美国疫苗研究中心Robert A. Seder团队研究了一种单克隆抗体预防疟疾的效果。2021年8月11日出版的《新英格兰医学杂志》发表了这项成果。

目前需要采取更多的干预措施来降低疟疾造成的发病率和死亡率。

研究组进行了一项两部分的1期临床试验，以评估CIS43LS（一种半衰期延长的抗疟单克隆抗体）的安全性和药代动力学，以及它对恶性疟原虫感染的有效性。该试验的A部分评估了CIS43LS在从未患过疟疾的健康成人中的安全性、初始副作用和药代动力学。参与者接受CIS43LS皮下或静脉注射，剂量为三个递增剂量水平之一。

来自A部分的一些参与者继续参与B部分，一些人接受了第二次CIS43LS注射。其他参与者被纳入B部分，并接受静脉注射CIS43LS。为了评估CIS43LS的保护效力，一些参与者在注射CIS43LS 4至36周后暴露于携带恶性疟原虫孢子虫的蚊子，并进行受控人类疟疾感染。

共有25名参与者接受了CIS43LS，剂量分别为每公斤体重5毫克、20毫克或40毫克，25名参与者中有4名接受了二次剂量（无论初始剂量如何，每公斤体重20毫克）。没有发现任何安全隐患。研究人员观察到CIS43LS血清浓度呈剂量依赖性增加，半衰期为56天。

根据聚合酶链反应试验，在受控人类疟疾感染21天后，接受CIS43LS的9名参与者没有出现寄生虫血症，而在没有接受CIS43LS的6名对照组参与者中有5人出现寄生虫血症。两名参与者接受了每公斤体重40毫克的CIS43LS，大约36周后接受了受控人类疟疾感染，没有出现寄生虫血症；在受控人类疟疾感染时，CIS43LS的血清浓度分别为46和57 μg/mL。

研究结果表明，在从未感染过疟疾或从未接种过疟疾疫苗的成年人中，使用长效单克隆抗体CIS43LS可在受控感染后有效预防疟疾。

附：英文原文

Title: A Monoclonal Antibody for Malaria Prevention

Author: Martin R. Gaudinski, M.D.,, Nina M. Berkowitz, M.P.H.,, Azza H. Idris, M.D., Ph.D.,, Emily E. Coates, Ph.D.,, LaSonji A. Holman, F.N.P.,, Floreliz Mendoza, R.N.,, Ingelise J. Gordon, R.N.,, Sarah H. Plummer, M.S.N., C.R.N.P.,, Olga Trofymenko, M.D.,, Zonghui Hu, Ph.D.,, Andrezza Campos Chagas, Ph.D.,, Sarah O’Connell, M.S.,, Manjula Basappa, B.S.,, Naomi Douek,, Sandeep R. Narpala, M.S.,, Christopher R. Barry, M.S.,, Alicia T. Widge, M.D., M.S.,, Renunda Hicks,, Seemal F. Awan, M.D.,, Richard L. Wu, M.D.,, Somia Hickman, Ph.D.,, Diane Wycuff, Ph.D.,, Judy A. Stein, M.B.A.,, Christopher Case, Ph.D.,, Brian P. Evans, Ph.D.,, Kevin Carlton, M.S.,, Jason G. Gall, Ph.D.,, Sandra Vazquez, M.S.,, Britta Flach, Ph.D.,, Grace L. Chen, M.D.,, Joseph R. Francica, Ph.D.,, Barbara J. Flynn, M.S.,, Neville K. Kisalu, Ph.D.,, Edmund V. Capparelli, Pharm.D.,, Adrian McDermott, Ph.D.,, John R. Mascola, M.D.,, Julie E. Ledgerwood, D.O.,, and Robert A. Seder, M.D.

Issue&Volume: 2021-08-11

Abstract:

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 Plasmodium falciparum. 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 P. falciparum 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.

DOI: 10.1056/NEJMoa2034031

Source: https://www.nejm.org/doi/full/10.1056/NEJMoa2034031