The Systems Approach

Systems biology was on the agenda today, and speakers described many projects that use this more holistic approach to study vaccination and infections. While there is a lot of promise in the approach, it also presents challenges. One challenge came up repeatedly today;  when researchers use microarrays to measure the expression of thousands of genes, the data of gene expression changes might just reflect changes in the abundance of certain cell types and not changes in gene expression in the same cell type. “This comes up again and again and again [that] you are getting these gene changes and much of what you are getting is simply the change in populations,” said Ron Germain of the National Institute of Allergy and Infectious Diseases, who mentioned the problem in his talk. 

One way to separate the gene expression data for the different cell types is to separate the cell types first and then do gene expression analyses, but this can be expensive. Bali Pulendran of Emory University discussed another solution. He used publicly available gene expression data to create libraries of genes that are typically expressed in different cell types of the immune system. 

It was also interesting to hear that researchers have not only used a systems biology approach to predict immune responses to vaccines (see A Systems Approach to Understanding Vaccines, IAVI Report, July-Aug. 2010), but also to predict adverse events to vaccines. I-Ming Wang at Merck Research Laboratories classified several marketed vaccines according to the severity of the adverse events they induce in humans (for example, local ones like swelling or systemic ones like headache) and then correlated gene expression signatures induced by these vaccines in rhesus macaques with the adverse events. He found that genes induced by type I interferon (IFN) seem to predict adverse events in response to a vaccine. 

But IFN doesn’t always have to be a bad thing: In another study, genes induced by IFN seemed to predict protection induced by a vaccine. Rafick Sékaly of the Vaccine & Gene Therapy Institute in Florida, in collaboration with Louis Picker of Oregon Health & Sciences University, vaccinated rhesus macaques with different live-attenuated vaccines, including simian immunodeficiency virus (SIV) mac239Δnef, and challenged them a year later with SIVmac251. When they checked gene expression nine days after the initial vaccination, they found that the macaques that later turned out to be best protected had a high IFN response shortly after vaccination but a low IFN response after challenge, whereas macaques that were not protected showed the opposite profile.