1. Evaluation of Lassa virus vaccine immunogenicity in a CBA/J-ML29 mouse model
- Author
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Goicochea, Marco A., Zapata, Juan C., Bryant, Joseph, Davis, Harry, Salvato, Maria S., and Lukashevich, Igor S.
- Subjects
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LASSA fever , *IMMUNIZATION , *PREVENTIVE medicine , *MORTALITY , *DRUG efficacy , *CELL-mediated cytotoxicity , *LABORATORY mice , *VACCINATION - Abstract
Abstract: Lassa fever (LF) is one of the most prevalent viral hemorrhagic fevers in West Africa responsible for thousands of deaths annually. The BSL-4 containment requirement and lack of small animal model to evaluate Lassa virus (LASV)-specific cell-mediated immunity (CMI) complicate development of effective LF vaccines. Here we have described a CBA/J-ML29 model allowing evaluation of LASV-specific CMI responses in mice. This model is based on Mopeia virus reassortant clone ML29, an attractive immunogenic surrogate for LASV. A single intraperitoneal (i.p.) immunization of CBA/J mice with ML29 protected animals against a lethal homologous intracerebral (i.c.) challenge with 588 LD50. The ML29-immunized mice displayed negligible levels of LASV-specific antibody titers, but LASV-specific CMI responses were detectable early and peaked on day 8–10 after immunization. A T cell cytotoxicity assay in vivo showed a correlation between LASV-specific cytotoxicity and the timing of protection induced by the ML29 immunization. Notably, CBA/J mice that received CD8+ T cell-depleted splenocytes from ML29-immunized donors all succumbed to a lethal i.c. challenge, demonstrating that CD8+ T cells are critical in protection. The CBA/J-ML29 model can be useful immunological tool for the preliminary evaluation of immunogenicity and efficacy of vaccine candidates against LASV outside of BSL-4 containment facilities. [Copyright &y& Elsevier]
- Published
- 2012
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