Vaccination-induced neutralizing antibodies in immunocompetent hosts correlate with protection against rickettsiae
Abstract We previously demonstrated that a single-dose immunization with a live-attenuated Rickettsia parkeri mutant 3A2 confers complete protection against murine spotted fever rickettsioses. In this study, we investigated whether vaccination-elicited serum antibodies serve as immune correlates of...
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Nature Portfolio
2025-08-01
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| Series: | npj Vaccines |
| Online Access: | https://doi.org/10.1038/s41541-025-01228-4 |
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| author | Loka Reddy Velatooru Jessica Plante Chen Yi Chu Garrett Cutchin Bing Zhu Nicole Burkhardt Carsen Roach Yingzi Cong Shahid Karim Yong-Fang Kuo David H. Walker Ulrike Munderloh Rong Fang |
| author_facet | Loka Reddy Velatooru Jessica Plante Chen Yi Chu Garrett Cutchin Bing Zhu Nicole Burkhardt Carsen Roach Yingzi Cong Shahid Karim Yong-Fang Kuo David H. Walker Ulrike Munderloh Rong Fang |
| author_sort | Loka Reddy Velatooru |
| collection | DOAJ |
| description | Abstract We previously demonstrated that a single-dose immunization with a live-attenuated Rickettsia parkeri mutant 3A2 confers complete protection against murine spotted fever rickettsioses. In this study, we investigated whether vaccination-elicited serum antibodies serve as immune correlates of protection against rickettsiae. Immunization of immunocompetent C3H/HeN mice with 3A2 induced a robust and durable level of IgG antibody response, predominantly comprising IgG2a, IgG3, and IgG2b subclasses, and was associated with a significant expansion of CD19+ CD45R+ IgDlow plasma cells. Compared to mock controls, passive transfer of immune sera from 3A2-immunized mice protected C3H-SCID mice from R. parkeri challenge via multiple inoculation routes, including i.v., i.d. and i.d. plus tick saliva. Strikingly, serum antibodies of 3A2-immunized mice significantly reduced the number of R. parkeri plaques in vitro, indicating direct neutralizing activity. Collectively, our findings demonstrate that vaccination-induced serum IgG antibodies correlate with protection against rickettsial infection and possess direct neutralizing effects on rickettsiae. |
| format | Article |
| id | doaj-art-d995860a5b7c430e9c06517e5f0eb8d7 |
| institution | Kabale University |
| issn | 2059-0105 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | npj Vaccines |
| spelling | doaj-art-d995860a5b7c430e9c06517e5f0eb8d72025-08-20T03:42:19ZengNature Portfolionpj Vaccines2059-01052025-08-0110111410.1038/s41541-025-01228-4Vaccination-induced neutralizing antibodies in immunocompetent hosts correlate with protection against rickettsiaeLoka Reddy Velatooru0Jessica Plante1Chen Yi Chu2Garrett Cutchin3Bing Zhu4Nicole Burkhardt5Carsen Roach6Yingzi Cong7Shahid Karim8Yong-Fang Kuo9David H. Walker10Ulrike Munderloh11Rong Fang12Department of Pathology, University of Texas Medical BranchDepartment of Microbiology and Immunology, University of Texas Medical BranchDepartment of Pathology, University of Texas Medical BranchDepartment of Pathology, University of Texas Medical BranchDepartment of Pathology, University of Texas Medical BranchDepartment of Entomology, University of MinnesotaDepartment of Pathology, University of Texas Medical BranchDepartment of Pathology, University of Texas Medical BranchSchool of Biological, Environmental, and Earth Sciences, University of Southern MississippiDepartment of Biostatistics & Data Science, University of Texas Medical BranchDepartment of Pathology, University of Texas Medical BranchDepartment of Entomology, University of MinnesotaDepartment of Pathology, University of Texas Medical BranchAbstract We previously demonstrated that a single-dose immunization with a live-attenuated Rickettsia parkeri mutant 3A2 confers complete protection against murine spotted fever rickettsioses. In this study, we investigated whether vaccination-elicited serum antibodies serve as immune correlates of protection against rickettsiae. Immunization of immunocompetent C3H/HeN mice with 3A2 induced a robust and durable level of IgG antibody response, predominantly comprising IgG2a, IgG3, and IgG2b subclasses, and was associated with a significant expansion of CD19+ CD45R+ IgDlow plasma cells. Compared to mock controls, passive transfer of immune sera from 3A2-immunized mice protected C3H-SCID mice from R. parkeri challenge via multiple inoculation routes, including i.v., i.d. and i.d. plus tick saliva. Strikingly, serum antibodies of 3A2-immunized mice significantly reduced the number of R. parkeri plaques in vitro, indicating direct neutralizing activity. Collectively, our findings demonstrate that vaccination-induced serum IgG antibodies correlate with protection against rickettsial infection and possess direct neutralizing effects on rickettsiae.https://doi.org/10.1038/s41541-025-01228-4 |
| spellingShingle | Loka Reddy Velatooru Jessica Plante Chen Yi Chu Garrett Cutchin Bing Zhu Nicole Burkhardt Carsen Roach Yingzi Cong Shahid Karim Yong-Fang Kuo David H. Walker Ulrike Munderloh Rong Fang Vaccination-induced neutralizing antibodies in immunocompetent hosts correlate with protection against rickettsiae npj Vaccines |
| title | Vaccination-induced neutralizing antibodies in immunocompetent hosts correlate with protection against rickettsiae |
| title_full | Vaccination-induced neutralizing antibodies in immunocompetent hosts correlate with protection against rickettsiae |
| title_fullStr | Vaccination-induced neutralizing antibodies in immunocompetent hosts correlate with protection against rickettsiae |
| title_full_unstemmed | Vaccination-induced neutralizing antibodies in immunocompetent hosts correlate with protection against rickettsiae |
| title_short | Vaccination-induced neutralizing antibodies in immunocompetent hosts correlate with protection against rickettsiae |
| title_sort | vaccination induced neutralizing antibodies in immunocompetent hosts correlate with protection against rickettsiae |
| url | https://doi.org/10.1038/s41541-025-01228-4 |
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