About Immunity

(4) Innate immunity memory: why BCG vaccination increases corona resistance?

Statistics show that the number of people infected with COVID 19 (new coronavirus in 2019) and the number of associated deaths is low in countries where the population has received Bacille Calmette Guerin (BCG) vaccinations (*1).

BCG is a vaccine for the prevention of tuberculosis. By inoculating an attenuated strain (a weakened version of the living bacteria) of Mycobacterium tuberculosis in the body, antibodies against M. tuberculosis can be produced without adverse events. But why does producing antibodies against M. tuberculosis increase resistance to COVID 19, which is unrelated to M. tuberculosis? This is because BCG not only makes antibodies against M. tuberculosis but also raises innate immunity, which provides non-specific protection against infections, whether it is M. tuberculosis, other bacteria, or a virus.

But why does childhood BCG vaccination increase resistance to COVID 19 in adulthood? This is an interesting point. In fact, it has recently become clear that there is a “memory” in the activation of innate immunity. “Memory” here means that chromatin (a structure packed with DNA) is maintained in an unfolded state so that genes related to innate immunity can be immediately activated (*2). This may be a bit difficult to understand, but DNA, which contains genetic information, is wrapped around a protein called a histone, and the histones are stored together so that they do not get entangled. This is called chromatin. However, in this packed state, the gene cannot be immediately activated. So, the “memory” is a little unfolded, which means that it is easy to read when needed.

BCG is not the only source of innate immune memory. Other substances can activate innate immunity to some extent to create innate immune memory. One of these is lipopolysaccharide (LPS) (*3, 4). LPS activates innate immunity and is memorized. The study of innate immune memory will be an area of great interest.

（*1）https://news.yahoo.co.jp/byline/kimuramasato/20200405-00171556/
（*2）BCG-induced protection: effects on innate immune memory.
Semin Immunol. 26(6):512-517 (2014)
（*3）https://www.riken.jp/press/2015/20150901_2/
（*4）The transcription factor ATF7 mediates lipopolysaccharide-induced epigenetic changes in macrophages involved in innate immunological memory.
Nature Immunology, published online 31 August (2015)