Tuesday, January 5, 2016

Systems vaccinology is anything but useful

Systems vaccinology is a field of immunology that tries to apply "big data" analysis to predict vaccine efficacy based on responder/non-responder signature. These signatures involve readouts such as mRNA or cytokine signature. Notwithstanding its purpose and scientific justification, systems vaccinology generated very little useful information thus far.

This week Nature Immunology has published another such paper. However, as previously, when it comes to predictions of vaccine efficacy, this new paper also concluded that "in sum, neither molecular nor cellular data offered any consensus prevaccination predictor of nonresponsiveness akin to those proposed in studies of nonadjuvanted vaccines".

I will only discuss those few data that were interesting. In this paper the authors has analysed PMBC and serum response from individuals vaccinated with adjuvanted 2009 H1N1 vaccine, Pandemrix (Of note, this is the same vaccine that caused spike in autoimmune sleeping disorder called narcolepsy in vaccinated individuals in EU). 

20% of vaccinated individuals were classified as non-responders (<4-fold increase in HAI titres)

However, no "signature" was found that correlated with vaccination outcome. Interestingly, the majority of non-responders actually had high levels of preexisting HAI titres, suggesting cross-reactivity with previous flu infection/immunization.

Since data generated by these analyses failed to provide any signature that could have predicted vaccine efficacy, the authors tried to salvage the data by analyzing signature for vaccine "side effects" also known as adverse events. This analysis revealed a correlation between number of "transitional" B cells (and high level of pre-vaccination titres of auto-antibodies) and severity of adverse events. 

What can we conclude from this "big data" study: nothing much (very close what the authors themselves said). No cytokine(s) or gene(s) expression pattern showed any correlation with vaccine efficacy. There was some unusual correlation between high level of pre-vaccination auto-antibodies and vaccine adverse events. However, this observation would require confirmation in other studies with other vaccines since this particular vaccine, Pandemrix, showed unusual tendency to induce narcolepsy, an autoimmune disease. This particular effect could have skewed their analysis.  

Overall, the results from systems vaccinology studies suggest need to develop alternative readouts, beyond PBMCs and serum cytokines, that would have more predictive powers. 

David Usharauli  

No comments:

Post a Comment