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

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-YA_C187S.
• 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-YA_C187S 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-YA_C187S-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.