Opposite effects of Vaccinia and modified Vaccinia Ankara on trained immunity

Collection Location Koleksi E-book & E-Journal Perpustakaan Pusat Unila
Edition Vol. 38, Issue 3
Call Number
ISBN/ISSN 1435-4373
Author(s) Blok, Bastiaan A...[et al.]
Subject(s) Biomedicine
Classification NONE
Series Title
GMD E-Journal
Language English
Publisher Springer
Publishing Year 2019
Publishing Place Switzerland
Abstract/Notes Abstract
Vaccines such as Vaccinia or BCG have non-specific effects conferring protection against other diseases than their target
infection, which are likely partly mediated through induction of innate immune memory (trained immunity). MVA85A, a
recombinant strain of modified Vaccinia Ankara (MVA), has been suggested as an alternative vaccine against tuberculosis, but
its capacity to induce positive or negative non-specific immune effects has not been studied. This study assesseswhether Vaccinia
and MVA are able to induce trained innate immunity in monocytes. Human primary monocytes were primed in an in vitro model
with Vaccinia or MVA for 1 day, after which the stimulus was washed off and the cells were rechallenged with unrelated
microbial ligands after 1 week. Heterologous cytokine responses were assessed and the capacity of MVA to induce epigenetic
changes at the level of cytokine genes was investigated using chromatin immunoprecipitation and pharmacological inhibitors.
Monocytes trained with Vaccinia showed significantly increased IL-6 and TNF-α production to stimulation with non-related
stimuli, compared to non-trained monocytes. In contrast, monocytes primed with MVA showed significant decreased heterologous
IL-6 and TNF-α responses, an effect which was abrogated by the addition of a histone methyltransferase inhibitor. No
effects on H3K4me3 were observed after priming with MVA. It can be thus concluded that Vaccinia induces trained immunity
in vitro, whereas MVA induces innate immune tolerance. This suggests the induction of trained immunity as an immunological
mechanism involved in the non-specific effects of Vaccinia vaccination and points to a possible explanation for the lack of effect
of MVA85A against tuberculosis.
Keywords Trained immunity . Vaccinia . Modified Vaccinia Ankara . Heterologous effects
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