PDBsum entry 6phh

Immune system

PDB id: 6phh

Contents

Protein chains

228 a.a.

217 a.a.

Ligands

GOL ×6

Waters ×124

PDB id:

6phh

Name:

Immune system

Title:

Unliganded human transmission blocking antibody 2544

Structure:

2544 antibody fab, heavy chain. Chain: c, a. Engineered: yes. 2544 antibody fab, light chain. Chain: d, b. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Expressed in: homo sapiens. Expression_system_taxid: 9606. Expression_system_taxid: 9606

Resolution:

2.40Å R-factor: 0.219 R-free: 0.249

Authors:

B.R.Mcleod,J.P.Julien

Key ref:

B.McLeod et al. (2019). Potent antibody lineage against malaria transmission elicited by human vaccination with Pfs25. Nat Commun, 10, 4328. PubMed id: 31551421 DOI: 10.1038/s41467-019-11980-6

Date:

25-Jun-19 Release date: 02-Oct-19

Protein chains

No UniProt id for this chain

Struc: 228 a.a.

Protein chains

No UniProt id for this chain

Struc: 217 a.a.

DOI no: 10.1038/s41467-019-11980-6

Nat Commun 10:4328 (2019)

PubMed id: 31551421

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

B.McLeod, K.Miura, S.W.Scally, A.Bosch, N.Nguyen, H.Shin, D.Kim, W.Volkmuth, S.Rämisch, J.A.Chichester, S.Streatfield, C.Woods, W.R.Schief, D.Emerling, C.R.King, J.P.Julien.

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.