A structure-guided study of the circumsporozoite protein highlight common targets for antibody binding.

May 1, 2024

Each year, approximately 240 million cases of malaria are projected to occur worldwide. Most treatments for malaria are cost-prohibitive for broad use or provided as symptomatic care. Recent groundbreaking antimalarial vaccines promise to reduce this trend, but suffer from requiring multiple booster doses and limited effectiveness on different types of malaria. Developing a broad spectrum affordable malaria vaccine would have huge humanitarian and economic benefits.

In this work, Thai et al. studied the monoclonal antibodies which showed high potency against the malarial parasite P. falciparum. By comparing multiple circumsporozoite protein structures, a series of common loop motifs each antibody were identified. Differences in the in vitro efficacy of various antibodies were related to differences in how, which, and how many, epitopes were being recognized for each antibody. The results provide further opportunity to engineer novel antibodies with increased potency and/or polyvalent vaccine design.

PDB: 8FB5 (+ 18 more)

Article: Thai, Elaine, et al. "Molecular determinants of cross-reactivity and potency by VH3-33 antibodies against the Plasmodium falciparum circumsporozoite protein." Cell Reports 42.11 (2023).