Transcriptomics of the Vaccine Immune Response: Priming With Adjuvant Modulates Recall Innate Responses After Boosting

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.

Role of the Microbiota in the Modulation of Vaccine Immune Responses

“…Nucleic acid sequencing enables a very broad approach to immunoglobulin or TCR repertoire analysis, allowing the determination of the diversity and clonal expansion of lymphocytes responding to vaccine (Galson et al, 2014; VanDuijn et al, 2017). The NGS methodology has become a core technology in vaccine analysis (Dhiman et al, 2009; Santoro et al, 2018) and, integrated with immunological results, has been used to profile the human response to different vaccines. This integrating approach is called “systems biology” and can be used to analyze multiple data types related to complex biological interactions by using computational analysis and mathematical modeling and to predict vaccine protection and immunogenicity (Querec et al, 2009; Li et al, 2014; Nakaya et al, 2016; Kazmin et al, 2017; van den Berg et al, 2017).…”

Computational Analysis of Multiparametric Flow Cytometric Data to Dissect B Cell Subsets in Vaccine Studies

“…Moreover, activation of B cells leads to the generation of subtypes of cells with different functions, such as plasmablasts, short‐or long‐lived plasma cells (PCs), memory cells . The presence of the adjuvant, especially in the primary immunization, allows to enhance and modulate the immune responses to vaccination and ensures the induction of long‐lived immunological memory necessary for protection .…”

Recombinant Haemagglutinin Derived From the Ciliated Protozoan Tetrahymena thermophila Is Protective Against Influenza Infection

“…The A/Cal-specific and B/Bri-specific serum IgG were evaluated by enzyme-linked immunosorbent assay (ELISA) as previously described (31). Briefly, MaxiSorp microtiter plates (Nunc) were coated with recombinant A/Cal- and B/Bri- (2 μg/ml; Cilian as described above) overnight at 4°C, blocked with PBS and 1% BSA, and then added with serum samples titrated in two-fold dilutions.…”