Targeting Bottlenecks in Malaria Transmission: Antibody‐Epitope Descriptions Guide the Design of Next‐Generation Biomedical Interventions

Immunological Reviews, Год журнала: 2025, Номер 330(1)

Опубликована: Фев. 5, 2025

ABSTRACT Malaria continues to pose a significant burden global health. Thus, strong need exists for the development of diverse panel intervention strategies and modalities combat malaria achieve elimination eradication goals. Deploying interventions that target bottlenecks in transmission life cycle causative agent malaria, Plasmodium parasites, is an attractive strategy. The highly potent antibody‐based biologics, including vaccines, can be greatly facilitated by in‐depth molecular understanding antibody‐epitope interactions. Here, we provide overview structurally characterized antibodies targeting lead vaccine candidates expressed during which include pre‐erythrocytic sexual stages. repeat region circumsporozoite protein (CSP), domain 1 Pfs230 domains 3 Pfs48/45 are critical regions targeted most at two transmission, with other promising targets emerging requiring further characterization.

Язык: Английский

Virus-like particle vaccines targeting a key epitope in circumsporozoite protein provide sterilizing immunity against malaria in a mouse challenge model

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2025, Номер unknown

Опубликована: Март 11, 2025

Vaccines that target the pre-erythrocytic stage of malaria lifecycle have potential to provide sterilizing immunity but must elicit sustained, high-titer antibody responses completely prevent infection. Most vaccines circumsporozoite protein (CSP), major surface antigen on Plasmodium falciparum sporozoites. Antibodies targeting distinct epitopes within central repeat region CSP protection from infection, we focused developing a highly vulnerable epitope is targeted by potent monoclonal L9. In previous study, produced vaccine displaying synthetic peptide representing L9 Qβ bacteriophage virus-like particles (VLPs). This elicited strong anti-CSP protected mice challenge. Here, asked whether structural context influences quality responses. We compared immunogenicity and protective efficacy VLPs recombinant display in structure hypothesized mimic its native conformation. Recombinant MS2 various lengths were evaluated mice. Our results demonstrate VLPs, particularly those longer peptides combination with novel adjuvant, durable lower liver burden also L9-targeted licensed vaccine, RTS,S/AS01 E (Mosquirix™, GSK). Immunization provided significant liver-stage infection mouse model; immunization highest percentage A consisting each presenting forms, strongest protection, reducing parasite promoting more effectively than vaccine.

Язык: Английский

Having your cake and eating it too – a new target for sporozoite-neutralising mAbs

Trends in Parasitology, Год журнала: 2025, Номер unknown

Опубликована: Фев. 1, 2025

Язык: Английский