疟疾预防用单克隆抗体。
A Monoclonal Antibody for Malaria Prevention.
机构信息
From the Vaccine Research Center (M.R.G., N.M.B., A.H.I., E.E.C., L.A.H., F.M., I.J.G., S.H.P., O.T., S.O., M.B., N.D., S.R.N., C.R.B., A.T.W., R.H., S.F.A., R.L.W., S.H., D.W., J.A.S., K.C., J.G.G., S.V., B.F., G.L.C., J.R.F., B.J.F., N.K.K., A.M., J.R.M., J.E.L., R.A.S.) and the Biostatistics Research Branch, Division of Clinical Research (Z.H.), National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, the U.S. Public Health Service Commissioned Corps, Rockville (M.R.G.), the Entomology Branch, Walter Reed Army Institute of Research, Silver Spring (A.C.C., B.P.E.), and the Vaccine Clinical Materials Program, Leidos Biomedical Research, Frederick National Laboratory for Cancer Research, Frederick (C.C.) - all in Maryland; and the School of Medicine and Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, San Diego (E.V.C.).
出版信息
N Engl J Med. 2021 Aug 26;385(9):803-814. doi: 10.1056/NEJMoa2034031. Epub 2021 Aug 11.
BACKGROUND
Additional interventions are needed to reduce the morbidity and mortality caused by malaria.
METHODS
We conducted a two-part, phase 1 clinical trial to assess the safety and pharmacokinetics of CIS43LS, an antimalarial monoclonal antibody with an extended half-life, and its efficacy against infection with . Part A of the trial assessed the safety, initial side-effect profile, and pharmacokinetics of CIS43LS in healthy adults who had never had malaria. Participants received CIS43LS subcutaneously or intravenously at one of three escalating dose levels. A subgroup of participants from Part A continued to Part B, and some received a second CIS43LS infusion. Additional participants were enrolled in Part B and received CIS43LS intravenously. To assess the protective efficacy of CIS43LS, some participants underwent controlled human malaria infection in which they were exposed to mosquitoes carrying sporozoites 4 to 36 weeks after administration of CIS43LS.
RESULTS
A total of 25 participants received CIS43LS at a dose of 5 mg per kilogram of body weight, 20 mg per kilogram, or 40 mg per kilogram, and 4 of the 25 participants received a second dose (20 mg per kilogram regardless of initial dose). No safety concerns were identified. We observed dose-dependent increases in CIS43LS serum concentrations, with a half-life of 56 days. None of the 9 participants who received CIS43LS, as compared with 5 of 6 control participants who did not receive CIS43LS, had parasitemia according to polymerase-chain-reaction testing through 21 days after controlled human malaria infection. Two participants who received 40 mg per kilogram of CIS43LS and underwent controlled human malaria infection approximately 36 weeks later had no parasitemia, with serum concentrations of CIS43LS of 46 and 57 μg per milliliter at the time of controlled human malaria infection.
CONCLUSIONS
Among adults who had never had malaria infection or vaccination, administration of the long-acting monoclonal antibody CIS43LS prevented malaria after controlled infection. (Funded by the National Institute of Allergy and Infectious Diseases; VRC 612 ClinicalTrials.gov number, NCT04206332.).
背景
需要额外的干预措施来降低疟疾引起的发病率和死亡率。
方法
我们进行了一项两部分、1 期临床试验，以评估具有延长半衰期的抗疟单克隆抗体 CIS43LS 的安全性和药代动力学及其对感染的疗效。试验的第 A 部分评估了从未感染过疟疾的健康成年人皮下或静脉内给予 CIS43LS 的安全性、初始副作用谱和药代动力学。参与者以三种递增剂量水平之一接受 CIS43LS 治疗。第 A 部分的一部分参与者继续进入第 B 部分，其中一些人接受了第二次 CIS43LS 输注。第 B 部分招募了更多参与者，并接受了静脉内 CIS43LS。为了评估 CIS43LS 的保护效力，一些参与者接受了受控的人体疟疾感染，在给予 CIS43LS 后 4 至 36 周，他们暴露于携带疟原虫孢子的蚊子中。
结果
共有 25 名参与者接受了 5 毫克/千克、20 毫克/千克或 40 毫克/千克的 CIS43LS 剂量，其中 4 名参与者接受了第二次剂量（无论初始剂量如何，均为 20 毫克/千克）。未发现安全问题。我们观察到 CIS43LS 血清浓度随剂量增加而增加，半衰期为 56 天。与未接受 CIS43LS 的 6 名对照参与者中的 5 名相比，接受 CIS43LS 的 9 名参与者中的 1 名都没有根据聚合酶链反应检测到寄生虫血症，直至受控人体疟疾感染后 21 天。接受 CIS43LS 40 毫克/千克的 2 名参与者在大约 36 周后再次接受受控人体疟疾感染，没有寄生虫血症，在受控人体疟疾感染时 CIS43LS 的血清浓度分别为 46 和 57 μg/ml。
结论
在从未感染过疟疾或接种过疫苗的成年人中，给予长效单克隆抗体 CIS43LS 可预防受控感染后的疟疾。（由美国国立过敏和传染病研究所资助；VRC 612 临床试验.gov 编号，NCT04206332。）
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