Title

Blocking Borrelia burgdorferi transmission from infected ticks to nonhuman primates with a human monoclonal antibody

UMMS Affiliation

MassBiologics

Publication Date

2021-06-01

Document Type

Article

Disciplines

Bacterial Infections and Mycoses | Immunology of Infectious Disease | Immunoprophylaxis and Therapy | Infectious Disease

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.

Keywords

Bacterial infections, Bacterial vaccines, Immunology, Infectious disease

DOI of Published Version

10.1172/JCI144843

Source

Schiller ZA, Rudolph MJ, Toomey JR, Ejemel M, LaRochelle A, Davis SA, Lambert HS, Kern A, Tardo AC, Souders CA, Peterson E, Cannon RD, Ganesa C, Fazio F, Mantis NJ, Cavacini LA, Sullivan-Bolyai J, Hu LT, Embers ME, Klempner MS, Wang Y. Blocking Borrelia burgdorferi transmission from infected ticks to nonhuman primates with a human monoclonal antibody. J Clin Invest. 2021 Jun 1;131(11):e144843. doi: 10.1172/JCI144843. PMID: 33914704; PMCID: PMC8159683. Link to article on publisher's site

Journal/Book/Conference Title

The Journal of clinical investigation

Comments

Full author list omitted for brevity. For the full list of authors, see article.

Related Resources

Link to Article in PubMed

PubMed ID

33914704

Share

COinS