Mechanisms of Vaccine-Induced Protective Immunity against Coxiella burnetii Infection in BALB/c Mice

Abstract

To elucidate the mechanisms of vaccine-induced protective immunity against Coxiella burnetii infection, we compared the protective efficacy and immunogenicity between formalin-inactivated phase I vaccine (PI-V) and phase II vaccine (PII-V) in BALB/c mice. PI-V generated significant protection while PII-V did not confer measurable protection. Analysis of cytokine and subclass Ab responses indicated that both PI-V and PII-V were able to induce a Th1-dominant immune response but did not identify the component of host response that distinguished their ability to induce protective immunity. Interestingly, immunoblot analysis identified a difference between PI-V and PII-V vaccinates in antigenic recognition by specific Ab isotypes. The observation that PI-LPS elicited significant protection but PII-LPS did not confer measurable protection suggests PI-LPS may play a key role in PI-V-induced protection. Adoptive transfer of either immune sera or splenocytes mediated significant protection in naive BALB/c mice, supporting the notion that both humoral and cellular immunity are important for development of protective immunity. However, the evidence that immune sera and B cells were unable to control infection while T cells conferred significant protection in SCID mice supports the hypothesis that T cell-mediated immunity is critical for host defense against C. burnetii infection. This report presents novel evidence to highlight the importance of PI-LPS and Abs in protective immunity and has important implications for the design of new generation vaccines against Q fever.

Role of CD4+and CD8+T Cells in Clearance of Primary Pulmonary Infection withCoxiella burnetii

“…Adoptive transfer of sera from immunized mice also conferred protection against a subsequent i.p. NMI infection (25). Collectively, the data presented here indicate that B cells are not required for resolving primary NMI lung infections as SCID mice reconstituted with only T cells, in the absence of B cells, were able to control infections as well as mice reconstituted with both T cells and B cells.…”

Coxiella burnetii immunogenic proteins as a basis for new Q fever diagnostic and vaccine development

“…Also, a cellular immune response contributes to protective immunity. Adoptive transfer of CD8+ and CD4+ T cells conferred measurable protection against C. burnetii challenge (Xiong et al, , 2016Zhang et al, 2007). C. burnetii causes death in the SCID and T cell deficient mice, but not in B cell deficient mice.…”

“…For an effective immunity against C. burnetii, both the humoral and cellular immune response, and especially their interplay with CD4+ T cells are needed (Zhang et al, 2004b andAndoh et al, 2007;Chen et al, 2011). Naïve mice that received serum from vaccinated mice were protected against C. burnetii challenge as stated by Vigil et al (2011).…”

“…C. burnetii causes death in the SCID and T cell deficient mice, but not in B cell deficient mice. Therefore, T cells seem to be essential for Q fever immunity (Andoh et al, 2007).…”

Coxiella burnetii, agent de la fièvre Q

“…Les vaccins composés d'antigènes corpusculaires de phase I sont les seuls efficaces (Zhang et al 2007). L'excrétion bactérienne dans le placenta et le lait a été réduite chez des chèvres, des moutons ou des vaches inoculés avec des vaccins phase I, puis infectés, naturellement ou expérimentalement Guatteo et al 2008).…”