Journal Article

Protective properties of a candidate C-terminal domain OspA vaccine for prevention of Lyme disease

Singh, Guy, Park, Jeong-Jin, Fritzer, Andrea, Bartuschka, Ursula, Embers, Monica E., Li, Yan, Timofeyeva, Yekaterina, Gribenko, Alexey, Lundberg, Urban, Simon, Raphael, Esadze, Alexandre, Seidel, Stefan, Tardo, Amanda C., Dane, Jill, Jost, Sandra, Hasenkampf, Nicole R., Sun, Jun, Anderson, Annaliesa S., Wellnitz, Sabine, Giordano-Schmidt, Donna, Tran, Sirena, Gaylord, Michelle, Kanevsky, Isis, Kalina, Warren, Hochreiter, Romana, Meinke, Andreas, Baranova, Danielle

2026

Overview

Lyme disease is a growing public health concern that is geographically focused in regions where ticks that carry the causative bacteria, Borrelia burgdorferi sensu lato (s.l.), are endemic. Outer surface protein A (OspA) is expressed by B. burgdorferi s.l. spirochetes during the tick phase and OspA antibodies introduced during tick feeding can block transmission and prevent B. burgdorferi infection. Candidate Lyme disease vaccine VLA15 is comprised of the C-terminal domains of the six B. burgdorferi s.l. OspA serotypes (ST) prevalent in North America and Europe. We report herein that non-human primates immunized with VLA15 were protected against challenge with Ixodes scapularis ticks bearing B. burgdorferi sensu stricto (s.s.) (OspA ST1). Levels of residual B. burgdorferi s.s. tick colonization were reduced in ticks that fed on VLA15-immunized primates compared to those immunized with full length-OspA ST1 (FL-OspA) at a point when OspA-binding IgG levels were similar. Furthermore, monoclonal antibodies targeting the C-terminal half of OspA, elicited by FL-OspA immunization in primates, were more effective at complement-mediated bactericidal killing in vitro and clearance of spirochetes in ticks versus those directed against other parts of the protein. •VLA15 immunization protected NHPs against challenge with Ixodes ticks bearing B. burgdorferi ss (OspA ST1).•Post-challenge tick colonization levels were reduced in VLA15-immunized NHPs compared to levels in FL-OspA-immunized NHPs, despite similar anti-OspA IgG levels between the two vaccine groups.•Monoclonal antibodies targeting the C-terminal and central domains of OspA ST1 bound cell-associated OspA and manifested greater functional activity in vitro, and in vivo in mice challenged with Ixodes ticks bearing B. burgdorferi ss.

• Publisher: Elsevier Ltd,Elsevier Limited
• Subject: Allergy and Immunology / Aluminum / amino acid sequences / Animals / Antibodies, Bacterial - blood / Antibodies, Bacterial - immunology / Antibodies, Monoclonal - immunology / Antibody / Antigens, Surface - immunology / Arachnids / Bacterial Outer Membrane Proteins - immunology / Bacterial Vaccines - administration & dosage / Bacterial Vaccines - immunology / Borrelia burgdorferi / Borrelia burgdorferi - immunology / Chromatography / complement / Complement system / E coli / Europe / Female / Females / Immunization / Immunoglobulin G / Immunoglobulin G - blood / Infections / Ixodes - microbiology / Ixodes scapularis / Laboratory animals / Lipoproteins - immunology / Lyme disease / Lyme Disease - immunology / Lyme Disease - prevention & control / Lyme Disease Vaccines - immunology / Monoclonal antibodies / Non-human primate / North America / OspA / OspA protein / Outer surface protein A / Pathogens / Primates / Protein A / Proteins / Public health / Serotypes / Spirochetes / Surface protein A / surface proteins / Ticks / Vaccine / Vaccines / Vector-borne diseases / Veterinarians