-02-05
期刊：
The New England journal of medicine
影响因子：
--
作者：
Hall CB;Weinberg GA;Iwane MK;Blumkin AK;Edwards KM;Staat MA;Auinger P;Griffin MR;Poehling KA;Erdman D;Grijalva CG;Zhu Y;Szilagyi P
通讯作者：
Szilagyi P
影响因子：
3.6
作者：
Stockman, Lauren J.;Curns, Aaron T.;Fischer-Langley, Gayle
通讯作者：
Fischer-Langley, Gayle
影响因子：
168.9
作者：
Nair, Harish;Nokes, D. James;Gessner, Bradford D.;Dherani, Mukesh;Madhi, Shabir A.;Singleton, Rosalyn J.;O'Brien, Katherine L.;Roca, Anna;Wright, Peter F.;Bruce, Nigel;Chandran, Aruna;Theodoratou, Evropi;Sutanto, Agustinus;Sedyaningsih, Endang R.;Ngama, Mwanajuma;Munywoki, Patrick K.;Kartasasmita, Cissy;Simoes, Eric A. F.;Rudan, Igor;Weber, Martin W.;Campbell, Harry
通讯作者：
Campbell, Harry
影响因子：
158.5
作者：
Belshe, Robert B.;Edwards, Kathryn M.;Connor, Edward M.
通讯作者：
Connor, Edward M.
影响因子：
3.6
作者：
Bernstein, David I.;Malkin, Elissa;Dubovsky, Filip
通讯作者：
Dubovsky, Filip