Immune response to flu more complex than previously thought, say CHOP scientists

New findings from researchers at the Children’s Hospital of Philadelphia could re-write immunology textbooks and change how scientists design vaccines.

At least for making antibodies, it’s been assumed that killed viruses, which are often used in vaccines, work pretty much just as well as their live counterparts.

“But I think what our research says is that that’s not necessarily the case,” said CHOP viral immunologist Laurence Eisenlohr, who until recently was a professor at Thomas Jefferson University.

Eisenlohr’s team studied influenza infection in mice and found that killed virus wasn’t processed the same way as live virus.

“The cellular processes that are involved in generating these targets from live virus are different,” said Eisenlohr. “They’re broader; they’re more varied than those processes that are brought to bear against the killed virus.”

T cells detect viruses after they’ve been cut up into tiny bits and deposited on the outside of cells with a special protein. Helper T cells, which spew out factors that amp up killer T cells and aid B cells in making antibodies, have long been thought to respond primarily to viral pieces that have been picked up from outside cells. But according to the new work, those fragments come from inside infected cells.

“When we first got these results, we were shocked,” said Eisenlohr. “In fact, I did not believe them.”

It will be important to see if the finding holds up in humans and with other viruses, Eisenlohr said, but since it’s fundamental biology, he suspects it will. The work was published in the journal Nature Medicine.

The discovery suggests that to make better vaccines, researchers will need to come up with creative ways of more closely mimicking infection, essentially tricking cells into doing the more varied processing that occurs naturally with a real microbe.

This new knowledge of how T cells become activated, Eisenlohr added, could also help scientists better understand autoimmune disorders and figure out new approaches to attacking tumors.