6PHC

Pfs25 in complex with the human transmission blocking antibody 2544

Summary for 6PHC

• Entry DOI: 10.2210/pdb6phc/pdb
• Related: 6PHB
• Descriptor: 25 kDa ookinete surface antigen, 2544 Antibody Fab, Heavy Chain, 2544 Antibody Fab, Light Chain, ... (4 entities in total)
• Functional Keywords: fab, complex, antigen, immunoglobulin, immune system
• Biological source: Plasmodium falciparum; More
• Total number of polymer chains: 6
• Total formula weight: 137424.51

Authors

McLeod, B.R.,Julien, J.P. (deposition date: 2019-06-25, release date: 2019-10-02, Last modification date: 2024-10-16)

Primary citation

McLeod, B.,Miura, K.,Scally, S.W.,Bosch, A.,Nguyen, N.,Shin, H.,Kim, D.,Volkmuth, W.,Ramisch, S.,Chichester, J.A.,Streatfield, S.,Woods, C.,Schief, W.R.,Emerling, D.,King, C.R.,Julien, J.P.
Potent antibody lineage against malaria transmission elicited by human vaccination with Pfs25.
Nat Commun, 10:4328-4328, 2019

PubMed Abstract: Transmission-blocking vaccines have the potential to be key contributors to malaria elimination. Such vaccines elicit antibodies that inhibit parasites during their development in Anopheles mosquitoes, thus breaking the cycle of transmission. To date, characterization of humoral responses to Plasmodium falciparum transmission-blocking vaccine candidate Pfs25 has largely been conducted in pre-clinical models. Here, we present molecular analyses of human antibody responses generated in a clinical trial evaluating Pfs25 vaccination. From a collection of monoclonal antibodies with transmission-blocking activity, we identify the most potent transmission-blocking antibody yet described against Pfs25; 2544. The interactions of 2544 and three other antibodies with Pfs25 are analyzed by crystallography to understand structural requirements for elicitation of human transmission-blocking responses. Our analyses provide insights into Pfs25 immunogenicity and epitope potency, and detail an affinity maturation pathway for a potent transmission-blocking antibody in humans. Our findings can be employed to guide the design of improved malaria transmission-blocking vaccines.

PubMed: 31551421
DOI: 10.1038/s41467-019-11980-6

Experimental method

X-RAY DIFFRACTION (2.9 Å)