Developing 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 a prevalent tick-borne illness in the Northern Hemisphere.
• Currently, no approved human vaccines exist for LD, highlighting a critical unmet medical need.
• Rational adjuvant selection offers a systematic approach to developing effective and safe vaccine regimens.

Purpose of the Study:

• To evaluate the efficacy of a novel Lyme disease vaccine antigen (CspZ-YAC187S) formulated with different human-compatible adjuvants.
• To analyze the immunomodulatory mechanisms elicited by various adjuvant combinations.
• To identify a vaccine strategy that induces durable protective immunity against Borrelia burgdorferi.

Main Methods:

• Formulation of the CspZ-YAC187S antigen with selected adjuvants.
• Transcriptomic analysis to investigate adjuvant-mediated immunomodulation.
• Assessment of vaccine efficacy through Borrelia burgdorferi challenge studies.
• Quantification of antibody titers and immune cell responses, including IgG1 memory cells.

Main Results:

• Alum-CpG and Alum-αGal formulations elicited high titers of protective antibodies against CspZ-YAC187S.
• Alum-CpG formulated vaccine provided up to nine months of protective bactericidal antibody titers.
• Immunity was characterized by robust recall-memory responses and elevated IgG1 memory cells, indicating durable protection.

Conclusions:

• Rational adjuvant selection identified Alum-CpG as a promising adjuvant for a Lyme disease vaccine.
• The Alum-CpG formulation induces durable, memory immunity, crucial for preventing Lyme disease.
• This study advances understanding of adjuvant mechanisms and paves the way for developing effective Lyme disease vaccines.