Safety and Immunogenicity of Pfs25-EPA/Alhydrogel®, a Transmission Blocking Vaccine against Plasmodium falciparum: An Open Label Study in Malaria Naïve Adults.
Safety and Immunogenicity of Pfs25-EPA/Alhydrogel®, a Transmission Blocking Vaccine against Plasmodium falciparum: An Open Label Study in Malaria Naïve Adults.
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DOI：
10.1371/journal.pone.0163144
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发表时间：
2016
期刊：
影响因子：
3.7
通讯作者：
Duffy PE
中科院分区：
文献类型：
--
作者：
Talaat KR;Ellis RD;Hurd J;Hentrich A;Gabriel E;Hynes NA;Rausch KM;Zhu D;Muratova O;Herrera R;Anderson C;Jones D;Aebig J;Brockley S;MacDonald NJ;Wang X;Fay MP;Healy SA;Durbin AP;Narum DL;Wu Y;Duffy PE
针对性阶段寄生虫发育的传播阻断疫苗可以成为消除疟疾措施的一个组成部分。Pfs 25是一种领先的TBV候选物，先前在动物中进行的研究表明，与EPA（一种来自铜绿假单胞菌的重组脱毒外蛋白A）缀合后，其功能性免疫原性得到改善。在本报告中，我们描述了一项开放标签、剂量递增的1期试验的结果，该试验旨在评估用Alhydrogel®配制的Pfs 25-EPA缀合物的安全性和免疫原性。30名初治疟疾的健康成人在0、2、4和10个月时接受多达4剂结合疫苗，8、16或47 μg结合Pfs 25质量。接种疫苗一般耐受良好。大多数征集性不良事件的严重程度为轻度，注射部位疼痛是最常见的主诉。贫血是最常见的实验室检查异常，但认为仅在少数病例中可能与研究相关。未发生与疫苗相关的严重不良事件。最高剂量组抗Pfs 25抗体几何均值峰值在第4次接种后2周为88（95% CI 53，147）μg/mL，1年后下降至接近基线水平。抗体亲合力随连续接种而增加。在标准膜饲养试验（SMFA）中证明的传输阻断活性也从第二次给药至第三次给药增加，并与抗体滴度相关，最终给药后与抗体亲合力相关。这些结果支持进一步评估Pfs 25-EPA/Alhydrogel®在疟疾流行人群中的作用。
Transmission-blocking vaccines (TBVs) that target sexual stage parasite development could be an integral part of measures for malaria elimination. Pfs25 is a leading TBV candidate, and previous studies conducted in animals demonstrated an improvement of its functional immunogenicity after conjugation to EPA, a recombinant, detoxified ExoProtein A from Pseudomonas aeruginosa. In this report, we describe results of an open-label, dose-escalating Phase 1 trial to assess the safety and immunogenicity of Pfs25-EPA conjugates formulated with Alhydrogel®. Thirty malaria-naïve healthy adults received up to four doses of the conjugate vaccine, with 8, 16, or 47 μg of conjugated Pfs25 mass, at 0, 2, 4, and 10 months. Vaccinations were generally well tolerated. The majority of solicited adverse events were mild in severity with pain at the injection site the most common complaint. Anemia was the most common laboratory abnormality, but was considered possibly related to the study in only a minority of cases. No vaccine-related serious adverse events occurred. The peak geometric mean anti-Pfs25 antibody level in the highest dose group was 88 (95% CI 53, 147) μg/mL two weeks after the 4th vaccination, and declined to near baseline one year later. Antibody avidity increased over successive vaccinations. Transmission blocking activity demonstrated in a standard membrane feeding assay (SMFA) also increased from the second to the third dose, and correlated with antibody titer and, after the final dose, with antibody avidity. These results support the further evaluation of Pfs25-EPA/Alhydrogel® in a malaria-endemic population.
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影响因子：
6.4
作者：
Ashkenazi, S;Passwell, JH;Schneerson, R
通讯作者：
Schneerson, R
影响因子：
4
作者：
Churcher, Thomas S.;Blagborough, Andrew M.;Sinden, Robert E.
通讯作者：
Sinden, Robert E.
DOI：
10.4269/ajtmh.1992.47.41
发表时间：
1992-07-01
影响因子：
3.3
作者：
BEIER, JC;COPELAND, RS;VAUGHAN, JA
通讯作者：
VAUGHAN, JA
影响因子：
5.5
作者：
Qian, Feng;Rausch, Kelly M.;Mullen, Gregory E. D.
通讯作者：
Mullen, Gregory E. D.
影响因子：
3.7
作者：
Ellis RD;Wu Y;Martin LB;Shaffer D;Miura K;Aebig J;Orcutt A;Rausch K;Zhu D;Mogensen A;Fay MP;Narum DL;Long C;Miller L;Durbin AP
通讯作者：
Durbin AP