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Title:Developing a durable, memory-driven, CspZ-targeting Lyme disease vaccine by rationale adjuvant selection
Authors:ID McCarty, Miranda (Author)
ID Hernández, Sergio A. (Author)
ID Malfetano, Jill (Author)
ID Leão, Ana Carolina (Author)
ID Villar, Maria Jose (Author)
ID Yang, Xiuli (Author)
ID Chen, Yi-Lin (Author)
ID Lee, Jungsoon (Author)
ID Liu, Zhuyun (Author)
ID Strych, Ulrich (Author)
ID Strle, Klemen (Author), et al.
Files:.pdf PDF - Presentation file, download (3,12 MB)
MD5: FA1854E1DBFB4DC086339B4A21BC11A6
 
URL URL - Source URL, visit https://www.nature.com/articles/s41541-026-01482-0
 
Language:English
Typology:1.01 - Original Scientific Article
Organization:Logo UKC LJ - Ljubljana University Medical Centre
Abstract:Rational adjuvant selection is a systematic approach based on adjuvant-mediated immunomodulation to identify safe vaccine regimens that enhance protective immunity. Transmitted through ticks and caused by the bacterium Borrelia burgdorferi (Bb), Lyme disease (LD) is the most common vector-borne disease in the Northern hemisphere. There are no approved human vaccines, making it suitable for testing the concept of rational adjuvant selection. Here, we formulated our previously developed and effective LD vaccine antigen, CspZ-YAC187S, with different adjuvants suitable for human use; we analyzed the immune response by transcriptomics and tested the vaccine efficacy after Bb infection. We identified Alum-CpG and Alum-αGal to elicit the highest titers of CspZ-YAC187S-dependent protective antibodies and robust levels of protection, but through distinct mechanisms of immunomodulation. We demonstrated that immunization with Alum-CpG formulated CspZ-YAC187S provided up to nine months of protective bactericidal antibody titers, as well as recall-memory response to prevent LD after natural infection. Immunity was linked to elevated levels of IgG1 memory cells in the vaccine-triggered immune responses. This work thus identified a durable, memory immunity-driven LD vaccine, ultimately paving the road to understand the mechanisms of rationale adjuvant selection for vaccine development.
Keywords:Lyme disease, Lyme disease vaccine, immunization
Publication status:Published
Publication version:Version of Record
Year of publishing:2026
Number of pages:str. 1-15
Numbering:Vol. 11, article no. ǂ168
PID:20.500.12556/DiRROS-31917 New window
UDC:616.9
ISSN on article:2059-0105
DOI:10.1038/s41541-026-01482-0 New window
COBISS.SI-ID:279895043 New window
Note:Nasl. z nasl. zaslona; Opis vira z dne 29. 5. 2026;
Publication date in DiRROS:18.08.2026
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Downloads:28
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Record is a part of a journal

Title:npj vaccines
Publisher:Springer Nature
ISSN:2059-0105
COBISS.SI-ID:526077721 New window

Document is financed by a project

Funder:NIH - National Institutes of Health
Project number:1R01AI181746-01
Name:Immunomodulatory mechanisms of wild bird reservoir hosts that facilitate persistence of Lyme disease bacteria

Funder:NIH - National Institutes of Health
Project number:1R01AI181904-01
Name:Microbial Determinants of Excessive Inflammation and Severe Lyme Disease

Funder:NIH - National Institutes of Health
Project number:1R01AI154542-01
Name:Multivalent Tick-Microbe targeted Lyme disease vaccines

Funder:NIH - National Institutes of Health
Project number:1R21AI144891-01A1
Name:Identification of the mechanism of protection against a B. burgdorferi protein CspZ for the prevention of Lyme disease

Funder:Other - Other funder or multiple funders
Funding programme:U. S. Department of Defense
Project number:W81XWH-20-1-0913
Name:/

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License:CC BY-NC-ND 4.0, Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International
Link:http://creativecommons.org/licenses/by-nc-nd/4.0/
Description:The most restrictive Creative Commons license. This only allows people to download and share the work for no commercial gain and for no other purposes.

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