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Front. Immunol. | doi: 10.3389/fimmu.2018.00380

Heterologous prime-boost combinations highlight the crucial role of adjuvant in priming the immune system

  • 1Department of Medical Biotechnology, University of Siena, Italy
  • 2Department of Medical Biotechnology, University of Siena, Italy
  • 3Department of Infectious Disease Immunology, State Serum Institute (SSI), Denmark

The induction and modulation of the immune response to vaccination can be rationally designed by combining different vaccine formulations for priming and boosting. Here, we investigated the impact of heterologous prime-boost approaches on the vaccine-specific cellular and humoral responses specific for a mycobacterial vaccine antigen. C57BL/6 mice were primed with the chimeric vaccine antigen H56 administered alone or with the CAF01 adjuvant, and boosted with H56 alone, or combined with CAF01 or with the squalene-based oil-in-water emulsion (o/w Squalene) adjuvant. A strong secondary H56-specific CD4+ T cell response was recalled by all the booster vaccine formulations when mice had been primed with H56 and CAF01, but not with H56 alone. The polyfunctional nature of T helper cells was analysed and visualized with the multidimensional flow cytometry FlowSOM software, implemented as a package of the R environment. A similar cytokine profile was detected in groups primed with H56 + CAF01 and boosted with or without adjuvant, except for some clusters of cells expressing high level of IL-17 together with TNF-α, IL-2 and IFN-γ, that were significantly up-regulated only in groups boosted with the adjuvants. On the contrary, the comparison between groups primed with or without the adjuvant, showed a completely different clusterization of cells, strengthening the impact of the formulation used for primary immunization on the profiling of responding cells. The presence of the CAF01 adjuvant in the priming formulation deeply affected also the secondary humoral response, especially in groups boosted with H56 alone or o/w squalene.
In conclusion, the presence of CAF01 adjuvant in the primary immunization is crucial for promoting a primary T and B cell response that can be efficiently reactivated by booster immunization also performed with antigen alone; the presence of the adjuvant in the booster formulation can be useful for modulating the secondary response of functional T cells expressing specific pattern of cytokines.

Keywords: prime-boost regimens, adjuvants, computational flow cytometry, T cells, Intracellular cytokines, CAF01, priming

Received: 30 Nov 2017; Accepted: 12 Feb 2018.

Edited by:

Fabio Bagnoli, GlaxoSmithKline (Italy), Italy

Reviewed by:

Arun Kumar, Linköping University, Sweden
Evelina Angov, Walter Reed Army Institute of Research, United States  

Copyright: © 2018 Ciabattini, Pettini, Fiorino, Lucchesi, Pastore, Brunetti, Santoro, Andersen, Bracci, Pozzi and Medaglini. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: PhD. Annalisa Ciabattini, University of Siena, Department of Medical Biotechnology, Siena, Italy,