Development of Pre-Erythrocytic Malaria Vaccines and antibodies

前红细胞疟疾疫苗和抗体的开发

• 批准号: 10497744
• 负责人: ROBERT A SEDER
• 金额: $ 105.64万
• 依托单位: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10497744
• 关键词: Adjuvant; Animal Model; Antibodies; Area; Attenuated; Blood; Blood Cells; Clinical Trials; Development; Drug Kinetics; Epitopes; Erythrocytes; Formulation; Goals; Half-Life; Human; Imaging Techniques; Immune; Immunity; Immunologic Adjuvants; Infant; Infection; Kenya; Liver; Malaria; Malaria Vaccines; Minor; Modeling; Monoclonal Antibodies; Mus; Mutation; Phase I Clinical Trials; Phase II Clinical Trials; Prevention; Proteins; Route; Safety; Site; Sporozoites; T-Lymphocyte; Testing; Vaccinated; Vaccine Design; Vaccines; Yeasts; circumsporozoite protein; comparative; efficacy evaluation; human monoclonal antibodies; immunogenicity; improved; in vivo; in vivo Model; in vivo imaging; malaria infection; neutralizing monoclonal antibodies; nonhuman primate; novel vaccines; prevent; vaccine-induced antibodies

The major discovery this year are as follows. 1. Completed immune and efficacy analysis of a phase II clinical trial in Kenya in 5-12 month infants to assess whether irradiated PfSPZ given by the IV route is safe, and confers durable immunity and protection against natural exposure. 2. Increased the half-life of mAb CIS43 by introducing an LS mutation in the Fc region. CIS43LS was shown to have comparable protection in vivo as CIS43 but have significantly longer half-life in non-human primates. 2. Initiated a Phase I clinical trial for mAB CIS 43LS against the junctional region of PfCSP for safety, pharmacokinetics and protection against controlled human malaria infection. 4. Isolated a new human mAb, L9, which defined a new distinct epitope comprising the minor and major repeats of PfCSP. 5. Comparative analysis of the in vivo potency of L9 against a number of human mAbs against CSP. Elucidated in vivo mechanisms of these antibodies demonstrating that several of them limit infection in the liver. 6. Developed in vivo imaging techniques to model the interaction between antibodies and sporozoites in mice.

今年的主要发现如下。