Safety and tolerability of conserved region vaccines vectored by plasmid DNA, simian adenovirus and modified vaccinia virus ankara administered to human immunodeficiency virus type 1-uninfected adults in a randomized, single-blind phase I trial.
Safety and tolerability of conserved region vaccines vectored by plasmid DNA, simian adenovirus and modified vaccinia virus ankara administered to human immunodeficiency virus type 1-uninfected adults in a randomized, single-blind phase I trial.
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DOI：
10.1371/journal.pone.0101591
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Hanke T
中科院分区：
文献类型：
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作者：
Hayton EJ;Rose A;Ibrahimsa U;Del Sorbo M;Capone S;Crook A;Black AP;Dorrell L;Hanke T
由于病毒抗原多样性、免疫原性差以及最近与人腺病毒5型载体相关的安全性问题，HIV-1疫苗的开发进展缓慢。为了应对HIV-1的变异，我们从HIV-1蛋白质组的功能保守区设计了一种独特的T细胞免疫原HIVconv，该抗原使用质粒DNA、非复制型猿猴(黑猩猩)腺病毒ChAdV-63和非复制型痘病毒改良的痘苗病毒Ankara的异源Prime-Boost组合呈现给免疫系统。一项分组随机、单盲、安慰剂对照的I阶段试验首次向英国牛津32名健康的未感染HIV-1/2的成年人注射了候选HIV-1疫苗或安慰剂，并诱导了能够在体外抑制HIV-1复制的高频率HIV-1特异性T细胞。在这里，详细报道了这些疫苗的安全性和耐受性。使用结构化访谈和研究专用日记卡片收集局部和系统的反应性数据。所有其他不良事件的数据都是通过开放式问题收集的。免疫前后分别检测血清中和抗体滴度。两名志愿者因疫苗无关的原因退出。在190个人月的随访中，没有发生与疫苗相关的严重不良事件或反应。接种疫苗后的局部和系统事件发生在27/32人中，大多数是轻微的(严重程度为1级)，主要是短暂的(48小时)。肌痛和流感样症状与MVA的相关性比ChAdV63或DNA载体更强，在疫苗接受者中比安慰剂更常见。在随访期间没有并发HIV-1感染。2/24名志愿者的ChAdV-63中和滴度在基线水平较低，7名志愿者在接种后将其滴度提高到200以上，中位数(范围)为633(231-1533)，这不是安全问题。这些数据表明pSG2.HIVconv DNA、ChAdV63.HIVconv和MVA.HIVconv疫苗的安全性和良好的耐受性，以及它们的高免疫原性支持它们进一步向疗效研究发展。临床试验.gov NCT01151319
HIV-1 vaccine development has advanced slowly due to viral antigenic diversity, poor immunogenicity and recently, safety concerns associated with human adenovirus serotype-5 vectors. To tackle HIV-1 variation, we designed a unique T-cell immunogen HIVconsv from functionally conserved regions of the HIV-1 proteome, which were presented to the immune system using a heterologous prime-boost combination of plasmid DNA, a non-replicating simian (chimpanzee) adenovirus ChAdV-63 and a non-replicating poxvirus, modified vaccinia virus Ankara. A block-randomized, single-blind, placebo-controlled phase I trial HIV-CORE 002 administered for the first time candidate HIV-1- vaccines or placebo to 32 healthy HIV-1/2-uninfected adults in Oxford, UK and elicited high frequencies of HIV-1-specific T cells capable of inhibiting HIV-1 replication in vitro. Here, detail safety and tolerability of these vaccines are reported. Local and systemic reactogenicity data were collected using structured interviews and study-specific diary cards. Data on all other adverse events were collected using open questions. Serum neutralizing antibody titres to ChAdV-63 were determined before and after vaccination. Two volunteers withdrew for vaccine-unrelated reasons. No vaccine-related serious adverse events or reactions occurred during 190 person-months of follow-up. Local and systemic events after vaccination occurred in 27/32 individuals and most were mild (severity grade 1) and predominantly transient (<48 hours). Myalgia and flu-like symptoms were more strongly associated with MVA than ChAdV63 or DNA vectors and more common in vaccine recipients than in placebo. There were no intercurrent HIV-1 infections during follow-up. 2/24 volunteers had low ChAdV-63-neutralizing titres at baseline and 7 increased their titres to over 200 with a median (range) of 633 (231-1533) post-vaccination, which is of no safety concern. These data demonstrate safety and good tolerability of the pSG2.HIVconsv DNA, ChAdV63.HIVconsv and MVA.HIVconsv vaccines and together with their high immunogenicity support their further development towards efficacy studies. ClinicalTrials.gov NCT01151319
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HIV-1 GAG中的簇突变是逃避HLA-B27限制的细胞毒性T淋巴细胞反应所必需的。
影响因子：
15.3
作者：
Kelleher, A D;Long, C;Holmes, E C;Allen, R L;Wilson, J;Conlon, C;Workman, C;Shaunak, S;Olson, K;Goulder, P;Brander, C;Ogg, G;Sullivan, J S;Dyer, W;Jones, I;McMichael, A J;Rowland-Jones, S;Phillips, R E
通讯作者：
Phillips, R E
影响因子：
32.4
作者：
Ferguson AL;Mann JK;Omarjee S;Ndung'u T;Walker BD;Chakraborty AK
通讯作者：
Chakraborty AK
影响因子：
11.8
作者：
Bejon, P;Peshu, N;Marsh, K
通讯作者：
Marsh, K
影响因子：
168.9
作者：
Buchbinder, Susan P.;Mehrotra, Devon V.;Duerr, Ann;Fitzgerald, Daniel W.;Mogg, Robin;Li, David;Gilbert, Peter B.;Lama, Javier R.;Marmor, Michael;del Rio, Carlos;McElrath, M. Juliana;Casimiro, Danilo R.;Gottesdiener, Keith M.;Chodakewitz, Jeffrey A.;Corey, Lawrence;Robertson, Michael N.
通讯作者：
Robertson, Michael N.
疫苗吸引的人T细胞识别保守的蛋白质区域抑制HIV-1。
DOI：
10.1038/mt.2013.248
发表时间：
2014-02
期刊：
Molecular therapy : the journal of the American Society of Gene Therapy
影响因子：
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作者：
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