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Reverse Vaccinology

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Front. Immunol. | doi: 10.3389/fimmu.2018.02936

Trained immunity-based vaccines: a new paradigm for the development of broad-spectrum anti-infectious formulations

  • 1Facultad de Medicina, Universidad Complutense de Madrid, Spain
  • 2Inmunotek alergia e inmunología, Spain
  • 3Department of Internal Medicine, Radboud University Medical Center, Netherlands
  • 4Centro Nacional de Investigaciones Cardiovasculares (CNIC), Spain
  • 5Complutense University of Madrid, Spain

Challenge with specific microbial stimuli induces long lasting epigenetic changes in innate immune cells that result in their enhanced response to a second challenge by the same or unrelated microbial insult, a process referred to as trained immunity. This opens a new avenue in vaccinology to develop Trained Immunity-based Vaccines (TIbV), defined as vaccine formulations that induce training in innate immune cells. Unlike conventional vaccines, which are aimed to elicit only specific responses to vaccine-related antigens, TIbV aim to stimulate broader responses. As trained immunity is generally triggered by pattern recognition receptors (PRRs), TIbV should be formulated with microbial structures containing suitable PRR-ligands. The TIbV concept we describe here may be used for the development of vaccines focused to promote host resistance against a wide spectrum of pathogens. Under the umbrella of trained immunity, a broad protection can be achieved by: i) increasing the nonspecific effector response of innate immune cells (e.g. monocyte/macrophages) to pathogens, ii) harnessing the activation state of dendritic cells to enhance adaptive T cell responses to both specific and nonrelated (bystander) antigens. This capacity of TIbV to promote responses beyond their nominal antigens may be particularly useful when conventional vaccines are not available or when multiple coinfections and/or recurrent infections arise in susceptible individuals. As the set of PRR-ligands chosen is essential not only for stimulating trained immunity but also to drive adaptive immunity, the precise design of TIbV will improve with the knowledge on the functional relationship among the different PRRs. While the TIbV concept is emerging, a number of the current anti-infectious vaccines, immunostimulants and even vaccine adjuvants may already fall in the TIbV category. This may apply to increase immunogenicity of novel vaccine design approaches based on small molecules, like those achieved by reverse vaccinology.

Keywords: adjuvants, innate immunity, immunostimulants, Pattern recognition receptors (PRRs), PRR-ligands, trained immunity, Trained immunity-based vaccines (TIVs), Vaccines

Received: 04 Sep 2018; Accepted: 29 Nov 2018.

Edited by:

Pedro A. Reche, Complutense University of Madrid, Spain

Reviewed by:

Michael Schotsaert, Icahn School of Medicine at Mount Sinai, United States
Randy A. Albrecht, Icahn School of Medicine at Mount Sinai, United States  

Copyright: © 2018 Sánchez-Ramón, Conejero, Netea, Sancho, Palomares and Subiza. 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(s) 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: Dr. Silvia Sánchez-Ramón, Facultad de Medicina, Universidad Complutense de Madrid, Madrid, Spain,