Potent antibody lineage against malaria transmission elicited by human vaccination with Pfs25

• Published in: Nature communications Vol. 10; no. 1; pp. 4328 - 11
• Main Authors: McLeod, Brandon, Miura, Kazutoyo, Scally, Stephen W., Bosch, Alexandre, Nguyen, Ngan, Shin, Hanjun, Kim, Dongkyoon, Volkmuth, Wayne, Rämisch, Sebastian, Chichester, Jessica A., Streatfield, Stephen, Woods, Colleen, Schief, William R., Emerling, Daniel, King, C. Richter, Julien, Jean-Philippe
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 24.09.2019; Nature Publishing Group; Nature Portfolio
• Subjects: 101/1; 14/63; 49/23; 631/250/2152/2153/1291; 631/250/590; 631/535/1266; 692/699/255/1629; Antibodies, Protozoan - chemistry; Antibody Formation; Aquatic insects; Binding Sites, Antibody; Blocking antibodies; Crystallography; Crystallography, X-Ray; Disease transmission; Epitopes; Human behavior; Humanities and Social Sciences; Humans; Immunization; Immunogenicity; Immunoglobulins; Malaria; Malaria Vaccines - therapeutic use; Malaria, Falciparum - prevention & control; Malaria, Falciparum - transmission; Molecular modelling; Monoclonal antibodies; Mosquitoes; multidisciplinary; Parasites; Plasmodium falciparum; Protozoan Proteins - chemistry; Protozoan Proteins - immunology; Science; Science (multidisciplinary); Vaccines; Vector-borne diseases
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-019-11980-6

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. Pfs25 is a transmission-blocking vaccine candidate for Plasmodium . Here, McLeod et al. analyze the antibody response to Pfs25 in sera from a clinical trial evaluating a Pfs25 vaccine candidate, identify a potent transmission-blocking antibody and determine recognized epitopes on Pfs25.