Abstract
Transcriptomic profiling of the immune response induced by vaccine adjuvants is of critical importance for the rational design of vaccination strategies. In this study, transcriptomics was employed to profile the effect of the vaccine adjuvant used for priming on the immune response following re-exposure to the vaccine antigen alone. Mice were primed with the chimeric vaccine antigen H56 of Mycobacterium tuberculosis administered alone or with the CAF01 adjuvant and boosted with the antigen alone. mRNA sequencing was performed on blood samples collected 1, 2, and 7 days after priming and after boosting. Gene expression analysis at day 2 after priming showed that the CAF01 adjuvanted vaccine induced a stronger upregulation of the innate immunity modules compared with the unadjuvanted formulation. The immunostimulant effect of the CAF01 adjuvant, used in the primary immunization, was clearly seen after a booster immunization with a low dose of antigen alone. One day after boost, we observed a strong upregulation of multiple genes in blood of mice primed with H56 + CAF01 compared with mice primed with the H56 alone. In particular, blood transcription modules related to innate immune response, such as monocyte and neutrophil recruitment, activation of antigen-presenting cells, and interferon response were activated. Seven days after boost, differential expression of innate response genes faded while a moderate differential expression of T cell activation modules was appreciable. Indeed, immunological analysis showed a higher frequency of H56-specific CD4+ T cells and germinal center B cells in draining lymph nodes, a strong H56-specific humoral response and a higher frequency of antibody-secreting cells in spleen of mice primed with H56 + CAF01. Taken together, these data indicate that the adjuvant used for priming strongly reprograms the immune response that, upon boosting, results in a stronger recall innate response essential for shaping the downstream adaptive response.
Highlights
Vaccines based on purified antigens are often poorly immunogenic and need to be formulated with adjuvants or delivery systems, to increase the amount, quality, and duration of the immune response to vaccination as well as to ensure long-lived immunological memory and protection [1]
The observed GC-B cells response is clearly a recall response of cells elicited by the primary immunization, since we have previously demonstrated that primary immunization with H56 alone does not stimulate the germinal center reaction, while the CAF01 adjuvant is a strong promoter of this reaction [4]
Transcriptomic profiling of the immune response induced by vaccine adjuvants can contribute understanding the mechanism of action of adjuvants and guide the rational design of prime-boost vaccination strategies
Summary
Vaccines based on purified antigens are often poorly immunogenic and need to be formulated with adjuvants or delivery systems, to increase the amount, quality, and duration of the immune response to vaccination as well as to ensure long-lived immunological memory and protection [1]. We have characterized the antigen-specific T and B cell responses after both parenteral and mucosal priming with vaccine formulations including different adjuvants or delivery systems, and combining heterologous prime-boost schedules, demonstrating the crucial role of both the immunization route and vaccine composition [3, 5, 10,11,12,13]. The systems biology approach was first applied to characterize the immune response elicited by the yellow fever vaccine YF-17D in humans [23] and, more recently, to a variety of other vaccines including the study of adjuvanted and non-adjuvanted influenza vaccines in adults [21] and children [22, 27]
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