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Rickettsia rickettsii outer membrane protein YbgF induces protective immunity in C3H/HeN mice
Wenping Gong1, Yong Qi, Xiaolu Xiong
1a State Key Laboratory of Pathogen and Biosecurity; Beijing Institute of Microbiology and Epidemiology ; Fengtai , Beijing , China.
Abstract:
Rickettsia rickettsii is the etiological agent of Rocky Mountain spotted fever (RMSF). YbgF and TolC are outer membrane-associated proteins of R. rickettsii that play important roles in its interaction with host cells. We investigated the immunogenicity of YbgF and TolC for protection against RMSF. We immunized C3H/HeN mice with recombinant R. rickettsii YbgF (rYbgF) or TolC (rTolC). Rickettsial burden and impairment in the lungs, spleens, and livers of rYbgF-immunized mice were significantly lower than in rTolC-immunized mice. The ratio of IgG2a to IgG1 in rYbgF-immunized mice continued to increase over the course of our experiments, while that in rTolC-immunized mice was reduced. The proliferation and cytokine secretion of CD4(+) and CD8(+) T cells isolated from R. rickettsii-infected mice were analyzed following antigen stimulation. The results indicated that proliferation and interferon (IFN)-γ secretion of CD4(+) or CD8(+) T cells in R. rickettsii-infected mice were significantly greater than in uninfected mice after stimulation with rYbgF. YbgF is a novel protective antigen of R. rickettsii. Protection conferred by YbgF is dependent upon IFN-γ-producing CD4(+) and CD8(+) T cells and IgG2a, which act in synergy to control R. rickettsii infection.
Insights
YbgF is a novel protective antigen against Rocky Mountain spotted fever (RMSF). Immunization with YbgF significantly reduced Rickettsia rickettsii burden and enhanced T cell responses, offering a promising vaccine candidate.
Area of Science:
- Microbiology
- Immunology
- Vaccinology
Background:
- Rickettsia rickettsii causes Rocky Mountain spotted fever (RMSF).
- Outer membrane proteins YbgF and TolC are involved in R. rickettsii host cell interactions.
- Investigating immunogenic proteins for RMSF vaccine development is crucial.
Purpose of the Study:
- To evaluate the immunogenicity of R. rickettsii YbgF and TolC proteins for protection against RMSF.
- To determine the role of T cells and antibody responses in YbgF-mediated protection.
Main Methods:
- Mice were immunized with recombinant YbgF (rYbgF) or TolC (rTolC).
- Rickettsial burden in organs was assessed post-infection.
- Antibody isotypes (IgG2a/IgG1 ratio) and T cell responses (proliferation, cytokine secretion) were analyzed.
Main Results:
- rYbgF immunization significantly reduced rickettsial burden and organ impairment compared to rTolC.
- YbgF induced a higher IgG2a to IgG1 ratio, indicating a Th1-biased immune response.
- rYbgF stimulation enhanced proliferation and IFN-γ secretion in CD4+ and CD8+ T cells.
Conclusions:
- YbgF is a novel protective antigen for R. rickettsii.
- Protection against RMSF by YbgF is mediated by IFN-γ-producing T cells and IgG2a antibodies.
- YbgF represents a promising candidate for RMSF vaccine development.
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