Vaccines that activate immediate and less specific immune responses could help curb dangerous pandemics.

David Pejoski, Casimir de Rham, Paola Martinez-Murillo, Francesco Santoro, Floriane Auderset, Donata Medaglini, Gianni Pozzi, Maria Vono, Paul-Henri Lambert, Angela Huttner, Mariëlle C Haks, Tom H M Ottenhoff, Jean Villard, Claire-Anne Siegrist, , ,

Overview

When most people think of vaccine responses, what often comes to mind are antibodies - and possibly T cells, both being key ‘adaptive’ responses that are highly specific, long term and take weeks or months to fully establish. However, in the past few decades, vaccines have been proven to elicit impressive innate immune responses as well. These responses include activation of Natural Killer (NK) cells - amongst many other cell types, and cytokines – the chemical messengers of the immune system. Together, these cells and soluble factors can be thought of as the rapid and non-specific first line defense system of the body.

Summary

The EBOVAC / EBOPLUS consortia invested some time and effort into investigating vaccine-induced innate immune responses after surprising results from the 'ring vaccination' approach that effectively controlled the 2015 Ebolavirus epidemic in Africa. The vaccine used at the time, rVSV-ZEBOV (Merck), is now the first FDA-approved vaccine for Ebolavirus disease. Specifically, we wanted to investigate the innate responses because this vaccine clearly protected people from infection even before the adaptive immune response was fully formed, suggesting that the innate immune system could mediate beneficial clinical effects. Infectious diseases that cause pandemics require rapid development of prophylactic and therapeutic interventions. One only has to turn the internet on at the moment to be flooded with information about the latest COVID-19 vaccine or drug trials. While past vaccines have focused on disease-specific immune responses, it may be time to re-evaluate this paradigm. By developing a new class of vaccines that is intended to be used as a generic immunostimulator, we could reduce the infection rate in the face of newly emerging pathogens for which no specific treatments exist. This Pubfacts Showcase article reflects my own opinions about our open-access research paper, available here: https://doi.org/10.1038/s41541-020-0179-4

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Author Comments

David Pejoski, Ph.D.
David Pejoski, Ph.D.
University of Geneva
Maître Assistant / Postdoctoral Researcher
Immunology
Geneva | Switzerland
Technically, our findings reveal that the rVSV-ZEBOV Ebolavirus vaccine confers protection within days after immunization, suggesting the contribution of innate immune responses. We identified modulation of rVSV-ZEBOV vaccinee blood CD56+ NK cell numbers, NKG2D or NKp30 surface receptor expression, Killer Immunoglobulin-like Receptor (KIR)+ cell percentages and NK-cell-related genes on day 1 post immunization. Inverse correlations existed between the concentration of several plasma cytokines and inhibitory KIR+ CD56dim or cytokine-responsive CD56bright NK cells. Thus, NK cells may contribute to the early protective efficacy of rVSV-ZEBOV in humans, in addition to the many cytokines which have been described in previous publications. David Pejoski, Ph.D.

Resources

Free access - original research article
https://doi.org/10.1038/s41541-020-0179-4

Rapid dose-dependent Natural Killer (NK) cell modulation and cytokine responses following human rVSV-ZEBOV Ebolavirus vaccination.

NPJ Vaccines 2020 14;5:32. Epub 2020 Apr 14.

1Department of Pathology and Immunology, Faculty of Medicine, University of Geneva, Geneva, Switzerland.

The rVSV-ZEBOV Ebolavirus vaccine confers protection within days after immunization, suggesting the contribution of innate immune responses. We report modulation of rVSV-ZEBOV vaccinee blood CD56 NK cell numbers, NKG2D or NKp30 surface receptor expression, Killer Immunoglobulin-like Receptor (KIR) cell percentages and NK-cell-related genes on day 1 post immunization. Inverse correlations existed between the concentration of several plasma cytokines and inhibitory KIR CD56 or cytokine-responsive CD56 NK cells. Thus, NK cells may contribute to the early protective efficacy of rVSV-ZEBOV in humans.

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Source
http://dx.doi.org/10.1038/s41541-020-0179-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7156503PMC
April 2020

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