A vaccine remains a priority in the global fight against malaria. Here, we report on a single-center, randomized, double-blind, placebo and adjuvant-controlled, dose escalation phase 1a safety and immunogenicity clinical trial of full-length Plasmodium falciparum merozoite surface protein 1 (MSP1) in combination with GLA-SE adjuvant. Thirty-two healthy volunteers were vaccinated at least three times with MSP1 plus adjuvant, adjuvant alone, or placebo (24:4:4) to evaluate the safety and immunogenicity. MSP1 was safe, well tolerated and immunogenic, with all vaccinees sero-converting independent of the dose. The MSP1-specific IgG and IgM titers persisted above levels found in malaria semi-immune humans for at least 6 months after the last immunization. The antibodies were variant- and strain-transcending and stimulated respiratory activity in granulocytes. Furthermore, full-length MSP1 induced memory T-cells. Our findings encourage challenge studies as the next step to evaluate the efficacy of full-length MSP1 as a vaccine candidate against falciparum malaria (EudraCT 2016-002463-33).

译文

:在全球抗击疟疾的斗争中,疫苗仍然是优先事项。在这里,我们报告了全长恶性疟原虫裂殖子表面蛋白1(MSP1)与GLA-SE结合使用的单中心,随机,双盲,安慰剂和佐剂控制的剂量递增阶段1a安全性和免疫原性临床试验佐剂。对32名健康志愿者进行了至少3次MSP1加佐剂,单独佐剂或安慰剂的疫苗接种(24:4:4),以评估其安全性和免疫原性。 MSP1是安全的,耐受性良好且具有免疫原性,所有疫苗的血清转化都与剂量无关。上次免疫后至少六个月,MSP1特异性IgG和IgM滴度持续高于疟疾半免疫人群中发现的水平。该抗体具有超越变体和应变的特性,并能刺激粒细胞的呼吸活性。此外,全长MSP1诱导了记忆T细胞。我们的发现鼓励进行挑战性研究,作为评估全长MSP1作为抗恶性疟疾疫苗候选者的功效的下一步(EudraCT 2016-002463-33)。

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