Wednesday, December 23, 2015

DNA vaccine immunogenicity requires STING but not cGAS activity

Intracellular DNA sensor STING has become a major player in mediating the range of immune responses from viruses to tumors to autoimmunity.

From practical point of view, a therapeutic application of STING pathway would involve development of DNA vaccines both for infectious diseases or cancers. In general, DNA vaccine has a long history of testing, but if I am not mistaken there is still no FDA-approved human DNA vaccine [though I think there is approved DNA vaccines for domestic animals].  

So it was interested to read this new paper in Journal of Immunology where the authors found that priming of adaptive immune response by DNA vaccine expressing Flu virus H1 antigen required STING but surprisingly not cGAS pathway.

This is a simple paper. First, the authors found that two i.m injections of H1HA DNA vaccine could prime anti-Flu H1-specific CD8 T cell and IgG response in WT but not in STING KO mice.

However, surprisingly, cGAS KO mice that are deficient of enzyme upstream of STING pathway showed normal response to this DNA vaccine.

Finally, mice deficient for IRF7, but not IRF3, showed similar [to STING KO] reduction of DNA vaccine-induced adaptive immune response (earlier this year journal Science has published research article describing IRF7 deficient patient who showed severe susceptibility to H1N1 viral infection).

In summary, this paper showed that DNA vaccine immunogenicity required STING/IRF7 pathway rather than classical cGAS/STING/IRF3 pathway.

Of note, since the authors have not done virus challenge experiment, the results in this study do not necessarily tell whether this DNA vaccine was effective in providing clinically relevant protection against Flu virus [one of the reasons this study was published in Journal of Immunology and not in a more prestigious journal, in my opinion].

David Usharauli

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