Testing the capacity of humanized immune system mice to induce a protective antibody response against the Lyme disease pathogen

antigen that proved efficacious not only as part of licensed canine vaccines but also as part of a human LD vaccine that was transiently available to the public in the past. The data demonstrated that the tested models could not clear the ∆VlsE infection. Likewise, OspA-vaccinated humanized mouse immune system failed to prevent wild-type challenge. Given that no better alternative preclinical model has been developed, we hope that the inherent translatability limitations of standard LD mouse models will continue to be favorably accepted. Although our results do not encourage the use of the tested humanized models for preclinical LD vaccine efficacy testing, their utility remains valuable for mechanistic studies. IMPORTANCE: . In contrast to an intact mouse immune system of classical LD models, the humanized immune system could not prevent vaccinated mice from being infected with LD spirochetes. The findings demonstrate that two tested humanized models cannot be used for preclinically testing LD vaccine candidates. Given the results, we hope that the animal-to-human translatability limitations of existing LD mouse models will be more favorably taken as there is no better alternative preclinical model developed.