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Vaccinations01:51

Vaccinations

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Develop a durable, memory-driven, CspZ-targeting Lyme disease vaccine by rationale adjuvant selection.

Miranda McCarty1, Sergio A Hernández1,2, Jill Malfetano3

  • 1Department of Infectious Disease and Global Health, Cummings School of Veterinary Medicine, Tufts University, North Grafton, MA, USA.

Biorxiv : the Preprint Server for Biology
|January 16, 2026
PubMed
Summary

Developing a Lyme disease vaccine, researchers identified Alum-CpG and Alum-αGal adjuvants that enhance protective antibodies and immunity against Borrelia burgdorferi (Bb) infection.

Keywords:
AdjuvantBorreliaCspZLyme diseaseVaccine

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Area of Science:

  • Vaccinology
  • Immunology
  • Infectious Diseases

Background:

  • Lyme disease (LD), caused by Borrelia burgdorferi (Bb), is the most common tick-borne illness in the Northern Hemisphere.
  • Currently, no effective vaccines are available for Lyme disease, highlighting the need for novel vaccine strategies.
  • Rational adjuvant selection offers a systematic approach to developing safe and effective vaccine regimens.

Purpose of the Study:

  • To identify optimal adjuvants for a previously developed Lyme disease vaccine antigen, CspZ-YAC187S.
  • To analyze the immunomodulatory mechanisms elicited by different adjuvant formulations.
  • To evaluate the efficacy of the formulated vaccines against *Bb* infection.

Main Methods:

  • Formulation of the CspZ-YAC187S antigen with various human-compatible adjuvants.
  • Transcriptomic analysis to characterize immune responses.
  • Assessment of vaccine efficacy through challenge with *Bb* infection.

Main Results:

  • Alum-CpG and Alum-αGal adjuvants induced the highest titers of CspZ-YAC187S-specific protective antibodies.
  • Both Alum-CpG and Alum-αGal formulations demonstrated robust protection against *Bb* infection via distinct immunomodulatory pathways.
  • Alum-CpG formulated vaccine provided sustained bactericidal antibody titers for up to nine months and induced a recall-memory response.

Conclusions:

  • The study identified Alum-CpG as a promising adjuvant for a durable, memory immunity-driven Lyme disease vaccine.
  • The findings underscore the potential of rational adjuvant selection in optimizing vaccine development for infectious diseases.
  • This research contributes to understanding adjuvant-mediated immune responses for future vaccine design against Lyme disease.