7JWG

OspA-Fab 221-7 complex structure

Summary for 7JWG

• Entry DOI: 10.2210/pdb7jwg/pdb
• Descriptor: Antibody 221-7 Fab heavy chain, Antibody 221-7 Fab light chain, Outer surface protein A, ... (4 entities in total)
• Functional Keywords: ospa-fab complex, immune system
• Biological source: Homo sapiens; More
• Total number of polymer chains: 6
• Total formula weight: 146560.05

Authors

Rudolph, M.J. (deposition date: 2020-08-25, release date: 2021-09-08, Last modification date: 2024-11-20)

Primary citation

Schiller, Z.A.,Rudolph, M.J.,Toomey, J.R.,Ejemel, M.,LaRochelle, A.,Davis, S.A.,Lambert, H.S.,Kern, A.,Tardo, A.C.,Souders, C.A.,Peterson, E.,Cannon, R.D.,Ganesa, C.,Fazio, F.,Mantis, N.J.,Cavacini, L.A.,Sullivan-Bolyai, J.,Hu, L.T.,Embers, M.E.,Klempner, M.S.,Wang, Y.
Blocking Borrelia burgdorferi transmission from infected ticks to nonhuman primates with a human monoclonal antibody.
J.Clin.Invest., 131:-, 2021

PubMed Abstract: Disrupting transmission of Borrelia burgdorferi sensu lato complex (B. burgdorferi) from infected ticks to humans is one strategy to prevent the significant morbidity from Lyme disease. We have previously shown that an anti-OspA human mAb, 2217, prevents transmission of B. burgdorferi from infected ticks in animal models. Maintenance of a protective plasma concentration of a human mAb for tick season presents a significant challenge for a preexposure prophylaxis strategy. Here, we describe the optimization of mAb 2217 by amino acid substitutions (2217LS: M428L and N434S) in the Fc domain. The LS mutation led to a 2-fold increase in half-life in cynomolgus monkeys. In a rhesus macaque model, 2217LS protected animals from tick transmission of spirochetes at a dose of 3 mg/kg. Crystallographic analysis of Fab in complex with OspA revealed that 2217 bound an epitope that was highly conserved among the B. burgdorferi, B. garinii, and B. afzelii species. Unlike most vaccines that may require boosters to achieve protection, our work supports the development of 2217LS as an effective preexposure prophylaxis in Lyme-endemic regions, with a single dose at the beginning of tick season offering immediate protection that remains for the duration of exposure risk.

PubMed: 33914704
DOI: 10.1172/JCI144843

Experimental method

X-RAY DIFFRACTION (3.05 Å)