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Novel multiparameter correlates of Coxiella burnetii infection and vaccination identified by longitudinal deep immune profiling.

ABSTRACT: Q-fever is a flu-like illness caused by Coxiella burnetii (Cb), a highly infectious intracellular bacterium. There is an unmet need for a safe and effective vaccine for Q-fever. Correlates of immune protection to Cb infection are limited. We proposed that analysis by longitudinal high dimensional immune (HDI) profiling using mass cytometry combined with other measures of vaccination and protection could be used to identify novel correlates of effective vaccination and control of Cb infection. Using a vaccine-challenge model in HLA-DR transgenic mice, we demonstrated significant alterations in circulating T-cell and innate immune populations that distinguished vaccinated from naïve mice within 10 days, and persisted until at least 35 days post-vaccination. Following challenge, vaccinated mice exhibited reduced bacterial burden and splenomegaly, along with distinct effector T-cell and monocyte profiles. Correlation of HDI data to serological and pathological measurements was performed. Our data indicate a Th1-biased response to Cb, consistent with previous reports, and identify Ly6C, CD73, and T-bet expression in T-cell, NK-cell, and monocytic populations as distinguishing features between vaccinated and naïve mice. This study refines the understanding of the integrated immune response to Cb vaccine and challenge, which can inform the assessment of candidate vaccines for Cb.

SUBMITTER: Reeves PM

PROVIDER: S-EPMC7414860 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature

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Novel multiparameter correlates of Coxiella burnetii infection and vaccination identified by longitudinal deep immune profiling.

Reeves P M PM Raju Paul S S Baeten L L Korek S E SE Yi Y Y Hess J J Sobell D D Scholzen A A Garritsen A A De Groot A S AS Moise L L Brauns T T Bowen R R Sluder A E AE Poznansky M C MC

Scientific reports 20200807 1

Q-fever is a flu-like illness caused by Coxiella burnetii (Cb), a highly infectious intracellular bacterium. There is an unmet need for a safe and effective vaccine for Q-fever. Correlates of immune protection to Cb infection are limited. We proposed that analysis by longitudinal high dimensional immune (HDI) profiling using mass cytometry combined with other measures of vaccination and protection could be used to identify novel correlates of effective vaccination and control of Cb infection. Us ...[more]

PMID: 32770104

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Project description:IntroductionSheep are considered to be one of the main reservoirs for Coxiella burnetii, a gram-negative bacterium with high zoonotic potential. Infected sheep shed tremendous amounts of the pathogen through birth products which caused human Q fever epidemics in several countries. Information about the impact of an inactivated C. burnetii Phase I vaccine on humoral immune response, vaginal shedding, and lamb mortality in naturally pre-infected sheep is scarce.MethodsTwo identically managed and naturally C. burnetii-infected sheep flocks were examined for two lambing seasons (2019 and 2020). One flock (VAC) received a primary vaccination against Q fever before mating and the second flock served as control (CTR). In each flock, one cohort of 100 ewes was included in follow-up investigations. Serum samples at eight different sampling dates were analyzed by C. burnetii phase-specific ELISAs to differentiate between the IgG Phase I and II responses. Vaginal swabs were collected within three days after parturition and examined by a C. burnetii real-time PCR (IS1111). Lamb losses were recorded to calculate lamb mortality parameters.ResultsAfter primary vaccination, almost all animals from cohort VAC showed a high IgG Phase I response up until the end of the study period. In cohort CTR, the seropositivity rate varied from 35.1% to 66.3%, and the Phase I and Phase II pattern showed an undulating trend with higher IgG Phase II activity during both lambing seasons. The number of vaginal shedders was significantly reduced in cohort VAC compared to cohort CTR during the lambing season in 2019 (p < 0.0167). There was no significant difference of vaginal shedders in 2020. The total lamb losses were low in both cohorts during the two investigated lambing seasons (VAC 2019: 6.8%, 2020: 3.2%; CTR 2019: 1.4%, 2020: 2.7%).DiscussionNeither the C. burnetii vaccine nor the C. burnetii infection seem to have an impact on lamb mortality. Taken together, the inactivated C. burnetii Phase I vaccine induced a strong IgG Phase I antibody response in naturally pre-infected sheep. It might also reduce vaginal shedding in the short term but seems to have little beneficial impact on lamb mortality.

Dataset Information

Novel multiparameter correlates of Coxiella burnetii infection and vaccination identified by longitudinal deep immune profiling.

Publications

Novel multiparameter correlates of Coxiella burnetii infection and vaccination identified by longitudinal deep immune profiling.

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