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.
Highlights
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All doses of phase I vaccine (PI-V) protected mice from development of significant splenomegaly ( p Ͻ 0.05 with unvaccinated control), while all doses of phase II vaccine (PII-V)-vaccinated mice developed levels of severe splenomegaly similar to unvaccinated mice ( p Ͼ 0.05). These results suggest that PI-V was able to elicit significant protection from the development of clinical signs and splenomegaly against challenge, while PII-V did not confer measurable protection regardless of vaccination dose
The BALB/c mouse strain is intermediately sensitive to lethal challenge and has been used to estimate protective efficacy of C. burnetii Ags by several research groups (39 – 41)
Summary
PI, phase I; PII, phase II; PI-V, phase I vaccine; PII-V, phase II vaccine; NMI, Nine Mile phase I; NMII, Nine Mile phase II. Studies suggested that both humoral and cell-mediated immune responses are important for host defense against C. burnetii infection, while cell-mediated immunity probably plays the critical role in eliminating the organisms. Several in vitro studies indicated that treatment of C. burnetii with immune sera made the organisms more susceptible to phagocytosis and to destruction by normal polymorphonuclear leukocytes or macrophages [23,24,25] These studies provided strong support for the notion that humoral immunity is important in the development of the acquired resistance to C. burnetii infection. We tested whether immune sera, splenocytes, B cells, and T cells from PI-V-vaccinated mice can protect SCID mice against C. burnetii infection This is the first report to clearly show that Ab plays an important role in vaccine-induced protective immunity against C. burnetii infection
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