<p>We previously demonstrated that a single-dose immunization with a live-attenuated <i>Rickettsia parkeri</i> 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<sup>+</sup> CD45R<sup>+</sup> IgD<sup>low</sup> plasma cells. Compared to mock controls, passive transfer of immune sera from 3A2-immunized mice protected C3H-SCID mice from <i>R. parkeri</i> 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 <i>R. parkeri</i> 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.</p>

错误:搜索内容不能为空,请输入英文关键词
错误:关键词超出字数限制,请精简
高级检索

Vaccination-induced neutralizing antibodies in immunocompetent hosts correlate with protection against rickettsiae

  • 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

摘要

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.