New clues to T cell development could boost search for HIV vaccine

Scientists around the world have spent many years trying to make effective vaccines for HIV and hepatitis C, with little success. So the only way to control these chronic viruses is with drugs.

Antiretroviral medicines effectively control HIV levels, but the slightest slip in adherence could send virus levels bouncing back. And while a number of new hep C drugs have hit the market in recent years, they tend to be pricey, with Gilead’s Sovaldi going for $1,000 per pill, or $84,000 for a 12-week course of treatment.

Now California researchers have discovered how a type of killer T cell develops, opening the door to improved vaccine design for diseases, such as HIV and hep C.

T cells are usually divided by function according to the cell surface markers CD4 and CD8. CD4-positive cells tend to be "helper" T cells, which call forth other immune cells, while CD8-positive cells are "killer" T cells, which destroy infected or cancerous cells.

The team, from La Jolla Institute for Allergy and Immunology, focused on CD4 cytotoxic T cells. CD4 killer T cells are primarily found in people with chronic viral infections, but they have also been observed to play a role in protective anti-tumor responses. While it was known that CD4 helper cells can turn into killer cells in certain conditions, this transition was poorly understood.

“The observed increase in the ratio of cytotoxic CD4 T cells to CD4 helper T cells indicates that they are an important component of the protective immune response to viral infections and that their induction should be an important marker for successful vaccinations against certain viral diseases," said postdoctoral researcher and first author Veena Patil, in a statement. "But we really didn't know enough about their molecular profile and the mechanisms that drive their differentiation and maintenance."

The findings, which identify a previously unknown precursor for this group of T cells, explain how CD4 killer T cells come to be and could help fine-tune vaccine design for the likes of HIV, hep C and cytomegalovirus.

"Understanding the origins and biology of potentially long-lived CD4-CTL [CD4 killer T cell] precursors may pave the way for developing strategies to boost durable CD4-CTL immune responses after vaccination against viral infections and cancer," the authors wrote.

Creating vaccines for HIV and hepatitis C has been challenging because both are viruses that mutate rapidly to elude the immune system. Scientists at the AIDS Vaccine Initiative and the Scripps Research Institute are focusing on viral changes and antibody features that could serve as a blueprint for an HIV vaccine design.

Meanwhile, the University of Maryland scooped up $6 million from the NIH to develop a hep C vaccine with a “structure-based design.” The idea is to create vaccine immunogens at the atomic level in order to “stabilize” the antigen and avoid the distracting elements of a quickly evolving virus.