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 .

Soluble antigens derived from Coxiella burnetii elicit protective immunity in three animal models without inducing hypersensitivity

“…Both CpG and QuilA were found to be strong Th1 polarizing adjuvants, as indicated by the IgG2c skewed response, which has been suggested to be an important correlate of protective immunity against Q fever. 15,50,56 Further analysis of serological responses to Sol II revealed a dose-dependent correlation with an increasing IgG2c ratio. Increasing the number of doses or administering a higher dose also resulted in the development of high avidity polyclonal serum, indicating affinity maturation.…”

“…Previous studies have indicated Th1 immune responses are an important correlate of protective immunity against Q fever. 15 , 50 , 51 For this reason, CpG was selected as the adjuvant of choice for all future Sol II immunizations.…”

The Route of Vaccine Administration Determines Whether Blood Neutrophils Undergo Long-Term Phenotypic Modifications

“…High-dimensional cytometry, including mass cytometry and spectral flow cytometry, is a powerful technique to monitor immunity, identify cell subsets associated with diseases or potent responses to vaccines, and decipher the complex mechanisms of the immune response to vaccines (20)(21)(22)(23)(24)(25)(26)(27). However, the comparison and integration of different datasets generated at multiple sites and on different days is challenging, even when using the same technology.…”

Strategies for Immunomonitoring after Vaccination and during Infection

“…These highly multiparametric methods require bioinformatic expertise, allowing unsupervised analysis [86], with the advantage of automatically defining cell subsets that might been not highlighted with conventional supervised analysis, in addition to getting rid of operatordriven analysis bias. This may lead to the identification of novel cell populations that could be associated with an effective vaccine response [87,88].…”