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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Main Authors: 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
Format: Article
Language:English
Published: Nature Portfolio 2025-08-01
Series:npj Vaccines
Online Access:https://doi.org/10.1038/s41541-025-01228-4
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Summary: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.
ISSN:2059-0105