An immunogen and vaccine for generating immunity to Borrelia burgdorferi, including a vaccine for Lyme disease.
This invention relates to a composition and method for generating immunity. Disclosed is an immunogen including modified CspZ or portions of modified CspZ from Borrelia burgdorferi. In some examples, the immunogen also includes bacteriophage Q β-derived VLP. The modified CspZ may be modified to not bind FH or to bind FH minimally, weakly, or transiently. Inoculation with a vaccine including such an immunogen induces antibodies that may efficiently eradicate spirochetes in vitro and prevents Lyme-associated arthritis and tissue colonization in vivo.
Findings suggest that CspZ allows spirochete to survive in the blood and disseminate to different tissues during infection. cspZ expression is detectable when spirochetes are in mammalian hosts and in vitro cultivation, and inoculating mice with CspZ triggers antibody response against this protein. Although whether all isolates from Lyme disease borreliae species encode cspZ is still unclear, the isolates from B. burgdorferi (North American species of Lyme disease spirochetes) and the European Lyme disease borreliae strains that cause severe systemic infection all carry this gene (Rogers et al., 2007). The cspZ alleles among these Lyme borreliae isolates were grouped into three types and share more than 70% of sequence identity (Rogers et al., 2009; Rogers et al., 2007). These observations suggest that CspZ may have vaccinogenic potential by inducing antibody-mediated bactericidal activity against B. burgdorferi.
However, immunization with CspZ does not protect mice from infection (Coleman et al., 2008), raising a possibility that CspZ as a vaccine does not induce antibody titers robust enough to kill B. burgdorferi. The present disclosure is directed to overcoming these and other deficiencies in conventional technologies.
- Longer lasting protection
- cspZ is highly conserved among Lyme borrelia strains (.80% sequence identity) and carried in all B. burgdorferi and B. afzelii strains isolated from human patients with systemic and more severe manifestations.
- Prevents Lyme-associated arthritis and tissue colonization in-vivo.
Patents and Licensing:
“Composition and Method for Generating Immunity to Borrelia Burgdorferi”
Marcinkiewicz Ashley L., Lieknina Ilva, Kotelovica Svetlana, Yang Xiuli, Kraiczy Peter, Pal Utpal, Lin Yi-Pin, Tars Kaspars. Frontiers in Immunology Volume 9 2018 DOI=10.3389/fimmu.2018.00181 ISSN=1664-3224
Lin Yi-Pin, Frye Amber M., Nowak Tristan A., Kraiczy Peter Frontiers in Cellular and Infection Microbiology Volume 10 2020 DOI=10.3389/fcimb.2020.00001 ISSN=2235-2988
Marcinkiewicz AL, Lieknina I, Yang X, Lederman PL, Hart TM, Yates J, Chen WH, Bottazzi ME, Mantis NJ, Kraiczy P, Pal U, Tars K, Lin YP.Infect Immun. 2020 Apr 20;88(5):e00956-19. doi: 10.1128/IAI.00956-19. Print 2020 Apr 20. PMID: 32122944
Chen WH, Strych U, Bottazzi ME, Lin YP. Expert Rev Vaccines. 2022 Oct;21(10):1405-1417. doi: 10.1080/14760584.2022.2102484. Epub 2022 Jul 22. PMID: 35836340; PMCID: PMC9529901
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