Sirima Sodiomon B, Nébié Issa, Ouédraogo Alphonse, Tiono Alfred B, Konaté Amadou T, Gansané Adama, Dermé Assetou I, Diarra Amidou, Ouédraogo Amidou, Soulama Issiaka, Cuzzin-Ouattara Nadine, Cousens Simon, Leroy Odile
Centre National de Recherche et de Formation sur le Paludisme (CNRFP), 01 BP 2208 Ouagadougou 01, Burkina Faso.
Vaccine. 2007 Mar 30;25(14):2723-32. doi: 10.1016/j.vaccine.2006.05.090. Epub 2006 Jun 16.
The merozoite surface protein-3 long synthetic peptide (MSP3-LSP) comprises the amino acid sequence 186-276 of the Plasmodium falciparum protein MSP3. It is currently in development as an erythrocytic stage (blood stage) malaria vaccine candidate. We report here the first data on the safety, reactogenicity and immunogenicity of three doses of MSP3-LSP, adjuvanted with aluminium hydroxide, in healthy male adults living in a malaria endemic area.
A phase 1b single-blind controlled trial was performed in the village of Balonghin in Burkina Faso. Thirty male volunteers aged 18-40 years were randomised to receive either three doses of 30 microg MSP3-LSP or 0.5 ml of tetanus toxoid vaccine. The second and third vaccine doses were given 28 and 112 days after the first dose. We followed participants for 1 year.
There were no serious adverse events in either vaccine group. In both groups participants reported local reactions at the site of injection when compared to an earlier trial in European volunteers. Only one systemic adverse event (tachycardia) was identified which occurred immediately after the first vaccination in one individual receiving MSP3-LSP. No clinically significant biological abnormalities following vaccination were observed. Humoral immune responses (IgG, IgG subclasses, IgM) to MSP3-LSP peptide were similar in the two groups following vaccination. Some cell-mediated immune responses appeared to differ between the two vaccine groups. After the second dose of MSP3-LSP, there appeared to be a marked increase in the lymphocyte proliferation index and IFN-gamma in response to stimulation with MSP3-LSP.
These data suggest that three doses of 30 microg MSP3-LSP when administered subcutaneously on days 0, 28 and 112 are well-tolerated by adult males previously exposed to natural P. falciparum infection. They also suggest that MSP3-LSP is able to stimulate an enhanced cell-mediated immune response in individuals with some degree of preexisting immunity.
裂殖子表面蛋白-3长合成肽（MSP3-LSP）包含恶性疟原虫蛋白MSP3的氨基酸序列186 - 276。它目前正作为红细胞期（血液期）疟疾疫苗候选物进行研发。我们在此报告在疟疾流行地区生活的健康成年男性中，三剂用氢氧化铝佐剂的MSP3-LSP的安全性、反应原性和免疫原性的首批数据。
在布基纳法索的巴隆欣村进行了一项1b期单盲对照试验。30名年龄在18 - 40岁的男性志愿者被随机分配接受三剂30微克的MSP3-LSP或0.5毫升破伤风类毒素疫苗。第二剂和第三剂疫苗分别在第一剂后的28天和112天接种。我们对参与者进行了1年的随访。
两个疫苗组均未出现严重不良事件。与早期在欧洲志愿者中进行的试验相比，两组参与者均报告了注射部位的局部反应。仅发现一例全身不良事件（心动过速），发生在一名接受MSP3-LSP的个体首次接种疫苗后立即出现。接种疫苗后未观察到临床上有显著意义的生物学异常。接种疫苗后，两组对MSP3-LSP肽的体液免疫反应（IgG、IgG亚类、IgM）相似。两个疫苗组之间的一些细胞介导免疫反应似乎有所不同。在第二剂MSP3-LSP后，对MSP3-LSP刺激的淋巴细胞增殖指数和干扰素-γ似乎有明显增加。
这些数据表明，在第0、28和112天皮下注射三剂30微克的MSP3-LSP，先前暴露于自然恶性疟原虫感染的成年男性耐受性良好。它们还表明，MSP3-LSP能够在具有一定程度预先存在免疫力的个体中刺激增强的细胞介导免疫反应。
